CN107050003A - Bakuchiol is used for the application for preparing infectious myocardial damage medicine - Google Patents
Bakuchiol is used for the application for preparing infectious myocardial damage medicine Download PDFInfo
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Abstract
It is used for the application for preparing infectious myocardial damage medicine the invention discloses Bakuchiol.Inventor by isolated cells and body animal confirm, Bakuchiol can concentration dependent the proinflammatory inflammation factor level of reduction, recover cardiomyocyte viability, reduce cardiomyocyte apoptosis rate, play significantly anti-inflammatory and anti-cardiomyocyte apoptosis effect；Cardiac muscular tissue's destruction and cell infiltration are reduced, cardiomyocyte apoptosis rate is reduced, mitigates endoplasmic reticulum stress response, stronger anti-inflammatory, anti-myocardial necrosis and apoptosis is played, improves the effect of cardiac systolic function, there is good potential applicability in clinical practice.
Description
Technical field
The present invention relates to application of the Bakuchiol in treating and preventing heart disease, more particularly to Bakuchiol is being controlled
Treat or prevent bacillary intimitis, cardiac muscle caused by bacteremia or septicopyemia etc. caused by systematicness or other organs infection
One or more kinds of applications in inflammatory lesion myocardial damage.
Background technology
Bakuchiol is the monoterpene vinyl compound extracted from legumes psoraleae fruit, is lived with extensive pharmacology
Property.Research shows that Bakuchiol has antibacterial activity, antitumor activity, antiinflammation, hypoglycemic effect for reducing blood fat, anti-oxidant work
Property, antidepression, phytoestrogen sample effect etc..
The content of the invention
Inventor is by septicemia cell model and observes inflammation and the discovery of myocardial damage indices, and Bakuchiol can be dense
The reduction il-1 (IL-1) and tumor necrosis factor-alpha (TNF-α) level of dependence are spent, recovers cardiomyocyte viability, is reduced
Cardiomyocyte apoptosis rate, plays significantly anti-inflammatory and the effect of anti-cardiomyocyte apoptosis；Pass through septicemia animal model, it was demonstrated that Bakuchiol can be dense
Reduce IL-1 in mice serum, TNF-α, lactic dehydrogenase 1 (LDH1) and creatine kinase isozyme (CK-MB) water to degree dependence
It is flat, Left Ventricular Ejection Fraction (LVEF%) and left LVSF (LVFS%) value is improved, cardiac muscular tissue's destruction is reduced thin with inflammation
Born of the same parents infiltrate, and reduce cardiomyocyte apoptosis rate, play stronger anti-inflammatory, anti-myocardial necrosis and apoptosis, improve the effect of cardiac systolic function.
Research shows, the stronger anti-inflammatory of Bakuchiol, anti-myocardial necrosis and apoptosis, improves the effect of cardiac systolic function, has very well
Potential applicability in clinical practice.
It is used to prepare infectious myocardial damage medicine or protectant application the invention provides Bakuchiol.
The medicine or protective agent of the present invention is intravenous injection drug-delivery preparation.
The medicine or protective agent dosage of the present invention is per kg body weight 25mg-100mg.
Advantages of the present invention：
1st, Bakuchiol can suppress cardiac muscle cell apoptosis caused by inflammation, with anti-inflammatory Anti-G value.
2nd, Bakuchiol can suppress myocardial damage caused by inflammation, improve heart function, improve cardiac systolic function.
3rd, Bakuchiol can activate Sirt1 signal paths, reduce endoplasmic reticulum stress response, less cardiac muscle cell apoptosis,
Protect cardiac muscle cell.
Brief description of the drawings
Fig. 1 is influences of the various concentrations BAK to the LPS myocardial cell injury modeled inflammation factors and cell viability.(A) it is different
IL-1 and TNF-α concentration in the BAK processing septicopyemia cell model wild Oryza species of concentration；(B) the BAK processing of various concentrations
Cytoactive after septicopyemia cell model, OD values are absorbance.As a result represented with mean ± standard deviation, n=6.With
Control groups compare a P<0.05, aa P<0.01, aaa P<0.001；Compared b P with LPS groups<0.05, bb P<0.01, bbb
P<0.001；Compared c P with 1 μM of+LPS group of BAK<0.05, cc P<0.01, ccc P<0.001；Compared with 5 μM of+LPS groups of BAK
d P<0.05, dd P<0.01.
