CN106138248A - A kind of giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds and application thereof - Google Patents
A kind of giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds and application thereof Download PDFInfo
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
- A61K36/704—Polygonum, e.g. knotweed
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- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
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Abstract
The purpose of the present invention is just to provide a kind of giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds and application thereof, can effectively solve to treat the medication problem of early diabetic nephropathy.The technical scheme that the present invention solves is, this giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds are by mass ratio meter: giant knotweed rhizome general anthraquinone: arasaponin=1 1.5:1 1.5.Said composition is effective to treat early diabetic nephropathy and realizes application in preparation treatment early diabetes medicine for the composition.Instant component is simple, it is easy to producing, taking convenience, effect is good, is effective to the medication problem to early diabetes treatment, is that on medicine innovates greatly, and economic and social benefit is notable.
Description
Technical field
The present invention relates to medicine, particularly a kind of giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds and application thereof.
Background technology
Diabetic nephropathy (diabetic nephropathy, DN) be the common chronic microvascular complication of diabetes it
One, it is the specific Damages to kidney for the diabetes (diabetesmellitus, DM), it threatens the life of patient, affects
Patient and the quality of life of household, and worldwide diabetic nephropathy has become the underlying cause of death of diabetic.At present,
To radical cure diabetic nephropathy, we still lack ideal medicament.Thus improve patient vitals's quality of life.From the point of view of traditional Chinese medical science angle, the stasis of blood
Blood is the Etiological that diabetic nephropathy occurs conversion.Hemostasis is the pathological product of diabetes, is again that diabetic complication is sent out
Sick reason.Blood stasis runs through diabetic nephropathy all the time, because the traditional Chinese medical science is particular about " etiological treatment ", therefore, wants to stop or delay
Glycosuria generation renal complications or to having occurred that diabetic nephropathy delays it to be developed to ESRD (end-
Stagerenaldisease, ESRD), reach the purpose of " both disease was preapred for an unfavorable turn of events ", be necessary for using blood-activating stasis-removing kind medicine to diabetes
Ephrosis carries out early treatment, thus improves Diabetic Nephropathy patients life, quality of life, reduces medical waste.
Polygonum cuspidatum Sieb. et Zucc derives from root and the stem of polygonaceae plant giant knotweed (Polygonum cuspidatum Siebet Zucc),
Have promoting blood circulation and removing blood stasis, the effect such as clearing heat and detoxicating.In recent years, giant knotweed is usually used in the preventing and treating of DN clinically, again because of diabetic nephropathy
It is feature with " empty for this, scorching for mark ", " multiple deficiency and stasis ", so giant knotweed is many clinically and the inrigorating qi and promoting blood circulation such as the Radix Astragali, motherwort
Medicine compatibility is applied.Pharmacological research shows, giant knotweed active ingredient has antiviral, antibacterial, anti-inflammatory, anti-oxidant, suppression platelet aggregation
The effect such as collection and diuresis, is therefore widely used in clinic.And in modern medicine study, show that giant knotweed rhizome general anthraquinone can pass through
The kidney to diabetic nephropathy for the number of ways is protected.As reduced Urine proteins, microdose urine protein, reduce urea nitrogen, creatinine
Generation etc..
Meanwhile, pseudo-ginseng also has a lot of application as the representative Chinese medicine of blood-activating drug in the treatment of diabetic nephropathy.A lot of literary compositions
Offer confirmation arasaponin and there is reducing blood lipid, improve atherosclerotic, the renal cells of suppression Uremic serum induction
Propagation and the secretion of total collagen, thus delay renal tubulointerstitial progression of fibrosis, improve renal function.It is total that research is also show that pseudo-ginseng
Saponin(e can reduce platelet aggregation, improves blood viscosity, expands renal blood vessels, improves microcirculation.Because arasaponin has
There is multiple biologically active, not only greatly developed at treating cardiac and cerebral vascular diseases, and be widely used in the research of diabetic nephropathy
And treatment.Even if without the performance of obvious stasis syndrome on disease, tongue, arteries and veins, but during glomerulosclerosis and kidney region fibrosis,
The change of the denaturation of hemorheology, the clotting mechanism of immune response mediation and lipometabolic disorder and Renal Paphology is all blood
The performance of the stasis of blood.
