【摘要】：目的：探討高鹽飲食對Wistar大鼠腎損害的影響及替米沙坦和辣椒素的干預作用。 方法：Wistar雄性大鼠65只，隨機分為正常鹽對照組（NSD組，0.5%NaCl的顆粒飼料喂養(yǎng)），高鹽組（HSD組，4%NaCl的顆粒飼料喂養(yǎng)），高鹽+替米沙坦組（HSD+ARB組，4%NaCl的顆粒飼料喂養(yǎng)+替米沙坦），高鹽+辣椒素組（HSD+CAP組，，4%NaCl的顆粒飼料+辣椒素），每兩周測定尾動脈壓一次，喂養(yǎng)24周。實驗結束后，根據(jù)尾動脈壓再將高鹽組分為高鹽高血壓組（HSD-H組）、高鹽正常血壓組（HSD-N組）。各組大鼠取雙腎， HE染色觀察腎臟的形態(tài)結構，Masson染色觀察腎臟及血管壁的纖維化程度；階段性收集24小時大鼠尿液測定Na+、K+、微量白蛋白、視黃醇結合蛋白（RBP）、TH糖蛋白（THP）、末次尿總蛋白及肌酐，評價腎功能；檢測腎臟皮質Na+-K+-ATP酶、Ca2+-ATP酶活性；免疫組化法檢測Na+-K+-ATPaseα1、PPARγ、p-NF-κB p65的表達；運用real time RT-PCR法檢測腎皮質Na+-K+-ATPaseα1、PMCA1的mRNA表達；免疫印跡法檢測皮質Na+-K+-ATPaseα1、皮髓質PPARγ、皮髓質p-NF-κB p65的蛋白表達。 結果：與對照組相比，高鹽高血壓組較其他各組血壓升高（P0.05）。HE和Masson結果顯示高鹽組腎臟形態(tài)結構有不同程度的損害，替米沙坦和辣椒素可明顯改善其腎損害。與對照組相比，高鹽組、替米沙坦組和辣椒素組24h尿鈉鉀比值、24小時尿總蛋白增高（P0.05）；與對照組相比，高鹽組24小時尿微量白蛋白顯著增高（P0.05），替米沙坦組和辣椒素組低于高鹽組（P0.05），高鹽高血壓組24小時尿微量白蛋白高于高鹽正常血壓組（P0.05）；與對照組相比，高鹽組、替米沙坦組和辣椒素組24h尿視黃醇結合蛋白和TH糖蛋白升高（P0.05），高鹽組和替米沙坦組肌酐清除率降低（P0.05），而辣椒素組肌酐清除率無改變。高鹽組腎皮質Na+-K+-ATP酶活性和Ca2+-ATP酶活性都明顯低于對照組（P0.05），而Na+-K+-ATPaseα1、PMCA1的mRNA表達增高。與對照組相比，高鹽組、替米沙坦組腎臟皮髓質PPARγ、p-NF-κB p65表達明顯增高（P0.05）。 結論：（1）長期高鹽飲食可導致部分Wistar大鼠血壓升高，部分大鼠血壓不升高。（2）高鹽飲食可獨立于血壓直接導致腎功能損害。（3）高鹽飲食致Wistar大鼠腎功能損傷的機制可能與鈉、鈣泵活性降低及PPARγ、NF-κB p65激活有關。（4）替米沙坦具有降壓和改善腎功能的作用，可能與激活PPARγ及抑制NF-κB p65蛋白表達有關。（5）辣椒素具有降壓和改善腎損害的作用。
[Abstract]:Aim: to investigate the effects of high salt diet on renal damage in Wistar rats and the effects of telmisartan and capsaicin. Methods Sixty-five male Wistar rats were used. They were randomly divided into normal salt control group (NSD group), high salt group (HSD group), high salt telmisartan group (HSD ARB group), high salt capsaicin group (HSD CAP group), high salt telmisartan group (HSD ARB group) and high salt capsaicin group (HSD CAP group). The caudal arterial pressure was measured every two weeks. Feeding for 24 weeks. After the experiment, according to the caudal arterial pressure, the high salt components were divided into high salt hypertension group (HSD-H group) and hypersalt normal blood pressure group (HSD-N group). The two kidneys were taken from each group, the morphology and structure of kidney were observed by HE staining and the degree of fibrosis of kidney and vascular wall was observed by Masson staining. Retinol binding protein (RBP) TH glycoprotein (THP), total protein and creatinine in the last urine were used to evaluate renal function, the activity of Na K ATPase Ca 2 + ATPase in renal cortex and the expression of Na K ATPase 偽 1 PPAR 緯 -nf 魏 B p65 in renal cortex were detected by immunohistochemistry. Real time RT-PCR was used to detect the expression of Na -K -ATPase 偽 1 and protein expression of p-NF- 魏 B p65 in cortical Na K ATPase 偽 1, skin medulla PPAR 緯 and medulla p65 in renal cortex. Results: compared with the control group, the blood pressure in the high salt hypertension group was higher than that in the other groups (P0.05). The results of HE and Masson showed that the renal morphology in the high salt group was damaged to some extent, and telmisartan and capsaicin could significantly improve the renal damage. Compared with control group, the ratio of 24 hours urinary sodium and potassium in high salt group, telmisartan group and capsaicin group was higher than that in control group (P0.05). In high salt group, 24 hours urinary microalbumin was significantly increased (P0.05), telmisartan group and capsaicin group were lower than those in high salt group (P0.05), 24 hour urinary microalbumin in high salt hypertension group was higher than that in high salt normal blood pressure group (P0.05), compared with control group, high salt group, In telmisartan group and capsaicin group, 24 hours urinary retinol binding protein and th glycoprotein were increased (P0.05), creatinine clearance was decreased in high salt group and telmisartan group (P0.05), but creatinine clearance rate was not changed in capsaicin group. The Na K ATPase activity and Ca 2 ATPase activity in the renal cortex of high salt group were significantly lower than those in the control group (P 0.05), while the mRNA expression of Na K ATPase 偽 1 and PMCA 1 was increased. Compared with the control group, the expression of PPAR 緯 -NF- 魏 B p65 in renal medulla was significantly increased in high-salt group and telmisartan group (P0.05). Conclusion: (1) Long-term high salt diet can increase blood pressure of some Wistar rats, while some rats' blood pressure does not. (2) High salt diet can directly lead to renal function damage independently of blood pressure. (3) the mechanism of renal function damage in Wistar rats induced by high salt diet may be related to sodium. The decrease of calcium pump activity and the activation of PPAR 緯 -NF- 魏 B p65. (4) telmisartan can reduce blood pressure and improve renal function, which may be related to activation of PPAR 緯 and inhibition of NF- 魏 B p65 protein expression. (5) capsaicin can reduce blood pressure and ameliorate renal damage.
【學位授予單位】：遵義醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R544.1;R692

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