Fig. 2 is influences of the various concentrations BAK to LPS myocardial cell injury model cell apoptosis.As a result with mean ± standard
Difference expression, n=6.Compared a P with Control groups<0.05, aa P<0.01, aaa P<0.001；Compared b P with LPS groups<
0.05, bb P<0.01, bbb P<0.001；Compared c P with 1 μM of+LPS group of BAK<0.05, cc P<0.01, ccc P<0.001；
Compared d P with 5 μM of+LPS groups of BAK<0.05, dd P<0.01.
Fig. 3 is mouse heart function after various concentrations BAK processing.(A) mouse echocardiogram after various concentrations BAK processing.
(B) mouse left ventricular LV EF% and LVFS% after various concentrations BAK processing.As a result represented with mean ± standard deviation, n=20.With
Control groups compare a P<0.05, aa P<0.01, aaa P<0.001；Compared b P with LPS groups<0.05, bb P<0.01, bbb
P<0.001；Compared c P with BAK 25mg/kg+LPS groups<0.05, cc P<0.01；Compared d P with BAK 50mg/kg+LPS groups<
0.05。
Fig. 4 is mice serum inflammatory factor level and LDH-1, CK-MB level after various concentrations BAK processing.(A) mouse blood
Clear TNF-α level (B) mice serum IL-1 levels (C) mice serum LDH-1 level (D) mice serums CK-MB.As a result with mean
± standard deviation represents, n=20.Compared a P with Control groups<0.05, aa P<0.01, aaa P<0.001；Compared b with LPS groups
P<0.05, bb P<0.01, bbb P<0.001；Compared c P with BAK 25mg/kg+LPS groups<0.05, cc P<0.01；With BAK
50mg/kg+LPS groups compare d P<0.05,dd P<0.05.
Fig. 5 is that mouse cardiac muscle HE is dyed and visual field inner cell check figure after various concentrations BAK is handled, multiplication factor 200 ×.Knot
Really represented with mean ± standard deviation, n=5.Compared a P with Control groups<0.05, aa P<0.01, aaa P<0.001；With LPS
Group compares b P<0.05, bb P<0.01；Compared c P with BAK 25mg/kg+LPS groups<0.05, cc P<0.01；With BAK
50mg/kg+LPS groups compare d P<0.05,dd P<0.05.
Fig. 6 is that mouse cardiac muscle level of apoptosis is detected after various concentrations BAK is handled, multiplication factor 400 ×.As a result with mean ±
Standard deviation represents, n=5.Compared a P with Control groups<0.05, aa P<0.01, aaa P<0.001；Compared b P with LPS groups<
0.05, bb P<0.01；Compared c P with BAK 25mg/kg+LPS groups<0.05, cc P<0.01；With BAK 50mg/kg+LPS groups
Compare d P<0.05,dd P<0.05.
Fig. 7 is mouse SIRT1 paths, ERS and apoptosis-related protein expression after various concentrations BAK processing.All numbers
Change according to the multiple for being expressed as Control groups, as a result represented with mean ± standard deviation, n=6.Compared a P with Control groups<
0.05, aa P<0.01, aaa P<0.001；Compared b P with LPS groups<0.05, bb P<0.01, bbb P<0.001；With BAK
25mg/kg+LPS groups compare c P<0.05, cc P<0.01, ccc P<0.01；Compared d P with BAK 50mg/kg+LPS groups<
0.05,dd P<0.05。
Embodiment
Infectious myocardial damage of the present invention, is particularly 1. bacterial endocarditis；2. systematicness or other are dirty
Myocardium inflammatory lesion caused by bacteremia caused by device infection；3. caused by septicopyemia caused by systematicness or other organs infect
Myocardium inflammatory lesion.
The present invention is further elaborated by the following examples.Embodiment is that the present invention is described in detail, but
The present invention is not by these any restriction.
Bakuchiol used is tested below and is purchased from Dalian U.S. logical sequence Technology Co., Ltd., and purity is HPLC >=98%.
