丝胶蛋白对2型糖尿病大鼠肾脏氧化应激损伤和PI3K/Akt信号通路的影响

Effects of sericin on oxidative stress injury and PI3K/Akt signaling pathway in kidney of type 2 diabetic rats

目的探讨丝胶蛋白(彩色蚕茧水提物)对2型糖尿病大鼠肾脏氧化应激损伤和磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(Akt)信号通路的影响。方法48只SD大鼠随机均分为四组各12只,正常对照组、2型糖尿病模型组、丝胶低剂量灌胃组、丝胶高剂量灌胃组。采用高脂高糖饲料饲养+链脲佐菌素(35 mg/kg,2次)腹腔注射的方法建模,成模标准是空腹血糖≥11.1 mmol/L。待建模成功后,丝胶低〔1.8 g/(kg·d)〕、高〔2.4 g(kg·d)〕剂量组大鼠分别给予不同剂量丝胶连续灌胃35 d。分别检测各组大鼠血糖,血尿素氮和肌酐水平;分别检测各组大鼠肾脏超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、总一氧化氮合酶(tNOS)、过氧化氢(H2O2)的水平;采用Real Time Q-PCR法分别检测各组大鼠肾脏PI3K、Akt mRNA的表达。结果丝胶低、高剂量组大鼠肾脏SOD、CAT水平及肾脏PI3K、Akt mRNA的表达明显高于模型组(P<0.01,P<0.05);血糖,血尿素氮和肌酐水平及肾脏tNOS、H2O2水平明显低于对照组(P<0.01)。并且,丝胶高剂量组大鼠肾脏CAT水平、PI3K mRNA的表达明显高于低剂量组,血尿素氮和肾脏H2O2水平明显低于低剂量组(P<0.01)。结论丝胶蛋白对2型糖尿病时肾脏损伤具有保护作用,其机制可能与丝胶蛋白能抑制肾脏氧化应激损伤和激活PI3K/Akt信号通路有关。

Objective To investigate the effects of sericin(water extract of coloured silkworm cocoon)on oxidative stress injury and PI3K/Akt signaling pathway in kidney of type 2 diabetic rats.Methods 48 SD rats were randomly divided into 4 groups on average(n=12):normal control,type 2 diabetic model,low and high dose sericin intragastric adminstration groups.The model was established by feeding with high-fat and high-sugar diet combined intraperitoneal injection of streptozotocin(35 mg/kg,twice),and the standard for establishing the model successfully was fasting blood glucose≥11.1 mmol/L.The blood glucose,blood urea nitrogen and blood creatinine of rats in each group were measured.The level of superoxide dismutase(SOD),catalase(CAT),total nitric oxide synthase(tNOS),hydrogen peroxide(H 2O 2)in kidney of rats in each group were detected.Real time Q-PCR was used to detect PI3K,Akt mRNA expression in kidney of rats in each group.Results The level of SOD and CAT,as well as PI3K and Akt mRNA expression in kidney of rats in two sericin intragastric adminstration groups were remarkably higher than those of model group(P<0.01,P<0.05).While the blood glucose,blood urea nitrogen and blood creatinine,the level of tNOS,H 2O 2 in kidney of rats in two sericin intragastric adminstration groups were remarkably lower than those of model group(P<0.01).Also,the level of CAT and PI3K mRNA expression in kidney of rats in high dose sericin intragastric adminstration group were obviously higher than those of low dose group,while the blood urea nitrogen and H 2O 2 levels in kidney were obviously lower(P<0.01).Conclusions Sericin has protective effects on kidney damage during type 2 diabetes mellitus.The mechanisms might be related to sericin who could inhibit oxidative stress injury and activate PI3K/Akt signaling pathway of kidney.