Although giant knotweed rhizome general anthraquinone and arasaponin belong to drug for invigorating blood circulation and eliminating stasis, but its limited use, and using effect is simultaneously
Unsatisfactory, then can the composition that giant knotweed rhizome general anthraquinone and arasaponin be combined composition be used for treating getting up early sugar
The sick ephrosis of urine is so far there are no open report.
Content of the invention
For above-mentioned situation, for overcoming the defect of prior art, the purpose of the present invention is just to provide a kind of giant knotweed rhizome general anthraquinone
With notoginseng total saponin compounds and application thereof, can effectively solve to treat the medication problem of early diabetic nephropathy.
The technical scheme that the present invention solves is, this giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds are by mass ratio meter:
Giant knotweed rhizome general anthraquinone: arasaponin=1-1.5:1-1.5.Said composition is effective to treatment early diabetic nephropathy and realizes combination
Application in preparation treatment early diabetes medicine for the thing.
Instant component is simple, it is easy to producing, taking convenience, effect is good, is effective to the use to early diabetes treatment
Medicine problem, is that on medicine innovates greatly, and economic and social benefit is notable.
Brief description
Fig. 1 is giant knotweed rhizome general anthraquinone of the present invention impact on rat body weight with arasaponin and proportioning application thereof；
Fig. 2 is giant knotweed rhizome general anthraquinone of the present invention impact on rat body weight with arasaponin and different ratio application thereof；
What Fig. 3 was the present invention on rat urine albumen and microdose urine protein affects figure；
What Fig. 4 was the present invention on DN rat urine albumen and microdose urine protein affects figure；
Fig. 5 is that the present invention affects figure to rat urea nitrogen renal function；
Fig. 6 is that the present invention affects figure to rat serum creatinine renal function；
Fig. 7 is that the present invention affects figure to rat kidney；
Fig. 8 is that the present invention affects figure to rat TC, TG, HDL-C, LDL-C；
Fig. 9 is the content expression figure to renal tissues of rats TGF-β 1 for the present invention；
Figure 10 is the expression figure to AGEs in renal tissues of rats for the present invention；
Figure 11 is the expression figure to RAGE in renal tissues of rats for the present invention；
Figure 12 is the expression figure to FN in renal tissues of rats for the present invention；
Figure 13 is the expression figure to Smad3a in renal tissues of rats for the present invention.
Detailed description of the invention
Below in conjunction with embodiment and concrete condition, the detailed description of the invention to the present invention elaborates,
The present invention can be given by following example in being embodied as:
Embodiment 1: the composition alleged by the present invention is the composition of giant knotweed rhizome general anthraquinone and arasaponin, giant knotweed rhizome general anthraquinone
It is 1:1 with arasaponin mass ratio.
Embodiment 2: the composition alleged by the present invention is the composition of giant knotweed rhizome general anthraquinone and arasaponin, giant knotweed rhizome general anthraquinone
It is 1.5:1 with arasaponin mass ratio.
Embodiment 3: the composition alleged by the present invention is the composition of giant knotweed rhizome general anthraquinone and arasaponin, giant knotweed rhizome general anthraquinone
It is 1:1.5 with arasaponin mass ratio.
The giant knotweed rhizome general anthraquinone that embodiment 1 and embodiment 3 are given and notoginseng total saponin compounds are effective to treatment early sugar futures
The sick ephrosis of urine, it is achieved the application in preparation, treatment early diabetic nephropathy medicine, described giant knotweed rhizome general anthraquinone is total with pseudo-ginseng
Saponin(e is commercially available prod (existing product).
The present composition achieves, through site test, the Advantageous Effects being satisfied with very much, and relevant testing data is as follows:
(1), materials and methods
1st, material
1.1st, medicinal material
Giant knotweed rhizome general anthraquinone, lot number: ZL140215869 content: 50% is provided by Nanjing Zelang Pharmaceutical Technology Inc..
Arasaponin, lot number: DR20131106 content: 80% is provided by Shanghai Li Ding Bioisystech Co., Ltd.Beautiful
Spring ball, lot number: 140302 specifications: 60 grams/box Jiuzhitang Jinding Pharmaceutical Co., Ltd., Chengdu produces.
