盐酸法舒地尔通过活化Akt与抑制PTEN减轻顺铂导致的肾小管上皮细胞凋亡

发布时间：2018-03-22 07:28

本文选题：盐酸法舒地尔　切入点：顺铂　出处：《中国病理生理杂志》2015年12期 　论文类型：期刊论文

【摘要】：目的:探讨盐酸法舒地尔(fasudil)能否通过活化Akt并抑制PTEN减轻顺铂(CP)导致的肾小管上皮细胞凋亡。方法:健康雄性SD大鼠随机分为3组(每组12只),包括正常对照(control)组、CP组及CP+fasudil组。生理盐水或顺铂腹腔注射96 h后处死SD大鼠,留取血液和肾脏组织,检测血尿素氮(BUN)、血清肌酐(s Cr)水平。PAS染色光镜观察肾脏形态结构的变化;TUNEL染色检测肾小管上皮细胞凋亡;分别采用Western blotting法和/或免疫组化技术检测Rho蛋白激酶1(ROCK1)、PTEN、Akt蛋白表达变化及磷酸化Akt(p-Akt)水平。结果:与control组比较,CP组与CP+fasudil组大鼠的BUN及s Cr水平、凋亡细胞阳性率、ROCK1及PTEN蛋白表达均显著升高(P0.05),而p-Akt表达则显著减少(P0.05);PAS染色光镜示CP组肾脏组织结构出现明显损伤性变化;与CP组比较,CP+fasudil组的s Cr水平、凋亡细胞阳性率、ROCK1及PTEN蛋白表达均显著下调(P0.05),而p-Akt水平则显著增高(P0.05);此外,肾脏病理损伤减轻。结论:盐酸法舒地尔可以减轻顺铂引起肾小管上皮细胞凋亡,其机制可能与活化Akt及抑制PTEN蛋白表达相关。
[Abstract]:Objective: to investigate whether fasudil hydrochloride can attenuate apoptosis of renal tubular epithelial cells induced by cisplatin by activating Akt and inhibiting PTEN. Methods: healthy male Sprague-Dawley rats were randomly divided into 3 groups (12 rats in each group, including normal control). SD rats were killed after 96 h intraperitoneal injection of normal saline or cisplatin. Blood and renal tissues were collected, blood urea nitrogen bun, serum creatinine creatinine Cr (Cr) were detected. The changes of renal morphology and structure were observed under light microscope. Tunel staining was used to detect the apoptosis of renal tubular epithelial cells. Western blotting method and / or immunohistochemical technique were used to detect the expression of Rho protein kinase 1rokinase 1, PTENTENT protein, and the phosphorylated Akttr-Akt. Results: compared with the control group, the BUN and sCr levels in the CP group and CP fasudil group were compared. The positive rate of apoptotic cells and the expression of ROCK1 and PTEN protein were significantly increased, while the expression of p-Akt was significantly decreased in the CP group by light microscopy with p0.05 pas staining, and the level of sCr in the CP fasudil group was higher than that in the CP fasudil group, and the positive rate of apoptotic cells was significantly higher than that in the CP group, and the expression of pas in the CP group was significantly lower than that in the CP group. The positive rate of apoptotic cells and the expression of PTEN and ROCK1 were significantly down-regulated, while the level of p-Akt was significantly increased. In addition, renal pathological damage was alleviated. Conclusion: cisplatin can reduce apoptosis of renal tubular epithelial cells induced by cisplatin. The mechanism may be related to activation of Akt and inhibition of PTEN protein expression.
【作者单位】：哈尔滨医科大学附属第一医院肾内科;
【基金】：哈医大一院科研基金(No.2013Y01)
【分类号】：R965

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