Embodiment 1:Inventor's research finds that Bakuchiol can mitigate the myocardium primary cell inflammatory reaction of LPS inductions,
Reduce Apoptosis.
Scheme：
Myocardium primary cell is handled using LPS, causes the model of myocardial damage in cellular level simulation bacterial myocarditis,
Various concentrations Bakuchiol is given to be handled.
Step：
1) separation of rat heart muscle primary cell and culture：SD rat suckling mouse ventricular sections are taken under aseptic condition, after PBS rinsings
It is cut into 0.5mm2Fritter, add the digestion of II Collagenase Types, collect cell, centrifugation.Gained cell is placed in containing 10% tire ox blood
In clear DMEM culture mediums, the adherent 60-90min in 37 DEG C, 5%CO2 incubators, differential velocity adherent removes adherent cardiac muscle into fibre
Cell is tieed up, the culture plate culture that media transfer to gelatin is treated adds BrdU in first 3 days and suppresses fibroblastic growth,
Obtain cardiac muscle cell.Observed under inverted microscope, it is seen that cell there are rhythm and pace of moving things spontaneous contractions in the visual field, randomly selects 5
The visual field is counted, can spontaneous contractions cells on total cells number more than 95% can be considered and obtain purer primary cardiomyocytes.
2) cell model builds and is administered：Gained cardiac muscle primary cell shifts to an earlier date 12h each groups and uses isometric serum-free DMEM/
F12 culture mediums change liquid, and sterile saline dissolving LPS is made 20ug/ml mother liquors, given according to 100ng/ml final concentration
Medicine, coprocessing 12h.Bakuchiol group is given, pretreatment 4h is given according to 1uM, 5uM, 10uM concentration.After the completion of pretreatment, inhale
Abandon culture medium, the isometric culture medium of LPS concentration such as addition and LPS groups.Drawn materials and detected jointly after 12h.
3) CCK-8 methods detection cytoactive：The myocardial cell suspensions that differential velocity adherent is completed are inoculated in 96 orifice plates, and control is per hole
Cell number is between 10000-12000, to be observed after 48h and change liquid；After each group processing, careful inhale abandons each hole supernatant, 37 DEG C
PBS is washed 2 times；Under the conditions of lucifuge, according to 10：1 proportional arrangement DMEM/F12 and CCK-8 reagent mixed liquors, 110ul is added per hole
Mixed liquor；After 37 DEG C/5%CO2 cell incubator cultures 2h, each hole absorbance at 450nm is detected using ELIASA；Each group OD values
It is proportional with cell viability.
4) ELISA method detection cell culture medium IL-1 and TNF-α level：Each group cell culture medium is collected, in 4 DEG C of centrifuges
In with 12000rpm centrifuge 15 minutes, to remove the impurity such as cell fragment, carefully draw supernatant；Illustrate according to ELISA kit
Book requirement, configures each working solution, and blank well, standard control hole and testing sample hole are set respectively, and two secondary orifices are all provided with per hole；
100ul various concentrations standard items and culture medium to be measured are added in hole successively according to explanation, blank well adds isometric standard items
Dilution；37 DEG C of water-baths 90 minutes；Liquid in hole is gently dried, 100ul biotinylated antibody working solutions are added per hole, covering is new
Enzyme mark version film, 37 DEG C are incubated 60 minutes；Get rid of in hole liquid and firmly patted dry on blotting paper；After patting dry, added per hole
100ul enzyme combination working solutions, covering enzyme mark version film, 37 DEG C are incubated 30 minutes；Liquid in hole is abandoned in suction, after drying, is used per hole
350ul cleaning solutions board-washing 6 times X2 minutes, gets rid of in hole liquid and is firmly patted dry on blotting paper；100ulTMB hairs are added per hole
Light substrate working solution adds terminate liquid and terminates reaction；The extinction that each hole of enzyme mark version goes out in 450nm is detected with ELIASA；According to standard
Product concentration gradient and respective absorbance computer fitting standard curve, calculate the respective concentration of each testing sample.
