CN101897716B - Application of astilbin in preparing drugs capable of curing or preventing acute renal failure - Google Patents
Application of astilbin in preparing drugs capable of curing or preventing acute renal failure Download PDFInfo
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- CN101897716B CN101897716B CN2010102551763A CN201010255176A CN101897716B CN 101897716 B CN101897716 B CN 101897716B CN 2010102551763 A CN2010102551763 A CN 2010102551763A CN 201010255176 A CN201010255176 A CN 201010255176A CN 101897716 B CN101897716 B CN 101897716B
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- astilbin
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- renal failure
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- ZROGCCBNZBKLEL-FHXNIQKESA-N Astilbin Natural products O([C@H]1[C@@H](c2cc(O)c(O)cc2)Oc2c(c(O)cc(O)c2)C1=O)[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](C)O1 ZROGCCBNZBKLEL-FHXNIQKESA-N 0.000 title claims abstract description 142
- ZROGCCBNZBKLEL-MPRHSVQHSA-N astilbin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1C(=O)C2=C(O)C=C(O)C=C2O[C@@H]1C1=CC=C(O)C(O)=C1 ZROGCCBNZBKLEL-MPRHSVQHSA-N 0.000 title claims abstract description 142
- 239000003814 drug Substances 0.000 title claims abstract description 18
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- 229940079593 drug Drugs 0.000 title abstract description 7
- 238000002360 preparation method Methods 0.000 claims description 30
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- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
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- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
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- 150000002333 glycines Chemical class 0.000 description 1
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
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- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an application of astilbin in preparing drugs capable of curing or preventing acute renal failure and kidney fibrosis.
Description
The application divides an application for Chinese application number 200610069223.9.Original bill application name is called: the application of astilbin in the medicine of preparation treatment or prevention acute or chronic renal failure and renal fibrosis, the applying date is: on JIUYUE 27th, 2006.
Technical field
The present invention relates to the application of astilbin in the medicine of preparation treatment or prophylaxis of acute renal failure.
Background technology
Astilbin have pharmacological actions such as resisting myocardial ischemia, immunomodulating, antiinflammatory, analgesia [Shao Chunhong, Xinhua, Zhou Chengming, etc. red Rhizoma Smilacis Glabrae glycosides is to the protective effect of rat heart muscle ischemia. Xinjiang Medicine University's journal, 2000,23 (3): 205-207.; Gao Sihai, Pan Tiecheng. the extraction of Astilbin reaches the protective effect research to myocardial ischemia reperfusion injury. Chinese practical Chinese and western medicine magazine, 2003,3:1693-1694].The inventor has invented the application of astilbin in the medicine of preparation treatment or prevention acute or chronic renal failure and renal fibrosis through a large amount of experimentatioies.
Summary of the invention:
The invention provides the application of astilbin in the medicine of preparation treatment or prevention acute or chronic renal failure.
The invention provides the application of astilbin in the medicine of preparation treatment or prevention renal fibrosis.
The invention provides with the astilbin is the pharmaceutical composition that is used for renal failure and renal fibrosis of active component.
Astilbin provided by the invention is when being used for acute or chronic renal failure and renal fibrosis, and the using dosage scope is 25mg～1000mg during its injection; Preferred 25～500mg, the using dosage scope is 50mg～2000mg when oral; Preferred 50～1000mg.
Astilbin provided by the invention can be by document disclosed method preparation, preferably preparation as follows: add concentration after the Poria pulverizing medicinal materials that fetches earth and be 80% alcohol solution dipping and spend the night; Extract 2 times, each 10 times of amount volumes merge concentrated dealcoholysis to 5 times amount volume with extracting solution, are diluted with water to 20 times of amount volumes again, place deposition; Cross polyamide chromatography post on the leaching supernatant, earlier with 6 column volumes of sour water (pH=2) eluting, 8 column volumes of the alcoholic solution eluting of reuse 20% concentration, the collection eluent has been concentrated into deposition and has separated out; Cross the leaching deposition, drying obtains the astilbin bullion, and recrystallize promptly gets.