1.2nd, reagent
Streptozotocin (STZ), sigma company of the U.S. produces, article No.: S01300, and universal love port, Beijing commerce trading center provides；
Physiological saline, Henan Shuan Hehuali pharmaceutcal corporation, Ltd, lot number: 1410045B；
Triglycerides (TG) kit, Nanjing builds up Bioengineering Research Institute, lot number: 20150203；
T-CHOL (T--CHO) kit, Nanjing builds up Bioengineering Research Institute, lot number: 20150204；
LDL-C (LDL-C) kit, Nanjing builds up Bioengineering Research Institute, lot number: 20150209；
HDL-C (HDL-C) kit, Nanjing builds up Bioengineering Research Institute, lot number: 20150204；
Rat (Rat) microdose urine protein Elisa kit, Chinese Research Institute of Atomic Energy Sciences's offer lot number:
20150102B；
Total urinary protein kit, Nanjing builds up Bioengineering Research Institute, lot number: 20150115；
Urea nitrogen (BUN) kit, Nanjing builds up Bioengineering Research Institute, lot number: 20150205；
Creatinine (Cr) kit (enzymic creatinine assay method), Nanjing builds up Bioengineering Research Institute, lot number: 20150206；
Rabbit anti-rat AGEs polyclonal antibody (bs-1158R), specification: 0.2ml/ props up, Beijing Bo Aosen biotechnology is limited
Company produces；
Rabbit anti-rat RAGE polyclonal antibody (bs-0177R), specification: 0.2ml/ props up, Beijing Bo Aosen biotechnology is limited
Company produces；
Rabbit anti-rat TGF-β 1 polyclonal antibody (bs-0103R), specification: 0.2ml/ props up, Beijing Bo Aosen biotechnology has
Limit company produces；
Rabbit anti-rat Smad3 (bs-3484R) polyclonal antibody, specification: 0.2ml/ props up, Beijing Bo Aosen biotechnology has
Limit company produces；
Rabbit anti-rat FN (bs-4859R) polyclonal antibody, specification: 0.2ml/ props up, the limited public affairs of Beijing Bo Aosen biotechnology
Department produces；
Two resist: SP Kit (Broad Spectrum) wide spectrum SP immunologic combined detection reagent kit (SP-0022) specification:
0.2ml/ props up, and Beijing Bo Aosen Bioisystech Co., Ltd produces；
DAB colour reagent box, Fuzhou Maixin biotechnology Development Co., Ltd.
1.3rd, instrument
Centrifuge, Beijing Medical Instruments repair shop；
Ultra low temperature freezer, SANYO produces；
Electronic balance, LT2002E, sky, Changshu City measuring appratus Co., Ltd 2000/0.01g；
Adjustable pipette, Shanghai Lei Bo Analytical Instrument Co., Ltd；
UV-2000 spectrophotometer, UNICO(Shanghai) Instruments Co., Ltd.；
Biotek ELIASA, Epoch, Bai Teng Instrument Ltd. of the U.S.；
Tissue processor, EX45521303, Thermo SCIENTIFIC；；
Instrument, Changzhou Texlab Electronic Instrument Co., Ltd. are dried in pathological tissue drift；
Slicer, MiSCrom HM325, Thermo SCIENTIFIC；
Overflow dyeing machine, HIS80S30Y, Thermo SCIENTIFIC；
Light microscope BX-61, OLYMPUS (Olympus) company of Japan；
Electric heating constant-temperature water-bath tank DHG-9031, Shanghai produces；
1.4th, animal and feed
SD rat, male, body weight: 180～200g；There is provided by Shandong Province's Experimental Animal Center, credit number: SCXK Shandong
20130001；
Feed, cleaning grade, provided by Henan Province's Experimental Animal Center, credit number: SCXK (Henan 2010-0002)；
1.5th, 0.1M citric acid-sodium citrate buffer solution (pH4.3) compound method
1. citric acid (C is accurately weighed6H8O7·H2O) 2.1g, adds distilled water to 100ml, is made into solution A；
2. sodium citrate (Na3H5O7·H2O) 2.94g, adds distilled water 100ml and is made into B solution；
3. A, B liquid is pressed 1:1 mixing by the used time, measures pH value with PH meter, regulates PH=4.3, be i.e. required configuration STZLemon Lemon acidBuffer solution.
2nd, method
2.1st, the foundation of diabetic nephropathy model
Normal SD rats is fed 1 week after adapting to environment, fasting 12 hours, choose 100, in addition to blank group 10, its
Yu 90 with 65mg kg-1Dosage once abdominal cavity injection STZ, STZ are dissolved in 0.1mol l-1Citric acid-sodium citrate buffer solution
(pH4.3) being made into the solution of 1% in, volume injected is carried out according to 0.5ml/100g.Cut tail after 72 hours and take blood survey blood sugar, with blood
Sugar concentration >=16.7mmol l-1As diabetes model Criterion, become mould 77 altogether, by the eliminating experiment of non-Cheng Mo.