5) TUNEL detects Apoptosis：Differential velocity adherent myocardial cell suspensions, are inoculated in laser confocal microscope special
Cell model is built after ware, 48h, and processing is administered according to each group scheme；After the completion of processing, culture medium is discarded, ware is put
In on horizontal shaker, PBS is washed, 60rpm, 5 minutes；PBS is abandoned in suction, and cell, 30-60 are fixed using 4% paraformaldehyde
Minute；PBS washed once, 60rpm, 5 minutes；Add 0.1%Triton X-100 solution and carry out Cell-transmission model, be placed in
5 minutes on ice；TUNEL reaction solutions are configured according to kit specification, No. 1 liquid and No. 2 liquid allocation ratios are 1:9, added per ware
200ul, 37 DEG C of lucifuges are incubated 2 hours.Subsequent step all should be at lucifuge condition；Dyeing is finished, using PBS in level
Washed three times on shaking table, 90rpm, 5 minutes；PBS is abandoned in suction, using DAPI dyes cores, and 200ul, incubation at room temperature 15 are added per ware
Minute；Dyeing is finished, and is washed using PBS on horizontal shaker three times, 90rpm, 5 minutes；Laser copolymerization is used immediately
Focusing microscope high power Microscopic observation fluorescence, randomly selects 5 visuals field and counts apoptotic cell check figure, calculating myocardium apoptosis rate.
As a result：
IL-1 and TNF-α content as shown in Figure 1A, are given after BAK pretreatments, training can be observed in each group cell culture medium
IL-1 in nutrient solution, the reduction of TNF-α content (compared with LPS groups, P<0.05), prompting rat cardiac ventricular myogen subtracts for cellular inflammation reaction
Gently.Simultaneously it is observed that IL-1, TNF-α content reduction amplitude increase as BAK administration concentrations are raised in nutrient solution, carry
Show in 10uM dosage, BAK antiinflammatory actions and drug dose are proportionate (P<0.05).
Cell viability detection is given after BAK pretreatments as shown in Figure 1B, and cell viability has substantially recovered (with LPS group phases
Than P<0.05), with the increase of BAK dosages, the myocardial viability for showing concentration dependent recovers trend (P<0.05), but
It is still below control groups (P<0.05).
Apoptosis TUNEL coloration results are as shown in Fig. 2 give after BAK pretreatments, Apoptosis ratio is substantially reduced
(compared with LPS groups, P<0.05), each administration group group apoptosis rate is below control groups (P<0.05).The reduction amplitude of apoptosis is also
With BAK dosage positive correlations (P<0.05), prompting BAK shows the anti-cardiomyocyte apoptosis work(of concentration dependent in 10uM dosage
Energy.
Embodiment 2：Inventor's research finds that Bakuchiol can mitigate the mouse cardiac muscle inflammation of LPS inductions, improves heart work(
Can, reduce cardiac muscle cell apoptosis.
Scheme：
Mouse cardiac muscle damage model is set up using injection LPS, causes myocardium damage in animal level simulation bacterial myocarditis
The model of wound, gives various concentrations Bakuchiol and is handled.
Step：
1) Animal Model：12 weeks healthy male C57BL/6 mouse, are injected intraperitoneally according to 10mg/kg body weight
LPS, 6 as a child row ultrasound detections.For needing to give Bakuchiol group, first 5 days are administered according to 25mg/kg, 50mg/ in LPS
Kg, 75mg/kg, 100mg/kg dosage give Bakuchiol intraperitoneal injection daily, and last time administration is 40 points before lps injection
Clock.Using Vevo high-resolution toy ultrasonic image system detectio mouse heart functions, carry analysis software using system and calculate
Mouse LVEF% values and LVFS% values.
2) histone is extracted：Left ventricular tissues are taken, the PBS of 0.5ml precoolings is added；Tissue block is shredded to 1mm3
Most of supernatant is abandoned in size, suction, is added 1ml PBSs and is washed one time, 4 DEG C, 3000rpm centrifugations 3min；Supernatant is abandoned in suction,
The potent lysates of 2400ul, 300ul inhibitors of phosphatases and 300ul protease inhibitors are added, is inserted using tissue grinder
Each EP pipes tissue abrasion, cracks 20 minutes after standing on ice；4 DEG C, 12000rpm centrifuges 20 minutes protein quantifications.