Astilbin pharmaceutical composition provided by the invention can add corresponding adjuvant according to the preparation needs, exists with forms such as injection, tablet, pill, granule, capsule, syrup, is preferably freeze-dried powder and capsule.Various dosage form provided by the invention all can adopt the pharmacy conventional method to be prepared from.
The inventor has carried out following test and has confirmed to treat or prevent the application in the medicine of acute and chronic nephritis and acute or chronic renal failure, but pharmacological action is not limited only to this.
The practical implementation instance:
Preparation example 1: the preparation of astilbin
The Poria medical material 5kg that fetches earth adds concentration and is 80% alcohol solution dipping and spends the night after the pulverizing; Extract 2 times, 60L for the first time, 40L for the second time merges extracting solution and concentrates dealcoholysis to 5L, is diluted with water to 20L again, places deposition; Cross polyamide chromatography post (CV=5L) on the leaching supernatant, earlier with 6 column volumes of sour water (pH=2) eluting, 8 column volumes of the alcoholic solution eluting of reuse 20% concentration, the collection eluent has been concentrated into deposition and has separated out; Cross the leaching deposition, drying obtains astilbin bullion 42g, and recrystallize obtains the pure article 34g of astilbin, purity 95.8%.
Preparation example 2: the preparation of astilbin
The Poria medical material 5kg that fetches earth, pulverizing the back, to use 20 times of concentration be 95% alcoholic solution percolation; Merge percolate, concentrate dealcoholysis, be diluted with water to 15L again, place deposition to 3L; Cross polyamide chromatography post (CV=5L) on the leaching supernatant, earlier with 6 column volumes of sour water (pH=2) eluting, 6 column volumes of the alcoholic solution eluting of reuse 30% concentration, the collection eluent has been concentrated into deposition and has separated out; Cross the leaching deposition, drying obtains astilbin bullion 38g, and recrystallize obtains the pure article 28g of astilbin.Purity 97.8%.
The preparation for preparing routine 3 astilbin tablets
Cross 100 mesh sieves after taking by weighing 40.0g astilbin, 85.0g Icing Sugar, 40.0g lactose and the abundant mix homogeneously of 23.0g carboxymethyl starch sodium, add an amount of 3%PVP
K30Aqueous solution is made soft material in right amount, and 20 mesh sieves are granulated, 60 ℃ of dryings 3 hours, and 18 mesh sieve granulate add the 2.0g magnesium stearate, press 1000 behind the mix homogeneously, and every agreement that contracts a film or TV play to an actor or actress 200mg promptly gets.
Prepare routine 4 astilbin preparation of soft capsule
Take by weighing and make 1000 soft capsules after the 20.0g astilbin adds the abundant mix homogeneously of the medicinal Oleum Glycines of 200ml, every about 200mg promptly gets.
The preparation for preparing routine 5 Herba astilbes chinensis aglycon drop pill
Get 30mg Macrogol 4000 and 20.0g astilbin respectively, mix heating and melting in rearmounted 75 ℃ of waters bath with thermostatic control, put 75 ℃ of insulations under stirring and made in 1 hour and be uniformly dispersed; Medicinal liquid is transferred in 75 ℃ of constant temperature storage tanks of drop pill machine, is 5.0/6.0mm at the water dropper bore, drips 60 droplets/minute of speed; Coolant is a dimethicone, and under 10 ℃ of conditions of coolant temperature, regulating the drop pill ball heavily is 60mg; Drip and process 1000 balls, remove the lip-deep liquid coolant packing of drop pill, promptly get.
Prepare routine 6 astilbin injection preparation
Astilbin 30.0g
Tween 80 1g
Add the injection water to 1000ml
Process 1000 altogether
Test of the influence of 1 astilbin to the rat acute renal failure
1.1 medicine and reagent
Astilbin is by preparation example 1 and 6 preparations of preparation example
(Belgian Pharmacia S.P.A., specification: 40mg/ props up prednisolone, lot number: 040706)
Creatinine and blood urea nitrogen test kit (are given birth to scientific & technical corporation, lot number: 050606) in Beijing
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, natural drug Engineering Technical Research Centre zoopery center, Shandong Province provides.The quality certification number: No. 200106005, Shandong kinoplaszm word.