2.2nd, packet and medication
One-tenth mould rat is randomly divided into 7 groups: model group, diabetes pill group, giant knotweed rhizome general anthraquinone group, arasaponin group, this
Bright composition group (wherein, giant knotweed rhizome general anthraquinone and arasaponin mass ratio are respectively 1:1,1.5:1,1:1.5), often organizes 11.
Giant knotweed rhizome general anthraquinone group gavages 8.75mg/Kg (being equivalent to crude drug 15g), and arasaponin group gavages 35mg/Kg and (is equivalent to adult
Take arasaponin preparation XUESAITONG PIAN 7 times), (wherein, 1:1 group is 43.75mg to composition group；1.5:1 group is
48.13mg；1.5:1 group is 52.5mg), it is that 600mg/Kg (is equivalent to dosage of being grown up that diabetes pill group gavages diabetes pill dosage
7 times), blank group and model group rats every 100g body weight gavage the physiological saline of 1ml, are administered once daily, successive administration 8 weeks.
2.3rd, collection of specimens and process
Detect the blood glucose value often organizing rat upon administration week about.Cut tail with the three stable blood glucose monitoring systems of promise to take blood and survey sky
Abdomen blood sugar.Metabolic cage accurately collects 24h urine volume, and fresh urine sample, with 3000rpm centrifugation 15min, is gone in-20 DEG C of refrigerators of sediment
Preserve, in order to the detection of 24h Urine proteins and microdose urine protein；Abdominal aortic blood about 5ml, taken blood is with 3000rpm
Centrifugation 10min, placing a few minutes takes serum-80 DEG C and saves backup.Other abdominal aortic blood 5ml, liquaemin anti-freezing, supply
Measure the indexs such as fasting blood-glucose, four items of blood lipid tests, Hemorheology；Taking double kidney, removing kidney peplos, and survey its quality, double kidneys are with 4%
Formalin is fixed, and carries out HE dyeing and does pathological section.
2.4th, Testing index and assay method
2.4.1, general index determining: measure weekly rat fasting blood-glucose, a body weight, and the drink of observed and recorded animal
The ordinary circumstance such as water, dietary amount, urine volume, the state of mind etc., stool；
2.4.2, body weight and renal index measure: timing precise respectively organizes the body weight of SD rat weekly, calculates each group
The change of body weight.At 8th weekend, take out left and right kidney after taking blood, wash except kidney peplos, and after blotting with blotting paper, use electricity
Sub-balance correct amount, according to formula renal index (KW/BW)=[bilateral renal weight (KW) sum (g)/body weight (BW) (g)]
× 100 calculate；
2.4.3, microdose urine protein measures: before administration after mould, and be administered for the 4th, 8 weekends, take SD rat and be placed in
In metabolic cage, after 1, every cage adapts to 1 day, water is can't help in fasting, collects 24h urine with conical flask, and records urine volume.By taken urine
Liquid, with 3000rpm, after centrifugal 10min, after taking supernatant dilution several times, uses coomassie brilliant blue quantitatively to detect, sternly
Lattice by specification operates.
2.4.4, blood index detection and Biochemical Indexes: use LGR80A blood rheological instrument detection whole blood to stick
Degree, plasma viscosity.The index determining such as FBG, PBG, TC, HDL-C, LDL-C, TG, Cr.Use ELIASA detection, strictly illustratively
Book operates.
2.4.5, renal tissue microsection manufacture step: after nephridial tissue is fixed by paraformaldehyde solution, repairs tissue block, flowing water
Rinse, gradient alcohol dehydration, each transparent 30min of dimethylbenzene I, II, waxdip, finally embed, will after tissue nature cooling
It is stopped in echelon.Wax stone is fixed on slicer, mixes up distance, be cut into 5um slab.Then by careful for the slice, thin piece that cuts
Put into stand piece machine exhibition piece, pick up with slide after slice, thin piece launches, carry out mark, baking piece is stand-by.
(1) section HE staining procedure
1. the alcohol of dimethylbenzene, variable concentrations is used to dewax to water the section being baked.
2. brazilwood extract dyeing 10 minutes.
