促红细胞生成素及其受体在慢性环孢素A肾毒性大鼠肾中的表达

发布时间：2018-10-19 08:49

【摘要】：目的：探讨1)环孢素A (Cyclosporine A, CsA)肾毒性是否可引起模型贫血；2)在慢性CsA肾毒性肾中促红细胞生成素(Erythropoietin, EPO)及促红细胞生成素受体(EPOR)的表达情况。方法：健康Sprague-Dawley大鼠分别给予皮下注射CsA (15mg. kg-1. d-1)和橄榄油(1mL. kg-1, d-1)4周后,建立慢性CsA肾毒性组和对照组。处死前检测各组大鼠的尿素氮(BUN)、血肌酐(SCr)、血色素(Hb)、红细胞压积(Hct); Masson染色法确定肾小管间质纤维化程度；免疫组织化学染色和免疫印迹法分别观察肾内EPO及EPOR的表达；TUNEL染色和电子显微镜检测细胞凋亡。结果：与对照组相比,肾毒性组体重下降、肾功能低下、Hb和Hct的下降,伴有贫血发生；肾毒性组肾小管间质带状纤维化、细胞凋亡增加(K0.01); EPO在肾毒性组中的表达明显减少,而EPOR的表达却明显加强。直线相关分析表明,EPO蛋白表达与TIF和TUNEL阳性细胞数呈负向相关。结论：CsA所致的慢性肾毒性使得肾组织内EPO蛋白表达减少,从而导致造血功能下降,进而产生贫血。EPO蛋白表达减少可能与CsA肾毒性所致肾小管上皮细胞凋亡有相关性。
[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.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R692

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