Objective:To detect the mechanism of silent information regulator 1 (Sirt1) in regulating S-adenosylhomocysteine hydrolase (SAHH) in the early occurrence and development of diabetic cardiomyopathy by establishingdiabetes rat model.Methods:The type 2 diabetes rat model was established by high fat diet with injection of streptozocin.The rats were randomly divided into control group,early diabetes mellitus model group (DM group) and the group with treatment of Resveratrol (RES group).RES group received 2.5 mg/(kg · d) resveratrol by gavage for 2 weeks.HE staining was used to observe the morphological changes of myocardial tissue.Cardiac function indexes were examined by echocardiography.High performance liquid chromatography (HPLC) was used to detect homocysteine (Hcy),S-adenosylmethionine (SAM) and S-adenosyl-L-homocysteine (SAH).The alterations of SAHH and Sirt1 in myocardia were determined by western blot.Results:HE staining showed different levels of infiltration by inflammatory cells and even degeneration in myocardial cells of DM group rats.According to the HPLC results,the expression trends of Hcy and SAH is opposite,the expression of Hcy in DM model group increased,while RES group showed reduced expression trend,which showed a significant difference with the DM group.However,the SAM did not have significant change between the groups.Compared with the control group,the expression of SAHH increased in DM group,while in the RES group,the expression declined compared with DM group.Correspondingly,the Sirt1 showed the opposite trends (all P＜0.01).Conclusion:The expression of SAHH,Hcy and other related factors may be important mechanism during the occurrence and development of early diabetic cardiomyopathy,and the regulation of Sirt1 on SAHH may be an important part of the mechanism.%目的:通过建立糖尿病大鼠模型,探讨沉默信息调节因子(Sirt1)对S-腺苷同型半胱氨酸水解酶(SAHH)糖尿病心肌病早期的调节作用及其机制. 方法:采用高脂饮食联合链脲佐菌素建立2型糖尿病大鼠模型,分为对照组、早期糖尿病模型组(DM组)和白藜芦醇处理组(RES组),RES组给予白藜芦醇2.5 mg/(kg·d)灌胃2周处理.HE染色法观察心肌组织病理结构变化,超声心动图检测心功能相关指标,高效液相色谱法检测同型半胱氨酸(Hcy)、S-腺苷甲硫氨酸(SAM)及S-腺苷同型半胱氨酸(SAH),Western blot检测各组心肌组织SAHH、Srit1等蛋白表达变化. 结果:显微镜下DM组大鼠心肌组织可见不同程度炎细胞浸润、甚至变性,而RES组心肌组织可见少量炎性细胞浸润,少量心肌细胞呈长杆状,坏死灶不明显,嗜酸性变较DM组轻.HPLC检测结果显示对照组、DM组和RES组的Hcy分别为(45.37±7.99)、(101.78±16.77)和(86.33±10.09) μmol/L,DM组和RES组较对照组升高,但RES组低于DM组;SAH分别为(50.33±7.34)、(22.92±4.32)和(33.45±7.88) μmol/L,DM组和RES组较对照组降低,但RES组高于DM组;SAM分别为(66.34±9.99)、(69.56±9.01)和(70.89±11.33) μmol/L,各组间无显著差异;SAHH分别为(44.11±5.17)、(92.33±17.56)和(19.73±4.07) μmol/L,DM组较对照组升高,RES组较对照组降低;Srit1分别为(80.12±10.09)、(29.11±3.91)和(107.32±13.24) μmol/L,DM组较对照组降低,RES组较对照组升高. 结论:SAHH及下游Hcy等的表达可能是早期糖尿病心肌病发生发展的重要作用机制,而Sirt1对SAHH的表达调控作用可能起重要作用.
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