3. flowing water rinses 2～3 minutes for the first time, and hydrochloride alcohol breaks up 30 seconds；Second time washing 15～20 minutes, then with steaming
Distilled water is soaked 5 minutes, the eosin stains of 0.5% 25～30 minutes；Third time washing, gradient alcohol dehydration.
4. each transparent 10 minutes of dimethylbenzene I, II.
5. drip appropriate neutral gum mounting, slow covered, avoid bubble to produce as far as possible, gently sassafras go unnecessary
Natural gum, dry, to be seen.
(2) SABC step
First, carry out, according to antibody specification, the concentration that preliminary experiment determines the antibody diluent of different antibodies, select optimal
Developing concentration, the optium concentration of this reagent is 1:200.SABC step is as follows:
1. cut into slices and dewax 3 times through dimethylbenzene, 10 minutes every time；Graded ethanol (the 50%th, the 70%th, the 95%th, 100%) is respectively dehydrated
Once, every time 5 minutes；PBS washes 3 times, 5 minutes every time.
2. hatched 10 minutes by 3% hydrogen peroxide of water recently distilled preparation, block endogenous peroxidase activity；
PBS washes 3 times, 5 minutes every time.
3. section is put in the sodium citrate buffer solution of 0.01mol/L, use microwave boiling method to carry out antigen retrieval, cold
But to room temperature, use distilled water flushing 3 times, then balance 5 minutes with PBS.
4. drip BSA confining liquid, place 20 minutes in section is placed in wet box；Incline unnecessary serum, drips each index
One resists, and negative control PBS replaces one to resist, and room temperature is placed 20 minutes, and 4 DEG C of refrigerator cold-storages are overnight.
5. section is taken out from refrigerator to place and recover room temperature, PBS 3 times, 3 minutes every time；Dry section with filter paper
Around leaving over liquid, dropping two resists, and hatches 30 minutes in 37 DEG C of incubators, PBS flushing 3 times, 5 minutes every time.
6. wiping dry section and around leaving over liquid, drip horseradish enzyme labeling, hatch 30 minutes in 37 DEG C of incubators, PBS rinses 3
Secondary, 5 minutes every time.
7. DAB colour developing, basis of microscopic observation Color after dropping, running water rinses repeatedly.
8. being redyed 2 minutes by haematoxylin dye liquor, running water fully rinses；Hydrochloride alcohol, running water fully rinses.
9. gradient alcohol dehydration, dimethylbenzene is transparent, neutral gum mounting.
10. use light microscope shooting photo, SABC image IPP7.0 analyzes picture, compare section integration
Optical density.
(2), statistical procedures
Use SPSS12.0for windows statistical software to carry out data analysis, use mean ± standard deviation
Representing result, comparing employing one-way analysis of variance (One-Way ANOVE) between measurement data group, ranked data use Ridit
Analyze.
(3), result:
1st, the impact on rat body weight
There is the increase of conspicuousness from naive animals body weight shown in Fig. 1, but the body weight of model group SD rat is gradually reduced, from
Shown in Fig. 2 with model group rats body weight compared with, the 6th week diabetes pill group, giant knotweed rhizome general anthraquinone group, giant knotweed rhizome general anthraquinone and the total soap of pseudo-ginseng
Glycosides proportioning (1.5:1/1:1.5) group can dramatically increase the body weight of SD rat, diabetes pill group and giant knotweed rhizome general anthraquinone group, the total soap of pseudo-ginseng
Glycosides group and giant knotweed rhizome general anthraquinone are respectively organized with arasaponin proportioning all can significantly increase SD rat body weight.Result is as shown in table 1:
The impact on rat body weight for the table 1
2nd, the impact on rat urine albumen and microdose urine protein
2.1st, rat urine albumen is affected
From shown in Fig. 3, table 2: the Rat 24 h microdose urine protein content of model group rats compared with normal group significantly raises.
Compared with model group, each administration group can substantially reduce diabetic nephropathy rats twenty-four-hour urine microalbumin content, has statistics
Learn meaning (p 0.05)；1:1.5 group declines relatively giant knotweed group, pseudo-ginseng group and becomes apparent from, and has statistical significance (p 0.05)；
The impact on rat urine albumen and microdose urine protein for the table 2
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
Rat urine albumen is affected by 2.2
From shown in Fig. 4, table 3: the Rat 24 h urine protein content of model group rats compared with normal group significantly raises.With model
Group is compared, and each administration group can substantially reduce diabetic nephropathy rats twenty-four-hour urine protein content, has statistical significance (p
0.05)；1:1.5 group and 1.5:1 group decline relatively giant knotweed group, pseudo-ginseng group and become apparent from, and have statistical significance (p 0.05).