3) cardiac muscular tissue HE is dyed：Apex is slowly injected into containing heparin-saline, and the liquid of right auricle of heart outflow is changed into
When bright, perfusion liquid is replaced with into 4% paraformaldehyde fixer；After paraformaldehyde tissue is fixed successfully, cut along heart root
Each blood vessel, completely removes heart.Heart is put into 4% paraformaldehyde, it is fixed at least 24 hours after progress；FFPE, cut
Piece with dewaxing (in sequence successively in 30%, 50%, 70%, 80%, 95%, 95%, 100% ethanol soak 40 minutes, then
According to 100% ethanol, 100% ethanol/dimethylbenzene 1:1 mixed liquor, xylene concentration gradient, which are soaked 30 minutes, carries out tissue dewatering
It is transparent；According to dimethylbenzene/soft wax 1:1 30 minutes, soft wax 55 minutes, the order of hard wax 50 minutes carry out the saturating wax embedding of tissue；Cut
Piece, setting slice thickness is 5um, and section is affixed on poly-D-lysine overlay film slide using piece method is dragged for, after 70 DEG C of roasting piece 1h,
60 DEG C of roasting piece 5h；Section is placed in dimethylbenzene and soaked 10 minutes, dimethylbenzene is changed and soaks again 10 minutes, according to 100%,
100%th, 95%, 95%, 80%, 70%, 50%, 30% ethanol, the order of deionized water soak dewaxing in 2 minutes to water successively,
In case dyeing.)；Section immersion haematoxylin dye liquor (is dyed 30 seconds 2 minutes, softly rushed using running water by cardiac muscular tissue HE dyeing
Wash 3 minutes；Immerse 1% acidic alcohol 30 seconds, 1% ammoniacal liquor 10 seconds decolourizes, and is softly rinsed using running water 6 minutes；Immerse Yihong
Dye liquor is dyed 1 minute, is softly rinsed using running water 6 minutes；According to 70%, 80%, 95%, 95%, 95%, 100%,
100% concentration gradient ethanol, dimethylbenzene, dimethylbenzene soak 2 minutes respectively carries out dehydration transparent processing；Neutral gum mounting.)
4) cardiac muscular tissue TUNEL is dyed：It will dewax to water section and washed with PBS 3 times, 60rpm, every time 5 points
Clock；PBS is got rid of, is punched using 0.1%Triton-100 solution, 10 minutes time；Washed and punched using PBS
The histotomy finished 3 times, 60rpm, every time 5 minutes；Configure TNUEL dye liquors, every dropwise addition 50ul, 37 DEG C of water-bath 2h dyeing；
Dyeing is finished, and PBS is washed 3 times, 60rpm, every time 10 minutes；50ul DAPI dye liquors are added dropwise and redye nucleus, 37 DEG C of water
Bath 10 minutes；Dyeing is finished, and PBS is washed 3 times, 60rpm, every time 10 minutes；Using 50% glycerine mounting, 4 are positioned over
In DEG C environment overnight.Fluorescence is observed under next day laser confocal microscope, blueness is nucleus, and be that apoptotic cell contaminates at green 2 points
Color, randomly selects 5 visuals field and counts apoptotic cell check figure, calculating myocardium apoptosis rate.
5) cytokines measurement：Inflammatory factor IL-1 and TNF-α level are using the detection of foregoing ELISA method, LDH1 and CK-
MB levels are detected using automatic clinical chemistry analyzer.
As a result：
The Assessment of Left Ventricular Systolic Function of mouse, as shown in Figure 3.Give after intraperitoneal injection BAK pretreatments, BAK 25mg/kg+
LPS groups, BAK 50mg/kg+LPS groups, BAK 75mg/kg+LPS groups, BAK 100mg/kg+LPS groups show heart contraction
The improvement of function, and left ventricular LV EF%, LVFS% value rebound significantly (compared with LPS groups, P<0.05), prompting BAK can be certain
Degree recovers left systolic heart.On tri- dosage of BAK concentration 25mg/kg, 50mg/kg, 75mg/kg, LVEF%, LVFS%
Value shows the elevated trend (P of gradient<0.05), but it is below control groups (P<0.05), in BAK concentration 75mg/kg and
Between 100mg/kg and there was no significant difference (P>0.05).
