1.Effect of Simvastatin on Smad Protein Expression in Myocardial Infarction Rats
China Pharmacy 1991;0(05):-
OBJECTIVE:To investigate Smad3 and Smad7 expression in cardiac tissues in myocardial infarction (MI) rats and the effect of simvastatin (SIM) on expression of Smads.METHODS:36 rats were randomized into SIM (40 mg?kg-1,n=12) group,MI group (normal saline,n=12) and SHAM group (normal saline,n=12).Rats in first two groups were induced MI model.Rats of 3 groups were sacrificed after four weeks administration.The mRNA expressions of Smad3 and Smad7 in non-infarction regions were measured by RT-PCR.Smad3 and Smad7 protein expressions were measured by Western blotting assay.RESULTS:As compared with SHAM group,the expressions of Smad3 in MI group and SIM group were increased while the expressions of Smad7 were decreased.As compared with MI group,the mRNA expression and protein expression of Smad3 in SIM group was decreased while that of Smad7 increased (P
4.Astragalus injection' effect on the expression of hypoxia-inducible factor-1α and p53 in the retina of rats under hypoxia environment
Xiyu JIA ; Qin LIU ; Shu ZHANG ; Huiling BAI ; Wen DONG
Chinese Journal of Ocular Fundus Diseases 2016;32(4):423-427
Objective To observe the expression and mechanism of hypoxia-inducible factor-1α (HIF-1α) and p53 protein at the altitude of 5000 meter plateau hypoxia environment in rats,as well as the effect of Astragalus injection.Methods Sixty Sprague Dawley rats were randomly divided into the Astragalus injection intervention group and normal saline control group,30 rats in each group.Astragalus injection group rats were intraperitoneal injected of Astragalus injection (15 ml/kg) before 30 minutes into the plateau environment simulation cabin,normal saline group rats were intraperitoneal injected with the same volume of saline.30 minutes after injection,rats in each group were reared in the plateau experiment cabin which simulated altitude of 5000 m (oxygen partial pressure 11.3 kPa) for 2,6,8,12,24 hours,each time period of 6 rats.When get out,the rats were executed immediately and eyes were harvested.Retinal sections were studied by hematoxylin eosin stain,and immunohistochemical method for HIF-1α and p53 expression.Results For control rats,after 2 hours in the cabin,there was edema in retinal layers.HIF-1α and p53 were expressed mainly in the cytoplasm of retinal layers.When the periods in cabin extended,there was atrophy of retinal nerve fiber layer,swelling and degeneration of ganglion cells.The expression of HIF-1α and p53 was increased.Compared with the control group,the intervention group rat had similar but less severe retinal changes,and the expression of HIF-1α and p53 was significantly decreased (P <0.05).Conclusion Astragalus injection can reduce pathological retinal damage in rats at high altitude environment,and its mechanism may be associated with reduced HIF-1α,p53 expression.
5.Study on the Mechanism of Improvement Effects of Exenatide on Mitochondrial Function of H9c2 Cells un-der Hypoxia/reoxygenation Condition
Guanglei CHANG ; Jian LIU ; Shu QIN ; Dongying ZHANG
China Pharmacy 2016;27(10):1350-1353
OBJECTIVE:To study the mechanism of improvement effects of exenatide on mitochondrial function of H9c2 cells under hypoxia/reoxygenation (H/R) condition. METHODS:H9c2 cells were cultured in vitro and were divided into blank control group,drug control group(exenatide 200 nmol/L),model group(H/R),pretreatment group(exenatide 200 nmol/L+H/R),gluca-gon-like peptide-1 receptor (GLP-1R) inhibitor [Exendin-(9-39) 100 nmol/L+exenatide 200 nmol/L+H/R], cAMP inhibitor (Rp-cAMPS 1 μmol/L+exenatide 200 nmol/L+H/R)group and PKA inhibitor(H-895 μmol/L+exenatide 200 nmol/L+H/R)group. Except for first 2 groups,H/R model was established in other groups,and they were given exenatide 30 min before modeling and relevant inhibitor 10 min before giving exenatide. Morphology of mitochondria was observed by TEM,and mitochondrial calcium (Ca2+m)and the mitochondrial membrane potential(ΔΨm)were determined by flow cytometry. Cellular ATP content was measured by microplate reader. RESULTS:Compared with blank control group, mitochondrial cristae swelling was enhanced in model group,while density decreased,showing vacuolization;Ca2+m level increased while ΔΨm and ATP decreased (P<0.05). Com-pared with model group,mitochondrial cristae swelling relieved in pretreatment group,while density increased,showing vacuoliza-tion relieved;Ca2+m level decreased,while ΔΨm and ATP increased(P<0.05). Compared with pretreatment group,the levels of Ca2+m increased in 3 kinds of inhibitors group,while ΔΨm and ATP decreased(P<0.05). CONCLUSIONS:Exenatide attenuates H9c2 cell mitochondria Ca2+m accumulation,increases ΔΨm and ATP production. Which indicate its mechanism may be associated with activating GLP-1R/cAMP/PKA pathway.