The impact on rat urine albumen and urinary albumin for the table 3
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
3rd, the impact on Renal Function in Rats
From shown in Fig. 5, table 4: rat urea nitrogen, the serum creatinine content of model group rats compared with normal group significantly raise.With mould
Type group is compared, and each administration group can substantially reduce diabetic nephropathy rats urea nitrogen, serum creatinine content, has statistical significance (p
0.05)；Compatibility group serum creatinine content declines relatively giant knotweed group, pseudo-ginseng group and becomes apparent from, and has statistical significance (p 0.05)；Compatibility
Group urea nitrogen content declines relatively pseudo-ginseng group and becomes apparent from, and has statistical significance (p 0.05).
The impact on Renal Function in Rats for the table 4
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
4th, the impact on rat kidney index
From shown in Fig. 6, table 5: the renal index of model group rats compared with normal group significantly raises.Compared with model group, respectively give
Medicine group can be substantially reduced the dirty index of diabetic nephropathy, has statistical significance (p 0.05)；Compatibility group urea nitrogen content
Decline and become apparent from compared with pseudo-ginseng group, there is statistical significance (p 0.05).
The impact on rat kidney for the table 5
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
5th, lipid metaboli is affected
From shown in Fig. 7, table 6: TC, TG, HDL-C, LDL-C content of model group rats compared with normal group significantly raises, and has system
Meaning (p 0.05) learned by meter.Compared with model group, each administration group can be substantially reduced diabetic nephropathy rats TC, TG, HDL-C,
LDL-C content, has statistical significance (p 0.05)；Compatibility group TC, TG, HDL-C, LDL-C content are compared with alone group of giant knotweed, pseudo-ginseng
There is reduction trend in various degree.
The impact on rat TC, TG, HDL-C, LDL-C for the table 6
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
6th, on hemorheological impact
Analyze from shown in Fig. 8, table 7: the whole blood height of model group rats compared with normal group is cut, the notable (p of undercut viscosity reduction effect
＜ 0.05).Compared with model group, each administration group can be substantially reduced diabetic nephropathy rats whole blood height cut, undercut viscosity, there is system
Meaning (p 0.05) learned by meter；Compatibility group whole blood height is cut, undercut viscosity all has reduction trend compared with giant knotweed, alone group of pseudo-ginseng.
In terms of platelet adhesion reaction rate, the plasma viscosity of model group rats compared with normal group, platelet adhesion reaction rate reducing effect
Significantly (p ＜ 0.05).Compared with model group, each administration group can be substantially reduced diabetic nephropathy rats plasma viscosity, blood platelet sticks
Attached rate, has statistical significance (p 0.05)；In addition to 1:1 group remaining each compatibility group plasma viscosity, platelet adhesion reaction rate compared with giant knotweed,
Alone group of low effect of pseudo-ginseng is notable (p ＜ 0.05).
Table 7 rheol impact on rat serum
7th, ImmunohistochemistryResults Results
The expression of TGF-β 1 in 7.1 nephridial tissues
From shown in Fig. 9, table 8: the content of the renal tissues of rats TGF-β 1 of model group rats compared with normal group expresses notable rising.
Compared with model group, each administration group can substantially reduce the content of diabetic nephropathy tissue T GF-β 1, has statistics meaning
Justice (p 0.05)；1:1 group and 1.5:1 group content reduce notable compared with giant knotweed group, pseudo-ginseng group, have statistical significance (p 0.05).
The content of table 8 renal tissues of rats TGF-β 1 is expressed
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
The expression of AGEs in 7.2 nephridial tissues
From shown in Figure 10, table 9: the content of the renal tissues of rats AGEs of model group rats compared with normal group expresses notable rising.
