摘要
探讨盐酸法舒地尔防治脓毒血症大鼠急性肾损伤(AKI)的作用机制。腹腔注射内毒素(LPS)建立AKI模型,健康雄性Wister大鼠65只随机分为空白对照组、AKI模型组和治疗组,并观察6个时间点(1、6、12、24、48、72 h)各组血清肌酐(CRE)、尿素氮(BUN)、内皮素-1(ET-1)的水平变化及肾组织病理改变;并采用免疫组化法检测肾组织Rho激酶-Ⅰ(ROCK-Ⅰ)的表达。结果表明:(1)AKI模型组ET-1及ROCK-Ⅰ于1 h后明显升高(P<0.01),并于12 h达高峰;治疗6、12、24 h组ET-1及ROCK-Ⅰ均低于模型组(P<0.01)。(2)AKI模型组肾小管坏死评分于1 h后明显高于对照组及治疗组(P<0.05),并于24 h达高峰。(3)AKI模型组BUN、CRE于6 h后明显升高(P<0.01),并于24 h达高峰,治疗12、24 h组BUN、CRE均低于模型组(P<0.01)。盐酸法舒地尔可能通过阻断Rho/Rho激酶通路减少ET-1的产生及释放,减轻肾内动脉收缩对肾组织损伤,防治脓毒血症诱导的AKI。
Investigated the effect of Fasudil hydrochloride（Fasudil） prevented acute renal injury in rats caused by sepsis.Established acute renal injury model by intraperitoneal injection of lipopolysaccharide,Sixtyfive male Wister rats were randomly divided into three groups：control group,AKI group and treatment group,the levels of cretonne（CRE）blood urea nitrogen（BUN） Endothelin-1（ET-1） and renal pathological change were observed at 1 h,6 h,12 h,24 h,48 h,72 h;the expressions of Rho kinases-Ⅰ（ROCK-Ⅰ） in renal with immune-histochemisal method was observed.Results showed that（1）The levels of ET-1 and ROCK-Ⅰ significantly increased at 1 h（P0.01）,peaked at 12 h in AKI group.The levels of ET-1 and ROCK-Ⅰat 6 h,12 h,24 h of treatment group were lower than AKI group（P0.01）.（2）The levels of tubular necrosis score in AKI group were more higher than that of control group and treatment group（P0.05）.（3）The levels of CRE and BUN significantly increased at 6 h（P0.01）,peaked at 24 h in AKI group.The levels of BUN and CRE at 12 h,24 h of treatment group were lower than that of AKI group（P0.01）.Fasudil may reduce the expression of ET-1 by attenuation of Rho/Rho kinase signaling,hence its protection protect against LPS-induced AKI in rats.
出处
《生物医学工程研究》
2010年第3期197-201,共5页
Journal Of Biomedical Engineering Research
基金
济南军区后勤重点科研课题(项目编号07-0168)
