辛伐他汀对糖尿病大鼠心肌纤维化的保护作用及机制研究

Simvastatin Protects Myocardial Fibrosis in Diabetic Rats by Inhibiting Bcl-2/Bax/Caspase-3 Signaling Pathway

探讨辛伐他汀保护糖尿大鼠心肌纤维化的作用及相关信号通路。将60只SD大鼠依据随机数字的方法分为对照组(BC组)、糖尿病组(DM组)、血管紧张素转换酶抑制剂组(ACEI组)及辛伐他汀组(SIM组)。BC组:正常饲养,不采取任何处理。对照组之外的45只大鼠均构建糖尿病心肌纤维化模型。DM组:造模成功后,正常饲养,不再采取任何干预措施。ACEI组:造模成功后,按照ACEI(卡托普利) 10 mg/kg标准进行灌胃给药。SIM组:造模成功后,按照辛伐他汀10 mg/kg标准进行灌胃给药。检测4组大鼠的血生化及血脂相关指标;实验结束后,处死大鼠,采用RT-PCR及Western-blot检测心肌凋亡相关基因的表达。(1)与BC组比较,DM组大鼠各项血脂指标水平均显著升高(P<0.05)。与DM组比较,SIM组大鼠的血清甘油三酯(TG)、胆固醇(TC)、心脏指数(H/B)、左室重量指数(LVWI)显著下降(P<0.05),但仍然高于BC组(P<0.05),而FBG水平与DM组无明显差异(P>0.05)。(2) BC组大鼠胰岛结构正常,胞质丰富,无炎性细胞浸润。DM组大鼠腺泡扩张,胰岛细胞排列紊乱,核固缩多见。与DM组比较,ACEI组及SIM组的胰腺结构相对清晰完整,腺泡扩张程度减轻,核固缩数量较少。(3)与BC组比较,DM组大鼠心肌细胞中Bcl-2蛋白表达水平显著较低,Bax蛋白、Cleaved-casapase 3蛋白、Casapase 3蛋白表达水平明显较高(P<0.05);与DM组比较,SIM组的Bcl-2蛋白表达水平显著升高(P<0.05),Bax蛋白、Cleaved-casapase 3蛋白、Casapase 3蛋白表达水平明显降低(P<0.05),蛋白表达趋势与RT-PCR一致。辛伐他汀可通过抑制Bcl-2/Bax/caspase-3信号通路活性对糖尿病心肌病大鼠发挥心肌保护作用。

To explore the mechanism of simvastatin protecting cardiomyocytes in diabetic cardiomyopathy rats and its related signaling pathway,60 SD rats were divided into control group(BC group),diabetes group(DM group),angiotensin-converting enzyme inhibitor group(ACEI group) and simvastatin group(SIM group) based on the method of random numbers.BC group:normal breeding without any treatment.In forty-five rats outside the control group were all established diabetic myocardial fibrosis models.DM group:after successful modeling,the animals were raised normally without any intervention.ACEI group:after successful modeling,intragastric administration was performed based on the ACEI(Captopril) 10 mg/kg standard.SIM group:after successful modeling,intragastric administration was performed based on the simvastatin 10 mg/kg standard.The blood biochemical and lipid-related indicators of the four groups of rats were detected.After the experiment,the rats were sacrificed,and the expression of myocardial apoptosis-related genes was detected by RT-PCR and Western-blot.(1) Compared with BC group,the levels of blood lipid in DM group were significantly higher(P<0.05).Compared with DM,TG,TC,H/B and LVWI in SIM group decreased significantly(P<0.05).(2) In BC group,the islets were normal in structure,rich in cytoplasm and without inflammatory cell infiltration.Compared with DM group,the structure of pancreas in ACEI group and SIM group was relatively clear and complete,the degree of acinar expansion was reduced,and the number of nuclear pyknosis was less.(3) Compared with BC group,the expression level of Bcl-2 protein in DM group was significantly lower,Bax protein,cleaved caspase 3 protein and caspase 3 protein were significantly higher(P<0.05);Compared with DM group,the expression level of Bcl-2 protein in SIM group was significantly higher(P<0.05),Bax protein,cleaved caspase 3 protein and caspase 3 protein were significantly lower(P<0.05).The protein expression trend was consistent with RT-PCR.Simvastatin can protect the myocardium of diabetic cardiomyopathy rats by inhibiting the activity of Bcl-2/Bax/caspase-3 signaling pathway.