p38MAPK和JNK在大鼠肾缺血-再灌注损伤模型中的表达及意义  

Expression of p38MAPK and JNK in the rat model of renal ischemia-reperfusion Expression of p38MAPK and JNK in the rat model of renal ischemia-reperfusion

作　　者：张艳华[1] 李丹[1] 陈少杰[1] 唐兰兰[1] 黎关龙[1] 王园园[1] 王淑君[1] 王万铁[1] 

机构地区：[1]温州医学院病理生理学教研室,浙江325035

出　　处：《中国急救医学》2011年第3期227-232,290,共7页Chinese Journal of Critical Care Medicine

基　　金：温州市科技局基金资助项目（No.Y20080019）

摘　　要：目的 观察p38MAPK、JNK在肾缺血-再灌注损伤大鼠肾组织中的表达和活化,从而探讨p38MAPK、JNK信号转导通路与肾缺血-再灌注损伤的关系.方法 用缺血1 h再灌注1 h 制备缺血-再灌注模型,20只健康雄性SD大鼠[体质量（200±20）g]随机分为假手术组（n=10）、缺血-再灌注损伤组（n=10）.检测肾组织丙二醛（MDA）浓度、超氧化物歧化酶（SOD）活性及血尿素氮（BUN）、肌酐（Cr）浓度.观察肾组织光镜、电镜下的形态学变化,用RT-PCR技术检测两组肾组织p38MAPK、JNK mRNA的表达情况,Western印迹法观察p38MAPK、JNK的活化情况.结果 缺血-再灌注损伤后,大鼠肾功能和肾小管上皮细胞明显受损,BUN、Cr、MDA浓度均高于假手术组（P〈0.01）,SOD活性低于假手术组（P〈0.01）,p38MAPK、JNK磷酸化蛋白在假手术组呈少量散在表达或不表达,缺血-再灌注损伤后磷酸化p38MAPK、JNK呈阳性表达（P〈0.01）.p38MAPK、JNK mRNA在缺血-再灌注损伤组的表达较假手术组显著增高（P〈0.01）.结论 肾缺血-再灌注可增加p38MAPK、JNK的磷酸化水平及p38MAPK、JNK mRNA的转录水平,p38MAPK、JNK可能在肾缺血-再灌注损伤中起到至关重要的作用.Objective To study the mechanisms of p38MAPK, JNK signaling pathway on renal ischemia - reperfusion injury by observing the expression and activation of p38MAPK and JNK on renal ischemia-reperfusion injury in rat kidney tissues. Methods We removed the right kidney, clamped the left renal pedicle for 1 h, then removed the arterial clip and reperfused for 1 h to prepare the ischemia- reperfusion model. 20 healthy male SD rats [ weight （200 ± 20） g ] were randomly divided into lwo groups ： control group （ normal, n = 10） , and ischemia - repeffusion injury model group （ IRI, n = 10）. Malondialdehyde （MDA） content and superoxide dismutase （SOD） activity in renal tissue and serum creatinine （Scr）, blood urea nitrogen （BUN） levels were detected. Morphologic changes of renal tissue were observed by optical and electronic microscope. Gene expression and activation of p38MAPK, JNK mRNA was measured by reverse transcription - polymerase chain reaction and Western blot. Results After ischemia- reperfusion injury, renal function and renal tubular epithelial cells was damaged, the levels of BUN, Cr, MDA were higher in IRI group than in sham operation group （P 〈 0. 01）, SOD activity was significantly decreased （P 〈 0.01 ） ; the phosphorylation of p38MAPK, JNK protein in sham group was sparse or no expression, while in the ischemia - reperfusion injury group, the phosphorylations of p38MAPK and JNK were protein -positive expression （P 〈0. 01 ）. The expressions of p38MAPK and JNK mRNA were significantly higher in ischemia - reperfusion injury group than in sham operation group （P 〈 0.01 ）. Conclusion Renal ischemia - reperfusion injury can increase the phosphorylation levels of p38MAPK, JNK and the transcription levels of p38MAPK, JNK mRNA. Our data suggest that p38MAPK and JNK may play a crucial role in renal ischemia - reperfusion injury activated by oxygen free radical（OFR）.

关 键 词：肾 缺血-再灌注损伤 P38MAPK JNK 

分 类 号：R711.3[医药卫生—妇产科学]