【摘要】：目的：探討高鹽飲食對(duì)Wistar大鼠腎損害的影響及替米沙坦和辣椒素的干預(yù)作用。 方法：Wistar雄性大鼠65只，隨機(jī)分為正常鹽對(duì)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?jī)芍軠y(cè)定尾動(dòng)脈壓一次，喂養(yǎng)24周。實(shí)驗(yàn)結(jié)束后，根據(jù)尾動(dòng)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(jié)構(gòu)，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(shí)大鼠尿液測(cè)定Na+、K+、微量白蛋白、視黃醇結(jié)合蛋白（RBP）、TH糖蛋白（THP）、末次尿總蛋白及肌酐，評(píng)價(jià)腎功能；檢測(cè)腎臟皮質(zhì)Na+-K+-ATP酶、Ca2+-ATP酶活性；免疫組化法檢測(cè)Na+-K+-ATPaseα1、PPARγ、p-NF-κB p65的表達(dá)；運(yùn)用real time RT-PCR法檢測(cè)腎皮質(zhì)Na+-K+-ATPaseα1、PMCA1的mRNA表達(dá)；免疫印跡法檢測(cè)皮質(zhì)Na+-K+-ATPaseα1、皮髓質(zhì)PPARγ、皮髓質(zhì)p-NF-κB p65的蛋白表達(dá)。 結(jié)果：與對(duì)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(jié)果顯示高鹽組腎臟形態(tài)結(jié)構(gòu)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(duì)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(shí)尿總蛋白增高（P0.05）；與對(duì)照組相比，高鹽組24小時(shí)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(shí)尿微量白蛋白高于高鹽正常血壓組（P0.05）；與對(duì)照組相比，高鹽組、替米沙坦組和辣椒素組24h尿視黃醇結(jié)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(wú)改變。高鹽組腎皮質(zhì)Na+-K+-ATP酶活性和Ca2+-ATP酶活性都明顯低于對(duì)照組（P0.05），而Na+-K+-ATPaseα1、PMCA1的mRNA表達(dá)增高。與對(duì)照組相比，高鹽組、替米沙坦組腎臟皮髓質(zhì)PPARγ、p-NF-κB p65表達(dá)明顯增高（P0.05）。 結(jié)論：（1）長(zhǎng)期高鹽飲食可導(dǎo)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(dú)立于血壓直接導(dǎo)致腎功能損害。（3）高鹽飲食致Wistar大鼠腎功能損傷的機(jī)制可能與鈉、鈣泵活性降低及PPARγ、NF-κB p65激活有關(guān)。（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(dá)有關(guān)。（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(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R544.1;R692

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 于海榮;范洪亮;梅愛(ài)敏;任立群;景文麗;張樹(shù)峰;;不同濃度高鹽飼料喂養(yǎng)致高血壓模型的實(shí)驗(yàn)研究[J];山東醫(yī)藥;2012年32期

2 曾昭華,Robert M.K.W.Lee,羅碧輝,GaoYu-jin,何兆初,蘇誠(chéng)堅(jiān);一種新的高鹽致高血壓動(dòng)物模型及其血管重構(gòu)改變[J];中國(guó)臨床藥理學(xué)與治療學(xué);2005年01期

3 劉治全;血壓的鹽敏感性與鹽敏感性高血壓[J];高血壓雜志;2005年03期

4 馬紅;楊香玖;黃延玲;黃群;張巖;陳小敏;沈興平;;血管緊張素Ⅱ受體拮抗劑對(duì)糖尿病腎病患者微量白蛋白尿的作用不受血壓影響[J];中華高血壓雜志;2006年12期

5 牟建軍;楊軍;劉治全;劉衛(wèi)民;任潔;浦曉梅;徐祥麟;;鹽敏感性對(duì)青少年遠(yuǎn)期血壓變化及高血壓發(fā)生的影響[J];中華高血壓雜志;2008年05期

6 胡威;商黔惠;姜黔峰;吳芹;袁萍;;依那普利、厄貝沙坦單用和聯(lián)用對(duì)高血壓大鼠主動(dòng)脈重塑與中膜鈉泵及鈣泵的影響[J];中華高血壓雜志;2010年06期

7 劉文輝,劉治全,候嶸,劉杰;慢性鹽負(fù)荷對(duì)血壓正常鹽敏感性個(gè)體胰島素抗性的影響[J];高血壓雜志;1998年02期

8 趙光勝;高血壓(1)胰島素抵抗與高血壓病[J];中國(guó)循環(huán)雜志;1997年01期

9 商黔惠,王丕榮,李琮輝,馬淑玉,陳劍玲,文雍;多種血管活性物質(zhì)與細(xì)胞膜離子轉(zhuǎn)運(yùn)與高血壓的相互關(guān)系[J];中華心血管病雜志;1998年05期

10 王曉春;商黔惠;祝榮文;吳芹;;長(zhǎng)期高鹽飲食對(duì)Wistar大鼠血壓和腎臟的影響及替米沙坦干預(yù)研究[J];中華高血壓雜志;2013年03期

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