6.Effect of simvastatin on left ventricular remodeling and heart function in rats with myocardial infarction
Dongying ZHANG ; Shu QIN ; Xianjun TANG ; Hui YANG
Chinese Pharmacological Bulletin 2003;0(07):-
Aim To study the effect of simvastatin(Sim) on left ventricular remodeling and heart function in rats with myocardial infarction(MI).Methods Myocardial infarction models were successfully induced by ligation of anterior descending coronary artery.24 h later the survivals were randomly divided into 3 groups.① MI group;② 20 mg Sim group(20 mg?kg~(-1)?d~(-1));③ 40 mg Sim group(40 mg?kg~(-1)?d~(-1)).The rats with sham ligation formed sham group.After 8 weeks,hemodynamic parameters,blood serum lipids,the ratio of RV and LV weight to body weight(RVWI,LVWI) were examined.The pathomorphological change and the collagen volume fraction(CVF) were analyzed by PSR dyeing.Results There were no significant differences in values of serum lipids among 4 groups.Compared with sham group,the left ventricular end-diastolic pressure(LVEDP) was increased and left ventricular systolic pressure(LVSP) was depressed significantly in MI group; the RVWI and LVWI and the CVF in border infarcted zone and Ⅰ/Ⅲ ratio were increased in MI group too.Compared with MI group,Sim partially normalized LVSP and LVEDP;abated ventricular weight index;reduced CVF in non-infarction zone in both Sim groups.Conculusion Simvastatin improves LV remodeling and heart function in rats with MI,which is associated with the effect of limiting myocardial hypertrophy and interstitial fibrosis.
7.Effect of simvastatin on interstitial remodeling in rats with myocardial infarction
Dongying ZHANG ; Shu QIN ; Xianjun TANG ; Hui YANG
Chinese Pharmacological Bulletin 1986;0(04):-
Aim To assess the effect of HMG-CoA inhibitors simvastatin on collagen remodeling in rats after myocardial infarction. Methods Myocardial infarction models were induced by ligation of anterior descending coronary artery. 24 hours later the survivals were randomly divided into 3 groups: (1) MI group; (2) 20 mg Sim group(20 mg? kg-1? d-1); (3) 40 mg Sim group(40 mg? kg-1? d-1). Rats with sham ligation formed into Sham group. After 8 weeks, the ratios of LV and RV weight to body weight (RVWI, LVWI) were examined and the collagen content was detected. The type Ⅰ and type Ⅲ collagen volume fraction (CVF) and Ⅰ/Ⅲ ratio in infarcted and non-infarcted zones were examined with PSR dyeing; also the mRNA expressions of type Ⅰ and type Ⅲ collagen in non-infarcted zone (NIZ) were detected with RT-PCR.Results Comparing with Sham group,the RVWI and LVWI in MI group increased significantly. The type Ⅰ CVF and type Ⅲ CVF in NIZ and the Ⅰ/Ⅲ ratio were increased in MI group. The mRNA expressions of type Ⅰ and type Ⅲ collagen in NIZ in MI group were higher than those in Sham group. Comparing with MI group, the RVWI and LVWI in both Sim groups were decreased significantly. The type Ⅰ CVF and type Ⅲ CVF in NIZ and the Ⅰ/Ⅲ ratio were depressed in both Sim groups, and the mRNA expressions of collagens were also lower than those in MI group, but higher than those in Sham group. Conculusion Simvastatin could attenuate the development of myocardial interstitial fibrosis in non-infarction zone to improve myocardial interstitial remodeling in rats after MI.