Mice serum inflammatory factor level gives BAK intervention groups it is observed that serum levels of inflammatory cytokines as shown in Fig. 4 A＆B
Level substantially reduces (P<0.05).The positive dependence drop of dosage is presented between tri- groups of BAK concentration 25mg/kg, 50mg/kg, 75mg/kg
Low (P<0.05) but control groups (P is remained above<0.05), likewise, serum is scorching between BAK75mg/kg and BAK100mg/kg groups
Sex factor and no significant difference.
The horizontal 4C＆D of mice serum Myocardial Damage Index LDH1, CK-MB, give BAK intervention groups, serum cardiac necrosis identification
Being decreased obviously occurs in thing LDH1 and CK-MB (to be compared, P with LPS groups<0.05), or even in BAK75mg/kg and BAK100mg/kg concentration
Under close to control group mouse physiological level (P<0.05).And in tri- groups of BAK concentration 25mg/kg, 50mg/kg, 75mg/kg
Between dosage positive correlation is presented, each index value is close between BAK75mg/kg and BAK100mg/kg groups, and no significant difference.
Murine myocardium HE coloration results show (Fig. 5), give the visible myocardial tissue structure of HE dyeing after BAK relatively clear
It is clear, and the reduction of visual field inner cell nuclear volume (compared with LPS groups, P<0.05), capilary monocyte infiltration is reduced between myocyte.It is single
For the inner cell nuclear volume of the visual field, had no between BAK25mg/kg and 50mg/kg, between BAK75mg/kg and 100mg/kg bright
Different (the P of significant difference>0.05).But two groups of visual field inner cell nuclear volumes of BAK25mg/kg, 50mg/kg are still significantly higher than BAK75mg/
Two groups of (P of kg, 100mg/kg<0.05).
Mouse cardiac muscle apoptosis TUNEL dyeing (Fig. 6) display, can be observed in BAK pretreated groups, dense in BAK 75mg/kg
Within degree, as dosage increases, the reduction (P of gradient is presented in apoptosis rate<0.05), but remain above
Control groups (P<0.05).And in BAK100mg/kg concentration, cardiomyocyte apoptosis rate do not show continuation downward trend (with
BAK 75mg/kg+LPS groups compare, P>0.05).
Embodiment 3:Inventor's research finds that Bakuchiol can activate classical myocardial preservation path：SIRT1 signal paths,
Er stress (ERS) is reduced, cardiac muscle cell apoptosis is reduced.
Scheme：
Mouse cardiac muscle damage model is set up using injection LPS, causes myocardium damage in animal level simulation bacterial myocarditis
The model of wound, gives various concentrations Bakuchiol and is handled, myocardial preservation path is detected.
Step：
Abovementioned steps are shown in Animal Model and administration.Auricle and right ventricle are peeled off, only retains left ventricle, tissue egg is carried out
It is white to extract.Western detects SIRT1 signal paths and ERS and apoptosis-related protein expression.