1.2 test method and result
130 of rats, body weight 150-200g, 1 week of animal feeding; Animal is divided into 13 groups, i.e. normal group, model group; Prednisolone (12mg/kg) group, astilbin intravenous injection low dose of (1mg/kg) group, dosage in the astilbin intravenous injection (2.5mg/kg) group; Astilbin intravenous injection heavy dose of (10mg/kg) group 1, astilbin intravenous injection heavy dose of (25mg/kg) group 2, astilbin intravenous injection heavy dose of (50mg/kg) group 3; Astilbin intravenous injection heavy dose of (100mg/kg) group 4, astilbin is irritated stomach dosage (5mg/kg) group 1, and astilbin is irritated stomach dosage (50mg/kg) group 2; Astilbin is irritated stomach dosage (100mg/kg) group 3, and astilbin is irritated stomach dosage (200mg/kg) group 4.Glycerol is made into 50% (V/V), except that normal group, prohibits water to rat, disposable intramuscular injection behind the 16h, and dosage is 1mL/100g, each organized successive administration 3 days, got blood from eye socket, measured serum creatinine and blood urea nitrogen (creatinine and blood urea nitrogen kit measurement creatinine and blood urea nitrogen)
Can find out from table 1 result, dosage in the astilbin intravenous injection (2.5mg/kg) group, astilbin is irritated stomach dosage (5mg/kg) group 1 and is reduced rat acute renal failure serum creatinine and blood urea nitrogen (comparing p＜0.05 with model group); Prednisolone (12mg/kg) group; Astilbin intravenous injection heavy dose of (10mg/kg) group 1; Astilbin intravenous injection heavy dose of (25mg/kg) group 2, astilbin intravenous injection heavy dose of (50mg/kg) group 3, astilbin intravenous injection heavy dose of (100mg/kg) group 4; Astilbin is irritated stomach dosage (50mg/kg) group 2; Astilbin is irritated stomach dosage (100mg/kg) and is organized 3, and astilbin is irritated stomach dosage (200mg/kg) group 4 and obviously reduced rat acute renal failure serum creatinine and blood urea nitrogen (comparing p＜0.01 with model group); Astilbin intravenous injection heavy dose of (50mg/kg) group 3 reduces rat acute renal failure serum creatinine and blood urea nitrogen and astilbin intravenous injection heavy dose of (100mg/kg) group 4 relatively, there was no significant difference; Stomach dosage (100mg/kg) group 3 of irritating astilbin reduces rat acute renal failure serum creatinine and blood urea nitrogen and astilbin and irritates stomach dosage (200mg/kg) group 4 relatively, there was no significant difference.
Table 1 astilbin is to the influence of rat acute renal failure serum creatinine and blood urea nitrogen
Group dosage (mg/kg) serum creatinine (mg/dL) serum urea nitrogen (mg/dL)
Normal group---0.45 ± 0.05 9.65 ± 2.65
Model group--2.06 ± 0.22 40.45 ± 4.50
Prednisolone group 12 1.11 ± 0.13
*16.21 ± 3.25
*
1 1.90±0.29 38.05±3.43
2.5 1.81±0.17
* 35.84±3.62
*
10 1.52±0.37
** 30.32±7.36
**
Astilbin intravenous injection group 25 1.32 ± 0.28
*26.52 ± 4.19
*
50 1.20±0.22
** 21.85±3.45
**
100 1.19±0.39
** 21.55±5.88
**
5 1.82±0.18
* 36.27±3.82
**
Astilbin is irritated stomach group 50 1.67 ± 0.28
*31.25 ± 5.60
*
100 1.53±0.28
** 28.56±3.95
**
200 1.53±0.26
** 27.96±5.80
**
*, p＜0.05,
*, compare with model group p＜0.01
Test 2 astilbins cause the rat chronic renal failure to adenine influence
2.1 medicine and reagent
Astilbin is by preparation example 1 and 6 preparations of preparation example
Adenine (Changzhou China Tonghua worker company)
(Belgian Pharmacia S.P.A., specification: 40mg/ props up prednisolone, lot number: 040706)
Creatinine and blood urea nitrogen test kit (are given birth to scientific & technical corporation, lot number: 050606) in Beijing
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, natural drug Engineering Technical Research Centre zoopery center, Shandong Province provides.The quality certification number: No. 200106005, Shandong kinoplaszm word.
