丝胶对2型糖尿病大鼠肝脏组织中TNF-α和HNF-4α表达的影响

Effects of sericin on TNF-αand HNF-4α expressions in liver tissue of rats with type 2 diabetes mellitus

目的:通过观察丝胶对2型糖尿病大鼠肝脏组织中肿瘤坏死因子α(TNF-α)和肝细胞核因子4α(HNF-4α)表达的影响,探讨丝胶治疗糖尿病的可能机制。方法:36只雄性SD大鼠随机分为正常对照组、糖尿病模型组和丝胶治疗组,每组12只。链脲佐菌素(STZ)连续腹腔注射法制作2型糖尿病大鼠模型。待模型成功建立后,模型组大鼠不做任何处理,丝胶治疗组大鼠给予丝胶(2.4g·kg-1·d-1)灌胃35d。采用免疫组织化学SP法染色、蛋白免疫印迹法和RT-PCR法检测大鼠肝脏组织中TNF-α和HNF-4α的表达。结果:TNF-α蛋白免疫产物为棕黄色和棕褐色颗粒状,位于肝细胞的细胞浆;HNF-4α免疫阳性产物为棕褐色,位于肝细胞的细胞核。与正常对照组比较,糖尿病模型组大鼠肝脏组织中TNF-α、HNF-4α蛋白和mRNA的表达水平明显升高(P<0.01);与糖尿病模型组比较,丝胶治疗组大鼠肝脏TNF-α、HNF-4α蛋白和mRNA的表达水平明显降低(P<0.01)。结论:丝胶可能通过下调肝脏组织中TNF-α和HNF-4α的表达保护糖尿病时肝脏损伤。

Objective To investigate the possible mechanisms of sericin in treating diabetes mellitus by observing the effects of sericin on the expressions of tumor necrosis factor-α（TNF-α）and hepatocyte nuclear factor 4alpha（HNF-4α）in liver tissue of the rats with type 2diabetes mellitus.Methods 36 male SD rats were randomly divided into normal control group,diabetes model group and sericin treatment group（n=12）.The type 2diabetes mellitus rat models were induced by continuously intraperitoneal injection of streptozotocin（STZ）.After successfully establishing the diabetes models,the rats in diabetes model group received any more treatments,and the rats in sericin treatment group were lavaged with sericin（2.4g·kg^-1·d^-1）for 35 d.SP immunohistochemical staining,Western blotting and RT-PCR were used to detect the TNF-αand HNF-4αexpressions in liver tissue of the rats.Results The TNF-αprotein immune positive products were tan and brown granules and located in the cytoplasm of liver cells;the HNF-4αimmune positive products were tan and located in the nucleus of liver cells.Compared with normal control group,the TNF-αand HNF-4αprotein and mRNA expression levels in liver tissue of the rats in diabetes model group were increased obviously（P〈0.01）.Compared with diabetes model group,the TNF-αand HNF-4αprotein and mRNA expression levels in liver tissue of the rats in sericin treatment group were decreased obviously（P〈0.01）.Conclusion Sericin may protect the liver injury in the rats with diabetes mellitus by downregulating the TNF-αand HNF-4αexpressions in liver tissue.