8.Simvastatin ameliorates rat ventricular remodeling after myocardial infarction:the role of phosphorylating extracellular signal-regulated kinase1/2
Xuelian XU ; Shu QIN ; Han LEI ; Qiang YE ; Maohui ZHANG
Chinese Pharmacological Bulletin 1987;0(02):-
Aim To study the effect of simvastatin on ventricular remodeling in rats after myocardial infarction,and the association between this effect and phosphorylating extracellular signal-regulated kinase1/2(p-ERK1/2).Methods Myocardial infarction(MI)rat models were successfully induced by ligation of anterior descending coronary artery.The treated rats were randomly divided into 4 groups(n=8~10):MI only group,MI plus 20 mg Sim group(20 mg?kg-1?d-1),MI plus 40 mg Sim group(40 mg?kg-1?d-1),and sham-operated group.After 4 weeks,the rats were checked by echocardiography including LVEDd,LVPWd,LVEF,FS,SV and CO.Myocardial p-ERK1/2 was also examined by immunohistochemistry and Western blot.Results Compared with sham-operated group,LVEDd,LVPWd in other groups were significantly increased(P
9.Effects of simvastatin on heme oxygenase-1 in acute myocardial infarction rats
Hongying CHEN ; Shu QIN ; Rui XIANG ; Dongying ZHANG
Chinese Pharmacological Bulletin 1986;0(04):-
Aim To investigate the changes of heme oxygenase-1(HO-1) in cardiomyocytes after acute myocardial infarction and the impact of simvastatin on HO-1 expression in rats.Methods Myocardial infarction models were made by anterior descending coronary artery ligation on male SD rats whereas sham group by spurious ligation.Survivals were randomized into myocardial infarction(MI) group,simvastatin(Sim) group and sham group 24 hours after the operation.The Sim group was treated with simvastatin 40 mg?kg-1?d-1 via gavage till sacrifice.MI and sham groups were gavaged with equal volume of 0.9% NaCl at the same time.Rats were sacrificed at time points of 24 hours,7 days and 28 days after the operation,for the detection of HO-1 mRNA by RT-PCR,HO-1 protein level by Western bolt,activity of superoxide dismutase(SOD) and content of malondialdehyde(MDA) by spectrophotometric method in non-infarcted zone.Results Expression of HO-1 mRNA and protein level increased at 24 hours,peaked at 7 days and decreased to basal levels at 28 days.All the indexes at each time point mentioned above were significantly higher in MI group than those in sham group.At the 7th day and 28 th day after the operation,the indexes were higher in Sim group than those in MI group(P
10.The experimental study of the benificial effects of simvastatin on ventricular remodeling induced by TGF?1 via Smad3 signal pathway
Xiangbin XIAO ; Shu QIN ; Dongying ZHANG ; Kanghua MA
Chinese Pharmacological Bulletin 1986;0(05):-
0.05).Compared with those in Sham group,LVWI,the typeⅠCVF,type Ⅲ CVF andⅠ/Ⅲ ratio in NIZ were increased significantly in MI group.Compared with those in MI group,the LVWI,the type ⅠCVF,type Ⅲ CVF andⅠ/Ⅲ ratio in NIZ were decreased significantly in Sim groups(but higher than those in Sham group).Compared with MI groups,left ventricular function in rats treated with simvastatin was also obviously improved.(2) Contrasted to those in MI group,the expressions of TGF-?1 and Smad3 were down-regulated in simvastatin treatment groups(but higher than those in Sham group).Conclusions Sim can ameliorate ventricular remodeling and ventricular function in rats induced by MI,and the mechanisms can be independent of its lipid-lowering and associated with inhibition of TGF-?1/Smad3 signal transduction.