130 of rats, body weight 150-200g in 1 week of animal feeding, is divided into 13 groups with animal; Be normal group, model group, prednisolone (12mg/kg) group, astilbin intravenous injection low dose of (1mg/kg) group; Dosage in the astilbin intravenous injection (2.5mg/kg) group, astilbin intravenous injection heavy dose of (10mg/kg) group 1, astilbin intravenous injection heavy dose of (25mg/kg) group 2, astilbin intravenous injection heavy dose of (50mg/kg) group 3; Astilbin intravenous injection heavy dose of (100mg/kg) group 4, astilbin is irritated stomach dosage (5mg/kg) group 1, and astilbin is irritated stomach dosage (50mg/kg) group 2, and astilbin is irritated stomach dosage (100mg/kg) group 3; Astilbin is irritated stomach dosage (200mg/kg) group 4, and except that normal group, every rat ip adenine 200mg/kg is after 7 days; Big rathole frame is got blood, measures serum creatinine and blood urea nitrogen, observes the modeling situation; Since administration in the 8th day, successive administration 14 days was got blood from eye socket; Measure serum creatinine and blood urea nitrogen (creatinine and blood urea nitrogen kit measurement creatinine and blood urea nitrogen), put to death and do the pathology section, observe the pathological change of renal function.
Can find out from table 2 result, dosage in the astilbin intravenous injection (2.5mg/kg) group, astilbin is irritated stomach dosage (5mg/kg) group 1 and is reduced rat chronic renal failure serum creatinine and blood urea nitrogen (comparing p＜0.05 with model group); Prednisolone (12mg/kg) group; Astilbin intravenous injection heavy dose of (10mg/kg) group 1; Astilbin intravenous injection heavy dose of (25mg/kg) group 2, astilbin intravenous injection heavy dose of (50mg/kg) group 3, astilbin intravenous injection heavy dose of (100mg/kg) group 4; Astilbin is irritated stomach dosage (50mg/kg) group 2; Astilbin is irritated stomach dosage (100mg/kg) and is organized 3, and astilbin is irritated stomach dosage (200mg/kg) group 4 and obviously reduced rat chronic renal failure serum creatinine and blood urea nitrogen (comparing p＜0.01 with model group); Astilbin intravenous injection heavy dose of (50mg/kg) group 3 reduces rat chronic renal failure serum creatinine and blood urea nitrogen and astilbin intravenous injection heavy dose of (100mg/kg) group 4 relatively, there was no significant difference; Stomach dosage (100mg/kg) group 3 of irritating astilbin reduces rat chronic renal failure serum creatinine and blood urea nitrogen and astilbin and irritates stomach dosage (200mg/kg) group 4 relatively, there was no significant difference.
Pathologic finding: normal control group nephridial tissue structure is normal, and model group has obvious nephridial tissue crystalline deposit thing, and renal tubules destroys; Atrophy, tube chamber diminishes, wherein visible lymphocytic infiltration and local proliferation of fibrous tissue; The glomerule enlargement, the degeneration of glomerular epithelium cell formation of vacuoles, a large amount of unconsolidated materials appear down in endotheliocyte; Basement membrane thickened, quantitative analysis renal tubules area and glomerular volume, model group and normal control group relatively have significant difference.Astilbin is respectively organized each dose groups and is obviously alleviated with dosage increase degree of injury, but returns to normal level not yet.
