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Received:November 18, 2019 Published Online:July 20, 2020
Received:November 18, 2019 Published Online:July 20, 2020
中文摘要: 目的 探讨瑞舒伐他对汀糖尿病心肌病大鼠心肌细胞的保护机制及其相关信号通路。
方法 将50只SD大鼠随机分为对照组(n=10)正常饲养不给任何处理,其他40只采用腹腔注射STZ构建糖尿病心肌病模型成功后再随机分为四组(n=10):模型组(正常饲养,不给药)、白蒺藜组(白蒺藜10 mg/kg灌胃)、瑞舒伐他汀组(瑞舒伐他汀10 mg/kg灌胃)、联合组(予同剂量白蒺藜及瑞舒伐他汀灌胃),均连续给药8周。检测各组大鼠的血糖血脂相关指标及血清丙二醛(MDA)、超氧化物歧化酶(SOD)和肌酸激酶同工酶(CK-MB)水平;实验结束后,处死大鼠,采用RT-qPCR及Western blot检测模型组和三个给药组大鼠B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、胱天蛋白酶（casapase)3、裂解型（Cleaved）casapase3在基因及蛋白层面的表达水平。
结果 (1)与模型组相比,给药三组大鼠血糖、糖化血红蛋白、MDA、CK-MB水平及血脂指标明显下降(P均<0.05),SOD及HDL-C水平明显升高(P均<0.05),联合治疗组改变更显著。(2)Masson染色结果显示,模型组大鼠心肌纤维排列紊乱,增大增粗,部分纤维断裂溶解；与模型组相比,给药三组大鼠心肌纤维损伤明显减轻,纤维断裂数量减少,联合组纤维损伤减轻更明显。(3)RT-qPCR检测发现,与对照组比较,模型组大鼠心肌细胞中Bcl-2 mRNA表达水平显著降低,Bax、Cleaved casapase3和casapase3的mRNA表达水平明显升高(P均<0.05);与模型组比较,给药三组的Bcl-2 mRNA表达水平显著升高(P<0.05),Bax、Cleaved casapase3和casapase3的mRNA表达水平明显降低(P均<0.05)。Western blot检测显示相关蛋白变化趋势与RT-qPCR结果一致。
结论 瑞舒伐他汀可通过抑制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。
Abstract:Objective To explore the protective mechanism and related signal pathway of rosuvastate on cardiomyocytes of diabetic cardiomyopathy rats.
Methods Out of 50 SD rats,10 were served as control group,40 diabetic cardiomyopathy models were randomly subdivided into model group(no administration),the other three groups of intragastric administration:tibulus terrestris group,rosuvastatin group and combined group (Tribulus terrestris and rosuvastatin) after established by intraperitoneal injection of STZ(n=10,each ).Intragastric administration continued for 8 weeks.The levels of related indexes of blood glucose and lipid,serum MDA,SOD and CK-MB were determined,and the expression levels of Bcl-2,Bax,caspase-3 and Cleaved caspase-3 were detected by RT-qPCR and Western blot after the rats were killed at the end of the experiment.
Results Compared with the model group,the levels of blood glucose,glycosylated hemoglobin(GHb),MDA,CK-MB and blood lipid related indexes significantly decreased (all P<0.05),and the levels of SOD and HDL-C significantly increased in three groups of administration(all P<0.05),and the most-significant change was in combined group.Masson staining showed that the injury of myocardial fibers and the number of fiber breaks decreased obviously in three proups of administration,especially in combined group compared with model group.RT-qPCR assays showed that compared with control group,the expression level of Bcl-2 mRNA significantly decreased,and the mRNA expression levels of Bax,Cleaved caspase 3 and caspase 3 significantly increased in model group (all P<0.05);compared with model group,the expression level of Bcl-2 mRNA significantly increased,and the mRNA expression levels of Bax,Cleaved caspase 3 and caspase 3 significantly decreased in three groups of administration(all P<0.05).The change trend of related proteins was consistent between Western blot analysis and RT-qPCR assays.
Conclusion Rosuvastatin can protect the myocardium of diabetic cardiomyopathy rats by inhibiting the activity of Bcl-2/Bax/caspase-3 signaling pathway.
文章编号： 中图分类号： 文献标志码：A
基金项目:全军保健专项科研课题(15BJZ07;14BJZ27)
| Author Name | Affiliation |
| SU Li,ZHONG Ping,HAO Ying-qun,GUO Jia,LI Song,GAO Yan | Department of Cadre Ward,the 960th Hospital of PLA,Jinan,Shandong 250031,China |
| Author Name | Affiliation |
| SU Li,ZHONG Ping,HAO Ying-qun,GUO Jia,LI Song,GAO Yan | Department of Cadre Ward,the 960th Hospital of PLA,Jinan,Shandong 250031,China |
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