Compared with model group, each administration group can substantially reduce the content of diabetic nephropathy tissue AGEs, has statistical significance
(p 0.05)；1:1 group and 1.5:1 group content reduce more notable compared with giant knotweed group, pseudo-ginseng group, have statistical significance (p
0.05)。
The expression of AGEs in table 9 renal tissues of rats
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
The expression of RAGE in 7.3 nephridial tissues
There is table the 10th, Figure 11 it can be seen that the content of renal tissues of rats RAGE of model group rats compared with normal group is expressed notable
Raise.Compared with model group, each administration group can substantially reduce the content of diabetic nephropathy tissue RAGE, has statistics
Meaning (p 0.05)；Compatibility group content reduces more notable compared with giant knotweed, alone group of pseudo-ginseng, and has statistical significance (p
0.05)。
The expression of RAGE in table 10 renal tissues of rats
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
The expression of FN in 7.4 nephridial tissues
By table the 11st, Figure 12 it can be seen that the content of the renal tissues of rats FN of model group rats compared with normal group expresses notable liter
High.Compared with model group, each administration group can substantially reduce the content of diabetic nephropathy tissue FN, has statistical significance
(p 0.05)；Compatibility group 1:1 and 1:1.5 content more reduce compared with giant knotweed, alone group of pseudo-ginseng, have statistical significance (p
0.05)。
The expression of FN in table 11 renal tissues of rats
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
The expression of Smad3 in 7.5 nephridial tissues
By table the 12nd, Figure 13 it can be seen that compared with model group, each administration group Smad3 expression all decreases, associating
Group effect is better than pseudo-ginseng group, combines group 1.5:1 group and is better than other and combines group, and diabetes pill group effect is best, and has conspicuousness, P
0.01。
The expression of Smad3 in table 12 renal tissues of rats
Note: # represents and compares P 0.05 with normal group, and * represents and compares P 0.05 with model group
△ represents and compares P 0.05 with giant knotweed group, ▲ represent and compare P 0.05 with pseudo-ginseng group
8th, renal pathology sexually revises
HE dyes display: normal rats glomerulus, renal tubule structural integrity, skin, medullary substance boundary are obvious, glomerulus base
Counterdie is complete, and extracellular matrix is normal.Model group skin, medullary substance boundary are unintelligible, it is seen that obvious glomerulus hyperplasia, basement membrane thickened,
Capsular space is narrow, it is seen that obvious inflammatory cell infiltration.The improvement in various degree of administration group situation, but still show in various degree
Injury of kidney.(see annex figure)
(4), conclusion
The present invention is according to the basic theory of tcm of etiological treatment, by using invigorating blood circulation in Integral animal experiment, this experiment
Diabetic nephropathy is intervened by stasis of blood medicine giant knotweed rhizome general anthraquinone and arasaponin compatibility, may certify that it is right as rain, and
Effect is notable.
The present invention in terms of renal function, Urine proteins, hemorheology etc. to giant knotweed rhizome general anthraquinone and arasaponin in diabetes
The mechanisms of therapeutic action of ephrosis is tested, and in experiment, model group rats occurs in that microdose urine protein, creatinine, urea nitrogen
Too high levels, it can be determined that rat model occurs in that early diabetic nephropathy pathology, and applies giant knotweed rhizome general anthraquinone and the total soap of pseudo-ginseng
After glycosides proportioning component, this pathological phenomenon is improved, and verifies that this Experimental agents has protective effect to diabetic nephropathy kidney,
And renal function can be improved.Improving renal function and blood circulation, fall when result data be can be seen that Papillary compatibility component
Low urine protein content, reduction blood fat thickness aspect play the role of to become apparent from effect than alone giant knotweed rhizome general anthraquinone, arasaponin
Really, the two use in conjunction effect is more notable:
1st, diabetic nephropathy renal function is improved significantly by giant knotweed rhizome general anthraquinone and arasaponin compatibility component
Giant knotweed rhizome general anthraquinone improves significantly with the renal function to diabetic nephropathy rats for the arasaponin compatibility component
Effect, can reduce the excretion of microdose urine protein, urea nitrogen, creatinine, thus mitigate the symptom of diabetic nephropathy.
2nd, giant knotweed rhizome general anthraquinone and arasaponin and compatibility component Hemorheology tool thereof have some improvement
Giant knotweed rhizome general anthraquinone significantly changes with the hemorheology learning aid to diabetic nephropathy rats for the arasaponin compatibility component
Kind effect, can reduce and significantly reduce WBV, blood sugar viscosity and suppression platelet aggregation, suppress diabetic nephropathy rats
The generation of thrombus.Blood samples of patients dyshaemia, perfused tissue deficiency, ischemic, anoxic and metabolism can be improved in some aspects
The symptoms such as obstacle.
