芍药苷对2型糖尿病模型大鼠心肌损伤的改善作用及机制研究
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篇名: 芍药苷对2型糖尿病模型大鼠心肌损伤的改善作用及机制研究
TITLE: Study on Improvement Effects and Mechanism of Paeoniflorin on Myocardial Injury in Type 2 Diabetic Model Rats
摘要: 目的:研究芍药苷对2型糖尿病(T2DM)模型大鼠心肌损伤的改善作用及机制。方法:实验设置正常组、模型组、阳性对照组(二甲双胍90mg/kg)和芍药苷高、中、低剂量组(90、60、30mg/kg),每组8只大鼠。除正常组外,其余各组大鼠均通过饲以高糖高脂饲料+腹腔注射链脲佐菌素(30mg/kg)的方法建立T2DM模型。造模成功后,各给药组大鼠灌胃相应药液,正常组和模型组大鼠灌胃等体积生理盐水,每天1次,连续4周。测定大鼠体质量、空腹血糖值并进行口服葡萄糖耐量实验;测定大鼠血清中糖化血清蛋白(GSP)、总胆固醇(TC)、三酰甘油(TG)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肌酸激酶同工酶MB(CK-MB)、肌钙蛋白Ⅰ(cTnⅠ)水平,观察大鼠心肌组织病理形态学变化,检测大鼠心肌细胞凋亡指数,并分别采用免疫组化法和Westernblot法检测大鼠心肌组织中B细胞淋巴瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)、胱天蛋白酶3(caspase-3)蛋白表达水平。结果:与正常组比较,模型组大鼠体质量和血清中GSH-Px、SOD水平以及心肌组织中Bcl-2蛋白表达水平均显著降低(P<0.01),空腹血糖值、血糖曲线下面积、血清中生化指标(GSP、TC、TG、MDA、CK-MB、cTnⅠ)水平、心肌细胞凋亡指数和心肌组织中Bax、caspase-3蛋白表达水平均显著升高或增加(P<0.05或P<0.01);心肌组织排列相对不规则,部分肌纤维断裂。与模型组比较,除芍药苷低剂量组大鼠体质量和血清中SOD、MDA水平以及心肌组织中Bax蛋白表达水平外,芍药苷各剂量组大鼠的上述指标水平均得到显著回调(P<0.05或P<0.01)。结论:芍药苷可调节T2DM模型大鼠的糖脂代谢、增强其抗氧化能力、抑制其心肌细胞凋亡,对其心肌损伤具有一定的改善作用;该作用的分子机制可能与上调心肌组织中Bcl-2蛋白表达,下调心肌组织中Bax、caspase-3蛋白表达有关。
ABSTRACT: OBJECTIVE:To study the improvement effects of paeon iflorin(PF)on myocardial injury in type 2 diabetes mellitus(T2DM)model rats and its mechanism. METHODS :The experiment was set up in the normal group ,model group , positive control group (metformin 90 mg/kg),PF high-dose ,medium-dose and low-dose groups (90,60,30 mg/kg),with 8 rats in each group. Except for normal group ,other groups were given high-glucose and high-fat diet and intraperitoneal injection of streptozotocin (30 mg/kg) to induce T 2DM model. After modeling , administration groups were given relevant medicine intragastrically,normal group and model group were given constant volume of normal saline intragastrically ,once a day ,for consecutive 4 weeks. The body weight ,fasting blood glucose and oral glucose tolerance were measured ;serum levels of glycosylated serum protein (GSP),total cholesterol (TC),triacylglycerol(TG),glutathione peroxidase (GSH-Px),superoxide dismutase(SOD),malondialdehyde(MDA),creatine kinase isoenzyme-MB (CK-MB) and troponin Ⅰ (cTn Ⅰ) were determined. The pathomorphological changes of myocardium were observed. The apoptosis index of rat cardiomyocytes was ( detected. The protein expression of B-cell lymphoma 2 (Bcl-2),Bcl-2 related X protein (Bax)and caspase- 3 in rat myocardium were detected by immunohistochemistry and Western blot. RE SULTS:Compared with normal group ,the body weight ,serum levels of GSH-Px and SOD ,protein expression of Bcl- 2 in myocardium were decreased significantly in model group(P<0.01);while fasting blood glucose ,area under blood glucose curve ,serum levels of biochemical indexes (GSP,TC, TG,MDA,CK-MB,cTnⅠ),cardiomyocyte apoptosis index ,protein expression of Bax and caspase- 3 in myocardium were increased significantly (P<0.05 or P<0.01). The arrangement of myocardium was relatively irregular ,and some muscle fibers were broken. Compared with model group ,except for body weight ,serum levels of SOD and MDA ,the protein expression of Bax in myocardium in PF low-dose group , above indexes of PF groups were reversed significantly (P<0.05 or P<0.01). CONCLUSIONS:PF can regulate glycolipid metabolism ,enhance antioxidant ability ,inhibit cardiomyocyte apoptosis and improve myocardial injury in T 2DM model rats ;the mechanism may be associated with increasing the protein expression of Bcl- 2 and down-regulating the protein expression of Bax and caspase- 3 in myocardium.
期刊: 2021年第32卷第23期
作者: 李姗姗,田春雨,张国伟,马雷雷,李继安,刘佳璇,刘颖,李爽,李小龙,沈佳欢
AUTHORS: LI Shanshan,TIAN Chunyu, ZHANG Guowei,MA Leilei,LI Ji ’an,LIU Jiaxuan,LIU Ying,LI Shuang,LI Xiaolong,SHEN Jiahuan
关键字: 芍药苷;2型糖尿病;心肌损伤;细胞凋亡
KEYWORDS: Paeoniflorin;Type 2 diabetes mellitus ;Myocardial injury ;Apoptosis
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