Table 2 astilbin is to the influence of rat chronic renal failure serum creatinine and blood urea nitrogen
Group dosage (mg/kg) serum creatinine (mg/dL) serum urea nitrogen (mg/dL)
Normal group---0.49 ± 0.07 9.85 ± 2.55
Model group--2.04 ± 0.22 40.53 ± 4.51
Prednisolone group 12 1.15 ± 0.13
*18.21 ± 3.25
*
1 1.90±0.22 38.01±3.24
2.5 1.80±0.18
* 35.91±3.60
*
10 1.52±0.37
** 30.42±7.36
**
Astilbin intravenous injection group 25 1.32 ± 0.28
*26.76 ± 4.19
*
50 1.20±0.22
** 22.07±3.45
**
100 1.19±0.39
** 21.85±5.88
**
5 1.82±0.19
* 36.37±3.85
**
Astilbin is irritated stomach group 50 1.67 ± 0.28
*31.47 ± 5.60
*
100 1.55±0.28
** 28.46±3.95
**
200 1.54±0.26
** 27.86±5.30
**
*, p＜0.05,
*, compare with model group p＜0.01
Test 3 astilbins cause the rat chronic renal failure to the nephrectomy influence
3.1 medicine and reagent
Astilbin is by preparation example 1 and 6 preparations of preparation example
(Belgian Pharmacia S.P.A., specification: 40mg/ props up prednisolone, lot number: 040706)
Creatinine and blood urea nitrogen test kit (are given birth to scientific & technical corporation, lot number: 050606) in Beijing
Laboratory animal: regular grade Wistar rat, male, body weight 280g-350g, natural drug Engineering Technical Research Centre zoopery center, Shandong Province provides.The quality certification number: No. 200106005, Shandong kinoplaszm word.
3.2 test method and result
195 of rats, body weight 150-200g in 1 week of animal feeding, is divided into 13 groups with animal; Every group 15, i.e. normal group, model group, prednisolone (12mg/kg) group; Astilbin injection low dose of (1mg/kg) group, dosage (2.5mg/kg) group in the astilbin injection, astilbin injection heavy dose of (10mg/kg) group 1, astilbin injection heavy dose of (25mg/kg) group 2; Astilbin injection heavy dose of (50mg/kg) group 3, astilbin injection heavy dose of (100mg/kg) group 4, astilbin is irritated stomach dosage (5mg/kg) group 1, and astilbin is irritated stomach dosage (50mg/kg) group 2; Astilbin is irritated stomach dosage (100mg/kg) group 3, and astilbin is irritated stomach dosage (200mg/kg) group 4, and except that normal group, rat is processed the chronic kidney hypofunction model with 5/6 nephrectomy method; The right kidney of excision left side kidney 2/3, the one week back row excision second time first time, operation back one all beginning administrations for the second time, administering mode is gastric infusion or intraperitoneal injection; 4 weeks after the administration, 8 weeks, big respectively rathole frame was got blood, measured serum creatinine and blood urea nitrogen, and 4 weeks were put to death 5 after the administration; Off-test is put to death 10, does the pathology section, observes the pathological change of renal function.
Can find out from table 3, table 4 result, dosage in the astilbin intravenous injection (2.5mg/kg) group, astilbin is irritated stomach dosage (5mg/kg) group 1 and is reduced rat chronic renal failure serum creatinine and blood urea nitrogen (comparing p＜0.05 with model group); Prednisolone (12mg/kg) group; Astilbin intravenous injection heavy dose of (10mg/kg) group 1; Astilbin intravenous injection heavy dose of (25mg/kg) group 2, astilbin intravenous injection heavy dose of (50mg/kg) group 3, astilbin intravenous injection heavy dose of (100mg/kg) group 4; Astilbin is irritated stomach dosage (50mg/kg) group 2; Astilbin is irritated stomach dosage (100mg/kg) and is organized 3, and astilbin is irritated stomach dosage (200mg/kg) group 4 and obviously reduced rat chronic renal failure serum creatinine and blood urea nitrogen (comparing p＜0.01 with model group); Astilbin intravenous injection heavy dose of (50mg/kg) group 3 reduces rat chronic renal failure serum creatinine and blood urea nitrogen and astilbin intravenous injection heavy dose of (100mg/kg) group 4 relatively, there was no significant difference; Stomach dosage (100mg/kg) group 3 of irritating astilbin reduces rat chronic renal failure serum creatinine and blood urea nitrogen and astilbin and irritates stomach dosage (200mg/kg) group 4 relatively, there was no significant difference.