3. giant knotweed rhizome general anthraquinone and the impact on diabetic nephropathy Urine proteins for the arasaponin compatibility component
Giant knotweed rhizome general anthraquinone significantly improves with the Urine proteins tool to diabetic nephropathy rats for the arasaponin compatibility component and makees
With substantially reducing diabetic nephropathy rats 24h Urine proteins, microdose urine protein content.
4. giant knotweed rhizome general anthraquinone and arasaponin compatibility component are better than alone giant knotweed rhizome general anthraquinone, arasaponin, its compatibility
Component is particularly suited for the prevention and treatment of diabetic nephropathy.
The invention provides giant knotweed rhizome general anthraquinone to treat in the medicine of diabetic nephropathy in preparation with notoginseng total saponin compounds
Application.Wherein said giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds include that weight ratio is (1:1), (1:1.5), (1.5:1)
Giant knotweed rhizome general anthraquinone and arasaponin ratio.
The giant knotweed rhizome general anthraquinone of the present invention and the weight of arasaponin are than most preferably 1:1.5.
Application of the present invention, wherein said composition is by reducing blood fat, reducing blood viscosity, improve kidney work(
Diabetic nephropathy can be treated.
Application of the present invention, wherein said composition be by reduce Urine proteins eject treatment diabetic nephropathy
's.
Application of the present invention, wherein said composition is to be controlled by lowering the expression of transforming growth factor β_1
Treat diabetic nephropathy.
Application of the present invention, wherein said composition is to treat diabetes by lowering the expression of Smad3 albumen
Ephrosis.
Application of the present invention, wherein said composition is to treat diabetes by lowering the expression of laminin
Ephrosis.
Application of the present invention, wherein said composition is by lowering advanced glycation end products, advanced glycosylation endproduct end product
Diabetic nephropathy is treated in the expression of thing acceptor.
Present invention demonstrates that giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds can mitigate diabetes kidney damage, and its effect is excellent
In alone giant knotweed rhizome general anthraquinone and arasaponin, prompting giant knotweed rhizome general anthraquinone can produce synergistic effect with compatibility arasaponin,
Delay the generation of diabetic nephropathy.Therefore, the two compatibility uses and can dramatically increase curative effect, mitigates toxicity, reduces dose.
There is provided more preferable medicament selection for Early renal failure patient clinically, be treatment early diabetic nephropathy medicine
On innovation, economic and social benefit is notable.
Claims (5)
1. a giant knotweed rhizome general anthraquinone and notoginseng total saponin compounds, it is characterised in that described giant knotweed rhizome general anthraquinone and the total soap of pseudo-ginseng
The mass ratio of glycosides is: giant knotweed rhizome general anthraquinone: arasaponin=1-1.5:1-1.5.
2. giant knotweed rhizome general anthraquinone according to claim 1 and notoginseng total saponin compounds, it is characterised in that described giant knotweed is total
Anthraquinone with the mass ratio of arasaponin is: giant knotweed rhizome general anthraquinone: arasaponin=1:1.
3. giant knotweed rhizome general anthraquinone according to claim 1 and notoginseng total saponin compounds, it is characterised in that described giant knotweed is total
Anthraquinone with the mass ratio of arasaponin is: giant knotweed rhizome general anthraquinone: arasaponin=1.5:1.
4. giant knotweed rhizome general anthraquinone according to claim 1 and notoginseng total saponin compounds, it is characterised in that described giant knotweed is total
Anthraquinone with the mass ratio of arasaponin is: giant knotweed rhizome general anthraquinone: arasaponin=1:1.5.
5. the giant knotweed rhizome general anthraquinone described in any one of right 1 or 2-4 and notoginseng total saponin compounds are at preparation treatment early diabetes
Application in ephrosis medicine.
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101530515A (en) * | 2008-03-13 | 2009-09-16 | 北京绿源求证科技发展有限责任公司 | Traditional Chinese medicine for treating diabetes mellitus complicated by intumescent prostate |
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2016
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101530515A (en) * | 2008-03-13 | 2009-09-16 | 北京绿源求证科技发展有限责任公司 | Traditional Chinese medicine for treating diabetes mellitus complicated by intumescent prostate |
Non-Patent Citations (2)
| Title |
|---|
| 林育等: "中医药干预糖尿病肾病TGF-β/Smad通路的研究现状", 《中国中医药现代远程教育》 * |
| 陈曦等: "中药有效成分防治糖尿病肾病的实验研究进展", 《安徽医药》 * |
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