糖脂清对糖尿病大鼠海马内质网应激相关因子GRP78、CHOP、Caspase-12表达的影响

Effects Tangzhiqing on the Expression of Endoplasmic Reticulum Stress Related Factors GRP78,CHOP and Caspase-12 in the Hippocampus of Diabetic Rats

目的通过观察糖脂清对糖尿病大鼠海马组织的内质网应激相关因子GPR78、CHOP、Caspase-12的影响,探讨其在改善糖尿病大鼠认知功能的作用机制。方法采用高糖高脂饲料联合小剂量链脲佐菌素腹腔注射复制2型糖尿病大鼠模型,并给予糖脂清高、中、低剂量组干预8周后,采用ELISA法检测血清空腹葡萄糖(FPG)、空腹胰岛素(FINS),计算稳态模型的胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI);qPCR和Western blot法检测海马组织内质网应激相关因子GPR78、CHOP、Caspase-12的mRNA及蛋白表达水平。结果糖脂清各剂量组均能够显著降低FPG及HOMA-IR(P<0.01),除低剂量组外,糖脂清均可显著提高ISI(P<0.01),3组FINS水平无显著性差异(P>0.05)。与模型组比较,糖脂清低、中、高3个剂量组GRP78mRNA和蛋白相对表达均显著增加,CHOP、Caspase-12mRNA表达均减少(P<0.01),中、高剂量组CHOP、Caspase-12蛋白表达显著减少(P<0.01)。结论糖脂清能够控制血糖,改善胰岛素抵抗,增加胰岛素敏感性,同时能够调节海马内质网应激相关因子GRP78、CHOP、Caspase-12mRNA和蛋白的表达。

OBJECTIVE To observe the effect of Tangzhiqing on the endoplasmic reticulum stress related factors GPR78,CHOP and Caspase-12 in hippocampus of diabetic rats,and to explore its mechanism of improving cognitive function in diabetic rats.METHODS The model of type 2 diabetes mellitus rats was established by intraperitoneal injection of low-dose of streptozotocin combined with high-sugar and high-fat diet,After 8 weeks of intervention with high,medium and low-dose of Tangzhiqing,serum fasting glucose(FPG)and fasting insulin(FINS)were detected by ELISA,the index of insulin resistance(HOMA-IR)and insulin sensitivity index(ISI)were calculated;the expression levels of endoplasmic reticulum stress related genes GPR78,CHOP and Caspase-12 mRNA and protein in hippocampus were detected by qPCR and Western blot assay.RESULTS Different dosages of Tangzhiqing significantly decreased FPG and HOMA-IR(P<0.01);except the low dose group,Tangzhiqing significantly improved ISI(P<0.01);no significant difference existed in FPG level among the 3 groups(P>0.05).Compared to the model group,the relative expression of GRP78 mRNA and protein in the 3 groups of Tangzhiqing increased significantly,and the expression of CHOP and Caspase-12 mRNA in these 3 groups decreased(P<0.01).CHOP and Caspase-12 in middle and high dose group decreased significantly(P<0.01).CONCLUSION Tangzhiqing can control blood sugar,improve insulin resistance,increase insulin sensitivity and regulate the expression of GRP78,CHOP,Caspase-12 in hippocampus.