本文選題：慢性CsA腎毒性 + 水通道蛋白　； 參考：《延邊大學(xué)》2014年碩士論文

【摘要】：目的：探討水通道蛋白(Aquaporin,AQP)在大鼠慢性環(huán)孢素A腎毒性腎中的表達(dá)。 方法：雄性Sprague-Dawley大鼠喂飼低鹽飼料(0.05%鈉鹽)1周后,隨機(jī)分為兩組：1)對(duì)照組(n=8)：皮下注射橄欖油(1mL.kg-1.d-1)；2)CsA腎毒性組(n=8)：皮下注射CsA(15mg.kg-1.d-1);監(jiān)測(cè)兩組大鼠的體重變化、水?dāng)z入量、尿量、腎功能(血尿素氮、血肌酐、內(nèi)生肌酐清除率)；三色染色(Masson染色)觀察腎小管間質(zhì)纖維化；TUNEL檢測(cè)法和電子顯微鏡觀察細(xì)胞凋亡情況；利用免疫組織化學(xué)染色和免疫印跡法分別觀察腎內(nèi)AQP-1、AQP-2、AQP-3在腎臟皮質(zhì)、髓質(zhì)中的表達(dá)。 結(jié)果：與對(duì)照組相比,CsA腎毒性組大鼠表現(xiàn)為每日水?dāng)z入量(24.0±6.0mL vs.15.0±4mL,P0.01).尿量(26±7mL vs.14±6mL,P0.01).血尿素氮(36±7mg/dL vs.15±4mg/dL,P0.01).血肌酐(1.1±0.2mg/dL vs.0.8±0.1mg/dL,P0.01)明顯增加,而體重(328±8g vs.340±5g,P0.01)和內(nèi)生肌酐清除率(0.24±0.04mL/min/100g vs.O.35±0.03mL/min/100g,P0.01)減少；免疫組化法示正常腎組織的近曲小管、髓袢升支細(xì)段、直管降支均有AQP-1的表達(dá),尤其沿皮質(zhì)的刷狀緣高表達(dá),而AQP-1在CsA腎毒性組大鼠內(nèi)髓質(zhì)、外髓質(zhì)中的表達(dá)明顯減少[皮質(zhì)：(48±6%vs.100±5%P0.01)；髓質(zhì)：(44±2%vs.54±3%)AQP-2在正常腎組織的集合管細(xì)胞高表達(dá),而AQP-2在CsA毒性組大鼠腎組織皮質(zhì)的表達(dá)無(wú)變化,在髓質(zhì)的表達(dá)顯著減少(40±2%vs.102±4%,P0.01)；AQP-3豐富表達(dá)于腎臟集合管細(xì)胞基底區(qū),在CsA毒性組AQP-3皮質(zhì)、髓質(zhì)表達(dá)上均明顯減少[皮質(zhì)：(40±2%vs.100±5%)；髓質(zhì)：(38±2%vs.100±5%)]。這些水通道蛋白表達(dá)的變化與腎小管上皮細(xì)胞凋亡數(shù)呈負(fù)向相關(guān)(AQP-1:r=-0.789,P=0.001；AQP-2:r=-0.698,P=0.003; AQP-3:r=-0.515.P=0.041). 結(jié)論：在慢性環(huán)孢A腎毒性中,水通道蛋白1、2、3在皮質(zhì)、髓質(zhì)中的表達(dá)明顯減少,這種現(xiàn)象可能與CsA腎毒性大鼠尿濃縮功能障礙有關(guān)。細(xì)胞凋亡是水通道蛋白表達(dá)減少的分子機(jī)制。
[Abstract]:Aim: to investigate the expression of aquaporin in chronic cyclosporine A nephrotoxic kidney in rats. Methods: male Sprague-Dawley rats were fed with 0.05% sodium salt diet for 1 week, and were randomly divided into two groups: control group (n = 1): subcutaneous injection of olive oil 1 mL 路kg -1 路d -1 and CsA 15 mg 路kg -1 路d -1 路d -1. The body weight, water intake, urine volume of the two groups were monitored. Renal function (blood urea nitrogen, serum creatinine, endogenetic creatinine clearance rate) and renal tubulointerstitial fibrosis (tubulointerstitial fibrosis) were observed by Tunel and electron microscopy. Immunohistochemical staining and Western blotting were used to observe the expression of AQP-1 and AQP-2AQP-3 in renal cortex and medulla respectively. Results: compared with the control group, the rats in CSA nephrotoxicity group showed a daily water intake of 24.0 鹵6.0 mL vs.15.0 鹵4mL P0.01a. Urine volume was 26 鹵7 mL vs.14 鹵6 mL P0.01g. Blood urea nitrogen 36 鹵7 mg / dL vs.15 鹵4 mg / dL P0.01g. Serum creatinine was significantly increased by 1.1 鹵0.2 mg / dL vs.0.8 鹵0.1 mg / dL P0.01), while the body weight was 328 鹵8 g vs.340 鹵5g P0.01) and the creatinine clearance rate was 0.24 鹵0.04mL / min / 100g vs.O.35 鹵0.03mL / P / 100g P0.01.The immunohistochemical method showed that AQP-1 was expressed in the proximal convoluted tubules, the ascending branches of the loop pulposus, and the descending branches of the straight canal, especially along the brush-shaped edge of the cortical cortex. The expression of AQP-1 in the medulla and outer medulla of CSA nephrotoxic rats was significantly decreased [cortical fraction 48 鹵6%vs.100 鹵5P0.01U; medullary: 44 鹵2%vs.54 鹵3p; AQP-2 was overexpressed in the collecting duct cells of normal renal tissue, but AQP-2 expression did not change in CSA toxic group. The expression of AQP-3 was significantly decreased in the medulla (40 鹵2%vs.102 鹵4) and in the basal area of the renal collecting duct cells. In the CSA toxic group, the expression of AQP-3 was significantly decreased [cortex: 40 鹵2%vs.100 鹵5; medulla: 38 鹵2%vs.100 鹵5]. These changes in aquaporin expression were negatively correlated with the number of apoptosis in renal tubular epithelial cells. Conclusion: in chronic cyclosporine A nephrotoxicity, the expression of aquaporin 1, 2 and 3 in cortex and medulla is significantly decreased, which may be related to urinary concentration dysfunction in CSA nephrotoxic rats. Apoptosis is the molecular mechanism of decreased expression of aquaporin.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R692

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