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  

Fasudil hydrochloride prevents cisplatin-induced renal tubular epithelial cell apoptosis via Akt activation and PTEN inhibition

作　　者：孔德阳[1] 郝建兵[1] 叶向梅[1] 唐杰[1] 包娜娜[1] 侯冬华 

机构地区：[1]哈尔滨医科大学附属第一医院肾内科,黑龙江哈尔滨150081

出　　处：《中国病理生理杂志》2015年第12期2254-2258,共5页Chinese Journal of Pathophysiology

基　　金：哈医大一院科研基金(No.2013Y01)

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(P<0.05),而p-Akt表达则显著减少(P<0.05);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(P<0.05),而p-Akt水平则显著增高(P<0.05);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。AIM： To explore the protective effect of fasudil hydrochloride against cisplatin（ CP）-induced renal tubular epithelial cell apoptosis via Akt activation and PTEN inhibition. METHODS： Healthy male Sprague-Dawley（ SD）rats were randomly divided into control group,CP group and CP ＋ fasudil group. All animals were sacrificed 96 h after injection of 0. 9% saline or CP. Blood samples and kidney tissues were collected to evaluate levels of blood urea nitrogen（ BUN）,serum creatinine（ s Cr） and morphological alteration of the kidneys,respectively. The apoptosis of renal tubular epithelium cells was detected by TUNEL. Protein levels of Rho-associated protein kinase 1（ ROCK1）,PTEN and Akt were measured by Western blotting and immunohistochemistry. The protein level of p-Akt was analyzed by Western blotting.RESULTS： Compared with control group,the s Cr and BUN levels,the expression of ROCK1 and PTEN and TUNEL-positive cells were increased,while the level of p-Akt was decreased in CP group and CP ＋ fasudil group. The histological structure of the kidneys observed by PAS staining was developed marked structural damage in CP group（ P〈0. 05）. Compared with CP group,s Cr level,the expression of ROCK1 and PTEN and TUNEL-positive cells were decreased,while the level of p-Akt was increased in CP ＋ fasudil group（ P〈0. 05）. Very little structural damage was detected in fasudil-treated groups. CONCLUSION： Fasudil hydrochloride has a protective effect on CP-induced renal tubular epithelial cell apoptosis via Akt activation and PTEN inhibition 1.

关 键 词：盐酸法舒地尔 顺铂 急性肾损伤 细胞凋亡 Rho蛋白激酶1 

分 类 号：R363.2[医药卫生—病理学]