Pathological change: see that glomerule has compensatory hypertrophy in various degree under administration the 4th all model group light microscopics, proliferation of mesangial cells, mesentery substrate increases, and the glomerular capillary button loop is lobulated; Part glomerule blister cavities disappears, and the blood capillary tube wall thickens, and renal tubules swelling, expansion have proteinosis in the tube chamber; The little shrink tube of part, a matter has inflammatory cell infiltration, and each administration group is also seen above-mentioned change; But lesion degree is lighter, increases with dosage, and lesion degree alleviates; See proliferation of mesangial cells under administration the 8th all model group light microscopics, the substrate showed increased, the blood capillary tube wall subsides; The blood capillary segmented sclerosis, the harden zone many near blood vessel wall the circular PAS of the visible homogenizing wine-colored deposit that dyes in the hardened glomerule, indivedual glomerule have focal sacculus adhesion; Focal crescent forms, and a matter visible inflammatory cell soaks into, proliferation of fibrous tissue; Each organizes the glomerular sclerosis varying degree, increases with dosage, and lesion degree alleviates.
Table 3 astilbin is to the influence of kidney of rats excision chronic kidney hypofunction administration 4 all serum creatinines and blood urea nitrogen
Group dosage (mg/kg) serum creatinine (mg/dL) serum urea nitrogen (mg/dL)
Normal group---0.52 ± 0.05 6.45 ± 2.52
Model group--1.72 ± 0.19 22.54 ± 2.53
Prednisolone group 12 0.83 ± 0.13
*15.21 ± 3.25
*
1 1.62±0.18 21.12±2.40
2.5 1.53±0.15
* 19.95±2.20
*
10 1.29±0.31
** 16.90±4.09
**
Astilbin intravenous injection group 25 1.12 ± 0.24
*14.63 ± 3.25
*
50 1.02±0.19
** 13.39±2.45
**
100 1.01±0.33
** 12.85±3.88
**
5 1.55±0.16
* 20.21±2.22
**
Astilbin is irritated stomach group 50 1.42 ± 0.24
*18.60 ± 3.11
*
100 1.30±0.22
** 17.01±3.95
**
200 1.29±0.28
** 16.76±4.30
**
*, p＜0.05,
*, compare with model group p＜0.01
Table 4 astilbin is to the influence of kidney of rats excision chronic kidney hypofunction administration 8 all serum creatinines and blood urea nitrogen
Group dosage (mg/kg) serum creatinine (mg/dL) serum urea nitrogen (mg/dL)
Normal group---0.53 ± 0.08 6.05 ± 2.32
Model group--2.33 ± 0.26 28.98 ± 3.25
Prednisolone group 12 1.25 ± 0.17
*18.21 ± 4.25
*
1 2.19±0.22 27.15±3.09
2.5 2.06±0.21
* 25.65±2.57
*
10 1.75±0.37
** 21.73±5.26
**
Astilbin intravenous injection group 25 1.51 ± 0.32
*19.25 ± 3.19
*
50 1.39±0.26
** 15.07±3.45
**
100 1.37±0.44
** 14.85±3.88
**
5 2.09±0.22
* 25.98±2.72
**
Astilbin is irritated stomach group 50 1.92 ± 0.32
*23.91 ± 4.00
*
100 1.76±0.30
** 21.96±3.95
**
200 1.74±0.36
** 20.76±5.50
**
*, p＜0.05,
*, compare with model group p＜0.01
Test of the influence of 4 astilbins to one-sided ureter ligation kidney of rats interstitial fibrosis
4.1 material
Astilbin is by preparation example 1 and 6 preparations of preparation example
Laboratory animal regular grade Wistar rat, male, body weight 150-200g, the SD rat, Shandong greenery natural drug Societe Principia Research Development Experimental Animal Center provides qualifier: SYXK (Shandong) 20030020.
Benazepril, Novartis Pharma AG produces, lot number: 040306; The hydroxyproline test kit, biotech firm is built up in Nanjing, lot number: 050906.
