内质网应激在高脂引起的肾脏损伤中的作及辛伐他汀的干预作用

发布时间：2018-04-09 05:37

本文选题：高脂　切入点：内质网应激　出处：《重庆医科大学》2010年硕士论文

【摘要】： 目的探讨内质网应激在高脂引起的肾脏损伤中的作用及辛伐他汀的干预作用。方法30只雄性Wistar大鼠随机分为三组:正常对照组(n=10)给予普通饲料喂养;高脂组(n=10)给予高脂饲料喂养;辛伐他汀组(n=10)在高脂饲料喂养的基础上给予辛伐他汀10 mg-1·kg-1·d-1灌胃。18周后检测大鼠24小时尿蛋白及血清胆固醇、甘油三酯水平。光镜观察大鼠肾组织病理改变。免疫组化方法检测大鼠肾脏GRP78、p-JNK蛋白的表达。TUNEL检测肾组织细胞凋亡情况。RT-PCR检测肾组织GRP78 mRNA、CHOP mRNA的表达。结果18周时,高脂组大鼠:(1)体重与正常对照组比较差异无显著性(P0.05);(2)24小时尿蛋白、血脂水平均较正常对照组显著增加,差异有显著性(P0.01);(3)肾固有细胞凋亡较对照组明显增加,差异有显著性(P0.01);(4)肾组织GRP78及p-JNK蛋白的表达均较正常对照组显著增加,差异有显著性(P0.01);(5)肾组织GRP78及CHOP mRNA的表达较正常对照组显著增加,差异有显著性(P0.01);辛伐他汀组大鼠:(1)体重与正常对照组及高脂组比较差异无显著性(P0.05);(2)24小时尿蛋白、血脂水平均较正常对照组显著增加,差异有显著性(P0.05),但较高脂组显著降低,差异有显著性(P0.05);(3)肾固有细胞凋亡较对照组明显增加差异有显著性(P0.05),但较高脂组显著降低,差异有显著性(P0.05);(4)肾组织GRP78及p-JNK蛋白的表达均较正常对照组显著增加,差异有显著性(P0.05),但较高脂组显著降低,差异有显著性(P0.05);(5)肾组织GRP78 mRNA的表达较正常对照组显著增加,差异有显著性(P0.05),但较高脂组显著降低,差异有显著性(P0.05);(6)肾组织CHOP mRNA表达与正常对照组比较差异无显著性(P0.05),较高脂组显著降低,差异有显著性(P0.05); 相关性分析:高脂组及辛伐他汀组大鼠肾固有细胞凋亡指数与24h尿蛋白定量呈正相关;肾组织GRP78蛋白及mRNA表达与肾固有细胞凋亡指数呈正相关;肾组织p-JNK蛋白表达与肾固有细胞凋亡指数呈正相关;肾组织CHOP mRNA表达与肾固有细胞凋亡指数呈正相关。结论内质网应激参与了高脂引起的肾脏损伤,辛伐他汀可以通过抑制肾脏的内质网应激反应而减轻高脂引起的肾脏损伤。
[Abstract]:Objective to investigate the role of endoplasmic reticulum stress in hyperlipidemic renal injury and the intervention of simvastatin.Methods Thirty male Wistar rats were randomly divided into three groups: normal control group (n = 10) and high fat group (n = 10).On the basis of high fat diet, simvastatin 10 mg-1 kg-1 d-1 was given to rats. After 18 weeks, urine protein, serum cholesterol and triglyceride levels were measured.The pathological changes of renal tissue were observed under light microscope.Immunohistochemical method was used to detect the expression of GRP78 p-JNK protein. Tunel was used to detect the apoptosis of renal tissue. RT-PCR was used to detect the expression of GRP78 mRNA-chop mRNA in renal tissue.The expression of GRP78 and p-JNK protein in renal tissue was significantly higher than that in normal control group, and the expression of GRP78 and CHOP mRNA in renal tissue was significantly higher than that in normal control group.There was no significant difference in body weight between simvastatin group and normal control group and hyperlipidemia group in 24 hours urine protein, and the level of blood lipid in simvastatin group was significantly higher than that in normal control group (P 0.05), but significantly decreased in high fat group.The expression of GRP78 and p-JNK protein in renal tissue was significantly higher than that in control group, but it was significantly lower in high fat group than that in control group, and the expression of GRP78 and p-JNK protein in renal tissue were significantly higher than that in normal control group (P < 0.05), but the expression of GRP78 and p-JNK in renal tissue were significantly higher than that in normal control group (P < 0.05), and the expression of GRP78 and p-JNK in renal tissue were significantly higher than those in normal control group (P < 0.05).The expression of GRP78 mRNA in the renal tissue was significantly higher than that in the normal control group (P 0.05), but the expression of GRP78 mRNA in the high fat group was significantly lower than that in the control group (P 0.05), but it was significantly lower in the high fat group than that in the control group (P < 0.05), but the expression of GRP78 mRNA in the renal tissue was significantly higher than that in the normal control group (P 0.05).The expression of CHOP mRNA in renal tissue was not significantly different from that in normal control group (P 0.05), but decreased significantly in high fat group (P 0.05).Correlation analysis showed that apoptosis index of renal intrinsic cells was positively correlated with 24 hours urine protein in hyperlipidemia group and simvastatin group, and the expression of GRP78 protein and mRNA in renal tissue was positively correlated with renal inherent cell apoptosis index.The expression of p-JNK protein was positively correlated with the apoptosis index of renal intrinsic cells, and the expression of CHOP mRNA was positively correlated with the apoptosis index of renal inherent cells.Conclusion endoplasmic reticulum stress is involved in renal injury induced by hyperlipidemia and simvastatin can attenuate renal damage induced by hyperlipidemia by inhibiting the endoplasmic reticulum stress.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R363.2

【参考文献】