目的:探讨细胞色素C对庆大霉素致大鼠肾小管上皮细胞毒性的影响及其可能的作用机制.方法:取大鼠随机分为溶媒对照组、庆大霉素组、庆大霉素+细胞色素C组,每组10只,前2组分别腹腔注射生理盐水和庆大霉素(100 mg·kg-1·d-1),第3组先静脉注射细胞色素C 100 mg·kg-1·d-1,30 min后腹腔注射庆大霉素100 mg·kg-1.d-1.单剂量给药后24h处死大鼠,以荧光偏振免疫发光技术测定后2组大鼠肾脏中庆大霉素的含量,用TUNEL法检测肾小管上皮细胞凋亡情况,用MIAS医学图像分析系统计算凋亡阳性细胞数密度,以苏木精-伊红染色法观察肾脏组织病理学变化.结果:与溶媒对照组比较,庆大霉素组肾小管上皮细胞凋亡的阳性细胞数密度明显增加(P＜0.01)；与庆大霉素组比较,庆大霉素+细胞色素C组肾脏中庆大霉素的含量降低了33.86％( (335.16±99.18) μg·g-1 vs.(221.67±71.12)μg·g-1),肾小管上皮细胞凋亡的阳性细胞数密度明显下降((637.78±169.64)n·mm-2 vs.(404.75±135.57) n·mm-2,P＜0.05),肾小管上皮细胞水肿、空泡变性、肾间质内炎细胞浸润、肾小球充血肿胀等均有所好转.结论:细胞色素C可能通过抑制庆大霉素在肾脏中蓄积来减轻其肾毒性.%OBJECTIVE: To evaluate the effect of cytochrome C on rat renal tubular epithelial cell toxicity induced by gentami-cin and its possible mechanism. METHODS: Rats were randomly divided into solvent control group, gentamicin group and genta-micin plus cytochrome C group with 10 animals in each group. The former 2 groups were given intraperitoneal injection of normal saline and gentamicin (100 mg·kg-1·d-1) respectively. The third group was given intraperitoneal injection of cytochrome C 100 mg· kg1·d-1 and then given intraperitoneal injection of gentamicin 100 mg·kg-1·d-1 30 min later. Rats were sacrificed 24 hours after the single dosing, and the content of gentamicin in kidney was determined by Fluorescence polarization immunoassay chemilumines-cence technique in the latter two groups. The apoptotic renal tubular epithelial cells were determined by TUNEL assay, and the positive number of apoptotic renal tubular epithelial cells was calculated by Medical Image Analysis System (MIAS). The histopatholog-ic changes of renal tissue were observed by HE staining. RESULTS: Compared with solvent control group, the positive number of apoptotic renal tubular epithelial cells in gentamicin group increased (P＜0.01). Compared with the gentamicin group, the content of gentamicin in kidneys of the gentamicin plus cytochrome C group declined by 33.86% ((335.16 ± 99.18) μg·g-1 vs. (221.67 ± 71.12) ng·g-1); the positive number of apoptotic renal tubular epithelial cells decreased significantly ((637.78 ± 169.64) n-mm-2 vs. (404.75 ± 135.57) n-mm-2, P＜0.05); renal tubular epithelial cells swelling, vacuolar degeneration, tubulointerstitial inflammatory cell infiltration and glomerulus engorgement and swelling were all improved to some extent. CONCLUSION: Cytochrome C can inhibit nephrotoxicity by reducing the amount of gentamicin accumulated in kidney.
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