本文選題：高脂　切入點：內(nèi)質(zhì)網(wǎng)應(yīng)激　出處：《重慶醫(yī)科大學(xué)》2010年碩士論文

【摘要】： 目的探討內(nèi)質(zhì)網(wǎng)應(yīng)激在高脂引起的腎臟損傷中的作用及辛伐他汀的干預(yù)作用。 方法30只雄性Wistar大鼠隨機(jī)分為三組:正常對照組(n=10)給予普通飼料喂養(yǎng);高脂組(n=10)給予高脂飼料喂養(yǎng);辛伐他汀組(n=10)在高脂飼料喂養(yǎng)的基礎(chǔ)上給予辛伐他汀10 mg-1·kg-1·d-1灌胃。18周后檢測大鼠24小時尿蛋白及血清膽固醇、甘油三酯水平。光鏡觀察大鼠腎組織病理改變。免疫組化方法檢測大鼠腎臟GRP78、p-JNK蛋白的表達(dá)。TUNEL檢測腎組織細(xì)胞凋亡情況。RT-PCR檢測腎組織GRP78 mRNA、CHOP mRNA的表達(dá)。 結(jié)果18周時,高脂組大鼠:(1)體重與正常對照組比較差異無顯著性(P0.05);(2)24小時尿蛋白、血脂水平均較正常對照組顯著增加,差異有顯著性(P0.01);(3)腎固有細(xì)胞凋亡較對照組明顯增加,差異有顯著性(P0.01);(4)腎組織GRP78及p-JNK蛋白的表達(dá)均較正常對照組顯著增加,差異有顯著性(P0.01);(5)腎組織GRP78及CHOP mRNA的表達(dá)較正常對照組顯著增加,差異有顯著性(P0.01);辛伐他汀組大鼠:(1)體重與正常對照組及高脂組比較差異無顯著性(P0.05);(2)24小時尿蛋白、血脂水平均較正常對照組顯著增加,差異有顯著性(P0.05),但較高脂組顯著降低,差異有顯著性(P0.05);(3)腎固有細(xì)胞凋亡較對照組明顯增加差異有顯著性(P0.05),但較高脂組顯著降低,差異有顯著性(P0.05);(4)腎組織GRP78及p-JNK蛋白的表達(dá)均較正常對照組顯著增加,差異有顯著性(P0.05),但較高脂組顯著降低,差異有顯著性(P0.05);(5)腎組織GRP78 mRNA的表達(dá)較正常對照組顯著增加,差異有顯著性(P0.05),但較高脂組顯著降低,差異有顯著性(P0.05);(6)腎組織CHOP mRNA表達(dá)與正常對照組比較差異無顯著性(P0.05),較高脂組顯著降低,差異有顯著性(P0.05); 相關(guān)性分析:高脂組及辛伐他汀組大鼠腎固有細(xì)胞凋亡指數(shù)與24h尿蛋白定量呈正相關(guān);腎組織GRP78蛋白及mRNA表達(dá)與腎固有細(xì)胞凋亡指數(shù)呈正相關(guān);腎組織p-JNK蛋白表達(dá)與腎固有細(xì)胞凋亡指數(shù)呈正相關(guān);腎組織CHOP mRNA表達(dá)與腎固有細(xì)胞凋亡指數(shù)呈正相關(guān)。 結(jié)論內(nèi)質(zhì)網(wǎng)應(yīng)激參與了高脂引起的腎臟損傷,辛伐他汀可以通過抑制腎臟的內(nèi)質(zhì)網(wǎng)應(yīng)激反應(yīng)而減輕高脂引起的腎臟損傷。
[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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R363.2

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