4.2 test method and result
130 of rats, body weight 200-230g, 1 week of animal feeding; Each rat with 10% chloral hydrate 3.0mL/kg intraperitoneal injection of anesthesia after, the rat RAR is fixed on the operating-table, after the cropping with iodine tincture, 75% alcohol disinfecting field of operation; Row left side abdomen otch successively cuts skin, muscle and each layer of stomach wall, exposes and separation left side ureter; Wherein 10 rats are only cut abdominal cavity and free left side ureter, but not ligation with cut off, as sham operated rats; All the other 120 rats are with 4-0 silk thread ligation twice; Last one ligation point is positioned at left inferior pole of kidney level, between twice ligation point, cuts off ureter then, layer-by-layer suture; 120 modeling rats are divided into 12 groups at random; Be that model group, enalapril (10mg/kg) are organized, astilbin intravenous injection 1mg/kg organizes, astilbin intravenous injection 2.5mg/kg organizes, astilbin intravenous injection 25mg/kg organizes, astilbin intravenous injection 50mg/kg organizes, astilbin intravenous injection 100mg/kg organizes, astilbin filling stomach 2mg/kg organizes, astilbin filling stomach 5mg/kg organizes, astilbin filling stomach 50mg/kg organizes, astilbin filling stomach 100mg/kg organizes, astilbin filling stomach 200mg/kg organizes, each organized administration after 21 days, each treated animal of execution after 10% chloral hydrate anesthesia; Normal saline is left and taken left kidney after the lavation repeatedly, and nephridial tissue is fixed through 4% paraformaldehyde buffer.Cut an amount of nephridial tissue, press the explanation of hydroxyproline kit measurement and measure hydroxyproline.
Can find out from table 5 result; Astilbin intravenous injection 2.5mg/kg organizes, astilbin intravenous injection 25mg/kg organizes, astilbin intravenous injection 50mg/kg organizes, astilbin intravenous injection 100mg/kg organizes, astilbin filling stomach 5mg/kg organizes, astilbin filling stomach 50mg/kg organizes, astilbin filling stomach 100mg/kg organizes, astilbin filling stomach 200mg/kg organizes obvious reduction rat hydroxyprolin levels and (compares with model group; P＜0.05 or 0.01); Astilbin irritates stomach 100mg/kg group reduction hydroxyprolin levels and astilbin is irritated stomach 200mg/kg group relatively, there was no significant difference; Astilbin intravenous injection 50mg/kg group reduces hydroxyproline and astilbin intravenous injection 100mg/kg group compares there was no significant difference.
Routine pathology is learned and checked 1. macroscopy: sham operated rats kidney color is scarlet, smooth surface, peplos gloss, no adhesion.Other respectively organize the increase of kidney volume, and color is pale, and the surface is graininess, similar human body branny kidney, the adhesion of few regions kidney peplos.2. light microscopy checking: sham operated rats nephron clear in structure, glomerular capsule do not have expansion or dwindle, and renal cells does not have obvious degeneration and necrosis, do not have come off epithelial cell or cast, no vasodilation or cell infiltration in the matter in the tube chamber.The large stretch of renal tubular necrosis of model control group, the hyperplasia of kidney interstitial fibers, tubular ectasia, in a large amount of pale brown color refractive power materials or the downright bad epithelial cell that comes off are arranged, the glomerule decreased number, part glomerule fibrosis and with the adhesion of bag Man cyst wall, blister cavities disappears.Administration respectively organizes pathological changes and model control group is similar, but all has morphology in various degree to improve, and with heavy dose of each group of astilbin significantly, with model control group notable difference is arranged relatively especially.
Table 5 astilbin is to the influence of one-sided ureter ligation kidney of rats hydroxyproline content
Group dosage (mg/kg) hydroxyproline
(μg/g)
Sham operated rats---305 ± 56
Model group--760 ± 156
Benazepril group 12 487 ± 132
1 699±162
2.5 612±118
*
Astilbin vein 25 550 ± 87
*
Injection groups 50 533 ± 94
*
100 526±121
**
2 705±161
5 610±115
*
50 540±87
**
Astilbin is irritated stomach group 100 523 ± 94
*
200 518±121
**
P＜0.05,
*, compare with model group p＜0.01.
Claims (1)
1. astilbin is as the application of unique active component in the medicine of preparation treatment or prophylaxis of acute renal failure.
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