Sun Qiao-ling, Chen Yi-pu, Rui Hong-liang
Graduate School, CAMS and PUMC, Beijing 100730, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2010 Apr;32(2):205-9. doi: 10.3881/j.issn.1000-503X.2010.02.016.
To establish a new rat model of chronic cyclosporine A nephrotoxicity and explore its features.
Totally 24 male SD rats were equally randomized divided into 3 groups: sham-adrenalectomized (sham-ADX) group, ADX group and ADX plus cyclosporine A (CsA) group. Rats in ADX and CsA group first underwent adrenalectomy, followed by the administration of placebo or dexamethasone, respectively. Rats in sham-ADX group received sham adrenalectomy and distilled water as control. Six weeks later, all rats were sacrificed and the following indicators were evaluated: urine protein excretion, creatinine clearance, aldosterone level in serum and urine, aldosterone level and its synthase CYP11B2 gene expression in kidney, serum natrium and potassium, urine natrium and potassium excretion, and tubulointerstitial fibrosis by masson trichrome stain.
In ADX and CsA group, serum and urine aldosterone were undetectable on the second post-operative day, with other observations including natriuresis, hyponatremia, decreased urine potassium excretion, and hyperpotassemia, suggesting that adrenals were removed intact and the adrenalectomy was successful. Rats in CsA group showed increased urine protein, decreased creatinine clearance and tubulointerstitial fibrosis, suggesting that a model of chronic CsA nephrotoxicity was successfully established. At the endpoint, serum potassium, serum aldosterone, urine potassium and urine aldosterone excretion partially retrieved. Natrium in serum and urine was not significant different between ADX group/CsA group and sham-ADX group. Local renal aldosterone and its gene expression were remarkably upregulated.
We successfully established a new rat model of chronic CsA nephrotoxicity by adrenalectomy without low sodium diet. After adrenalectomy, local renal aldosterone in kidney may compensate for circulatory aldosterone deficit to maintain electrolyte balance.
建立一种新的环孢素A慢性肾毒性大鼠模型并探讨其特征。
将24只雄性SD大鼠随机均分为3组：假肾上腺切除（假手术）组、肾上腺切除组和肾上腺切除加环孢素A（CsA）组。肾上腺切除加CsA组的大鼠先进行肾上腺切除术，然后分别给予安慰剂或地塞米松。假手术组大鼠接受假肾上腺切除术并以蒸馏水作为对照。六周后，处死所有大鼠并评估以下指标：尿蛋白排泄、肌酐清除率、血清和尿液中的醛固酮水平、肾脏中醛固酮水平及其合成酶CYP11B2基因表达、血清钠和钾、尿钠和钾排泄，以及通过Masson三色染色评估肾小管间质纤维化。
肾上腺切除加CsA组在术后第二天血清和尿液中未检测到醛固酮，其他观察结果包括利钠、低钠血症、尿钾排泄减少和高钾血症，提示肾上腺完整切除且肾上腺切除术成功。CsA组大鼠表现出尿蛋白增加、肌酐清除率降低和肾小管间质纤维化，提示成功建立了慢性CsA肾毒性模型。在实验终点，血清钾、血清醛固酮、尿钾和尿醛固酮排泄部分恢复。肾上腺切除组/CsA组与假手术组之间血清和尿液中的钠无显著差异。肾脏局部醛固酮及其基因表达显著上调。
我们通过肾上腺切除术成功建立了一种无需低钠饮食的慢性CsA肾毒性大鼠新模型。肾上腺切除术后，肾脏局部醛固酮可代偿循环醛固酮缺乏以维持电解质平衡。
