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
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摘要: 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GRP78 mRNA和蛋白相对表达均显著增加,CHOP、Caspase-12 mRNA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-12 mRNA和蛋白的表达。Abstract: 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.
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Key words:
- Tangzhiqing /
- type 2 diabete /
- endoplasmic reticulum stress /
- GRP78 /
- CHOP /
- Caspase-12
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