As a result：
LPS groups shown in Fig. 7 is compared with Control groups, and (P is lowered in SIRT1 expression<0.001), AC-FOXO1 is raised downstream
(P<0.001).ERS path PERK/eIF2 α phosphorylations increase (equal P<0.001), ATF4/CHOP is activated (ATF4 downstream
Level, P<0.001；CHOP levels, P<0.01) pro apoptotic protein Bax raises (P<0.001)；Anti-apoptotic proteins Bcl-2 lowers (P
<0.001).Give after Bakuchiol processing, SIRT1 expression has been raised (to be compared, BAK 25mg/kg+LPS groups P with LPS groups<
0.05, remaining group of P<0.01), but less than Control groups (BAK 25mg/kg+LPS groups P<0.001, BAK 50mg/kg+LPS groups P<
0.01, remaining group of P<0.05)；AC-FOXO1 is lowered downstream (compares, BAK 25mg/kg+LPS groups and BAK 50mg/kg+ with LPS groups
LPS groups P<0.05, remaining group of P<0.01), (compare higher than Control groups with LPS groups, BAK 25mg/kg+LPS groups and BAK 50mg/
Kg+LPS groups P<0.01, remaining group of P<0.05)；The reduction of ERS path PERK phosphorylation levels (is compared, BAK 25mg/kg+ with LPS groups
LPS groups and BAK 50mg/kg+LPS groups P<0.05, remaining administration group P<0.01), eIF2 α phosphorylation levels reduction (with LPS groups ratio,
BAK 25mg/kg+LPS groups and BAK 50mg/kg+LPS groups P<0.05, BAK 100mg/kg+LPS group groups P<0.01, BAK
75mg/kg+LPS groups P<0.001), ATF4 horizontal down-regulations (compare, BAK 25mg/kg+LPS groups P with LPS groups<0.05, remaining administration group
P<0.01), CHOP is only in BAK 50mg/kg+LPS groups (P<0.05), BAK 75mg/kg and BAK 100mg/kg groups (P<0.01)
There is notable rise.Pro apoptotic protein Bax is lowered (to be compared, BAK 25mg/kg+LPS groups and BAK 50mg/kg+LPS groups P with LPS groups<
0.05, remaining administration group P<0.01), anti-apoptotic proteins Bcl-2 up-regulations (are compared, BAK 25mg/kg+LPS groups (P with LPS groups<0.05),
BAK 50mg/kg+LPS groups P<0.01, remaining administration group P<0.001), Bcl-2 is in BAK 100mg/kg dosage and 75mg/kg dosage
Group expression quantity is higher than Control groups (P<0.05).Above-mentioned albumen variation tendency shows dose-dependant within 75mg/kg dosage
Property (between adjacent sets compare P<0.05, P<0.01 or P<0.001), the above-mentioned egg between 100mg/kg dosage and 75mg/kg dosage
Equal no significant difference (the P of leucismusization>0.05).Bakuchiol can adjust inflammation by recovering SIRT1 levels, mitigate endoplasmic reticulum
Stress, Apoptosis is reduced, myocardium protecting action is played.
Claims (6)
1. Bakuchiol is used for the application for preparing infectious myocardial damage medicine.
2. application as claimed in claim 1, it is characterised in that described medicine is intravenous injection drug-delivery preparation.
3. application as claimed in claim 1, it is characterised in that described drug administration dosage is per kg body weight 25mg-
100mg。
4. Bakuchiol is used to prepare the protectant application of infectious myocardial damage.
5. application as claimed in claim 3, it is characterised in that described protective agent is intravenous injection drug-delivery preparation.
6. application as claimed in claim 1, it is characterised in that described protective agent dosage is per kg body weight 25mg-
100mg。
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112121042A (en) * | 2020-09-22 | 2020-12-25 | 西北大学 | Application of PSO in preparation of anti-septicemia and myocardial damage drug induced by anti-septicemia |
| CN113230356A (en) * | 2021-05-07 | 2021-08-10 | 陕西健驰生物药业有限公司 | Application of radix puerariae and celery soup in preparation of nutritional food for resisting septicemia and myocardial damage |
| CN113855655A (en) * | 2021-09-22 | 2021-12-31 | 上海市静安区中心医院(复旦大学附属华山医院静安分院) | Application of bakuchiol in preparation of medicine for treating acute myocardial infarction |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112121042A (en) * | 2020-09-22 | 2020-12-25 | 西北大学 | Application of PSO in preparation of anti-septicemia and myocardial damage drug induced by anti-septicemia |
| CN112121042B (en) * | 2020-09-22 | 2021-11-16 | 西北大学 | Application of PSO in preparation of anti-septicemia and myocardial damage drug induced by anti-septicemia |
| CN113230356A (en) * | 2021-05-07 | 2021-08-10 | 陕西健驰生物药业有限公司 | Application of radix puerariae and celery soup in preparation of nutritional food for resisting septicemia and myocardial damage |
| CN113855655A (en) * | 2021-09-22 | 2021-12-31 | 上海市静安区中心医院(复旦大学附属华山医院静安分院) | Application of bakuchiol in preparation of medicine for treating acute myocardial infarction |
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Application publication date: 20170818 |