【摘要】：目的：探討1)環(huán)孢素A (Cyclosporine A, CsA)腎毒性是否可引起模型貧血；2)在慢性CsA腎毒性腎中促紅細(xì)胞生成素(Erythropoietin, EPO)及促紅細(xì)胞生成素受體(EPOR)的表達(dá)情況。 方法：健康Sprague-Dawley大鼠分別給予皮下注射CsA (15mg. kg-1. d-1)和橄欖油(1mL. kg-1, d-1)4周后,建立慢性CsA腎毒性組和對照組。處死前檢測各組大鼠的尿素氮(BUN)、血肌酐(SCr)、血色素(Hb)、紅細(xì)胞壓積(Hct); Masson染色法確定腎小管間質(zhì)纖維化程度；免疫組織化學(xué)染色和免疫印跡法分別觀察腎內(nèi)EPO及EPOR的表達(dá)；TUNEL染色和電子顯微鏡檢測細(xì)胞凋亡。 結(jié)果：與對照組相比,腎毒性組體重下降、腎功能低下、Hb和Hct的下降,伴有貧血發(fā)生；腎毒性組腎小管間質(zhì)帶狀纖維化、細(xì)胞凋亡增加(K0.01); EPO在腎毒性組中的表達(dá)明顯減少,而EPOR的表達(dá)卻明顯加強。直線相關(guān)分析表明,EPO蛋白表達(dá)與TIF和TUNEL陽性細(xì)胞數(shù)呈負(fù)向相關(guān)。 結(jié)論：CsA所致的慢性腎毒性使得腎組織內(nèi)EPO蛋白表達(dá)減少,從而導(dǎo)致造血功能下降,進(jìn)而產(chǎn)生貧血。EPO蛋白表達(dá)減少可能與CsA腎毒性所致腎小管上皮細(xì)胞凋亡有相關(guān)性。
[Abstract]:Objective: to investigate whether cyclosporine A (Cyclosporine A, CsA) nephrotoxicity can induce model anemia, and to investigate the expression of erythropoietin (Erythropoietin, EPO) and erythropoietin receptor (EPOR) in chronic renal CsA nephrotoxicity. Methods: healthy Sprague-Dawley rats were subcutaneously injected with CsA (15 mg 路kg-1. d-1) and olive oil (1 mL 路kg-1, d-1) for 4 weeks, then chronic CsA nephrotoxicity group and control group were established. The renal tubulointerstitial fibrosis degree was determined by (Hct); Masson staining with urea nitrogen (BUN), serum creatinine (SCr), hemoglobin (Hb), hematocrit (Hct); Masson staining the expression of EPO and EPOR in the kidney were observed by immunohistochemistry and Western blotting respectively. Apoptosis was detected by TUNEL staining and electron microscopy. Results: compared with the control group, the nephrotoxicity group had lower body weight, lower renal function, lower Hb and Hct, accompanied by anemia, and the renal tubulointerstitial fibrosis and apoptosis increased in the nephrotoxicity group (K0.01); EPO expression decreased significantly in the nephrotoxicity group. However, the expression of EPOR was significantly enhanced. Linear correlation analysis showed that the expression of EPO protein was negatively correlated with the number of TIF and TUNEL positive cells. Conclusion: chronic nephrotoxicity induced by CsA can decrease the expression of EPO protein in renal tissue and lead to the decrease of hematopoietic function, which may result in anemia. The decrease of EPO protein expression may be related to the apoptosis of renal tubular epithelial cells induced by CsA nephrotoxicity.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R692

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