丝胶对糖尿病大鼠肾脏ERK信号通路的影响

Effects of Sericin on ERK Signaling Pathway of Diabetic Rats′ Kidney

目的探讨彩色蚕茧提取物——丝胶对2型糖尿病大鼠肾脏细胞外信号调节激酶(ERK)信号通路的作用。方法雄性SD大鼠48只,随机均分为4组:正常对照组、糖尿病模型组、丝胶治疗组和二甲双胍组。糖尿病模型组、丝胶治疗组和二甲双胍组大鼠均建立链脲佐菌素(2%,25 mg.kg-1,3 d)致2型糖尿病大鼠模型;模型成功建立后,丝胶治疗组和二甲双胍组大鼠分别给予丝胶(2.4 g.kg-1.d-1)和二甲双胍(55.33 mg.kg-1.d-1)灌胃治疗35 d。分别采用Western blot和RT-PCR法检测ERK信号通路相关因子ERK、丝裂原活化蛋白激酶的激酶(MEK)和原癌基因c-fos蛋白和mRNA的表达。结果糖尿病模型组大鼠肾脏ERK、MEK、c-fos的表达较正常对照组大鼠增高,差异具有统计学意义(P<0.01);丝胶治疗组、二甲双胍组ERK、MEK、c-fos的表达较糖尿病模型组大鼠降低,差异具有统计学意义(P<0.05)。结论肾脏ERK信号通路的激活可能参与了糖尿病肾脏损害的发生发展。丝胶可通过下调ERK及其上游MEK、下游c-fos的表达,抑制糖尿病大鼠肾脏ERK信号通路的激活,发挥对糖尿病大鼠肾脏损伤的保护作用。

Objective To investigate the effects of sericin on extracellular signal regulated kinase （ERK） signaling pathway of diabetic rats＇ kidney. Methods A total of 48 male SD rats were randomly divided into 4 groups （n =12）：normal control group, diabetes model group, sericin treatment group and metformin group. The type 2 diabetes rats model was established by peritoneal injection of small dose streptozotocin （2%, 25 mg kg-1, 3 d）. After the diabetes rat model was successfully established, the rats in sericin treatment group were ad- ministrated with sericin （2.4 g kg-1 d-1） for 35 days,and the rats in metformin group were given mefformin （55.33 mg kg-1 d-1） for 35 days. Expressions of ERK, mitogen-activated protein kirmse kinase （MEK） and proto-oncogene c-fos in kidney were detected by Western blot and RT-PCR. Results Both protein and mRNA expressions of ERK, MEK, and c-fos in kidney of diabetes rats were significantly higher than control ones （P 〈 0.01 ）. With sericin and mefformin treatment, the ERK, MEK, c-fos protein and mRNA expressions were significantly reduced （P 〈 0.05 ）. Conclusion Activating of ERK signaling pathway of diabetes rats may involve the development of kidney injury dur- ing diabetes. Sericin can inhibit activation of ERK signal pathway by down-regulating expression of MEK, ERK and c-fos in diabetes rats; therefore, sericin has protective effects on kidney injury of diabetes rats.