Effect of oxymatrine on myocardial fibrosis in mouse with diabetic cardiomyopathy and its mechanism
Objective To study the effects of oxymatrine(OMT)on myocardial fibrosis(MF)in mice with diabetic cardiomyopathy(DCM)induced by a high-fat high-sugar diet(HFD)combined with streptozotocin(STZ)and the mechanism.Methods A total of 61 C57BL/6 mice were divided into a control group(n=12,normal chow),and an HFD group(n=49,high-fat high-sugar diet).After 12 weeks of feeding,insulin resistance testing and intraperitoneal glucose tolerance tests(IPGTT)were conducted on the mice.The mice with insulin resistance and glucose tolerance abnormalities were intraperitoneally injected with a dose of 30 mg/kg STZ.The injection was administered once every two days for a total of four injections.One week later,the mice with fasting blood glucose(FBG)≥11.1 mmol/L were considered to have successfully modeled type 2 diabetes mellitus.The successfully modeled HFD group mice were randomly divided into the following groups:model group(n=13,DCM group),OMT-L group(n=13,low-dose OMT,25 mg/kg),OMT-H group(n=12,high-dose OMT,50 mg/kg),Met group(n=11,metformin,250 mg/kg).Control and DCM groups were gavaged with normal saline,while the rest of the groups were gavaged with corresponding medicines.The intervention lasted for two months during which fasting blood glucose(FBG)was monitored.A small animal ultrasound system was used to examine mouse left ventricular ejection fraction(EF)and fractional shortening rate(FS％)in each group.Assay kits were used to measure the levels of mouse serum cholesterol(CHO),triglycerides(TGs),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)in each group.Hematoxylin and Eosin(HE)staining and Masson's trichrome staining were performed to observe mouse histopathological characteristics and collagen deposition in myocardial tissues of each group.Western blot was applied to detect mouse MF-related proteins[α-smooth muscle actin(α-SMA),collagen type Ⅰ(Collagen Ⅰ),collagen type Ⅲ(Collagen Ⅲ),and fibronectin(FN)]and silent information regulator 1(SIRT1)in myocardial tissues in each group.Immunohistochemical(IHC)staining was used to examine the protein expressions of α-SMA and SIRT1 in mouse myocardial tissues.Results FBG level in OMT-H group was significantly lower than that in DCM group(P＜0.05),while EF and FS％were higher than those in DCM group(P＜0.05).The levels of mouse serum T-CHO,TGs,and LDL-C in OMT group were significantly less than those in DCM group(P＜0.05),while HDL-C content was higher than that in DCM group(P＜0.05).When compared to DCM group,the mice in OMT group showed normal cellular morphology and reduced collagen deposition area in myocardial tissues.The expressions of MF-related proteins in myocardial tissues in OMT group were decreased when compared to DCM group(P＜0.05).In contrast,SIRT1 protein expression was increased when compared to DCM group(P＜0.05).IHC results show that α-SMA protein expression in the myocardial tissue was decreased but SIRT1 protein was increased in OMT group when compared to DCM group(P＜0.05).Conclusion OMT improves MF in mice with diabetes,and its mechanism of action might be related to regulating the SIRT1 signal.
diabetes mellitus,type 2diabetic cardiomyopathyfibrosisoxymatrinemyocardial fibrosishigh-fat and high-glucose dietstreptozotocinsilent information regulator 1
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