大鼠肾缺血-再灌注后JNK mRNA及蛋白表达的变化及银杏达莫注射液的干预作用  

Effect of Injection of Ginkgo Biloba Extract and Dipyridamole on JNK Activation in Rats with Renal Ischemia Reperfusion Injury

作　　者：李丹 张艳华[2] 陈少杰 虞旭光 林向东 唐兰兰[2] 王淑君[2] 王园园[2] 黎关龙[2] 王万铁[2] 

机构地区：[1]浙江省乐清人民医院肾内科,乐清325600 [2]温州医学院病理生理学教研室,温州325035

出　　处：《中国中西医结合肾病杂志》2011年第4期303-307,379,380,共7页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：温州市科技局基金资助项目(No.Y20080019)

摘　　要：目的:观察JNK在肾缺血-再灌注损伤大鼠肾组织中的表达,研究银杏达莫注射液对肾缺血-再灌注损伤的防治作用。方法:将健康雄性SD大鼠50只随机分为5组:假手术对照组(n=10),缺血-再灌注损伤模型组(n=10),银杏达莫高剂量、中剂量、低剂量组(每组10只)。对于模型组、高、中、低剂量组,切除右肾,夹闭左侧肾蒂缺血1h,移去动脉夹再灌注1h,除此之外,对于银杏达莫处理组,手术前分别按每天0.9,1.8,3.6ml/kg的剂量尾静脉注射给药1周,假手术对照组和模型组手术前按每天1.8ml/kg的剂量尾静脉注射生理盐水,给药1周。检测肾组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)的活性及血肌酐(Scr)、血尿素氮(BUN)的含量。取肾组织光镜、电镜下观察各组肾组织的形态学变化,用RT-PCR技术检测各组大鼠肾组织JNKmRNA的表达情况,Western印迹法观察p38MAPK、JNK的活化情况。结果:与假手术对照组相比,模型组大鼠Scr(214.2±40.1)μmol/L、BUN(8.75±1.28)mmol/L及MDA(11.27±2.43)nmol/mgprot含量均比假手术组增高(P<0.01),SOD(103.62±6.59)nmol/mgprot活性显著下降(P<0.01);肾组织JNKmRNA(1.38±1.36)水平显著升高(P<0.01);肾组织p-JNK蛋白水平显著上升,与模型组比较差异有统计学意义(P<0.05)。银杏达莫注射液干预后,Scr、BUN及MDA含量显著降低,SOD活性显著升高;肾组织JNKmRNA水平显著下调,与模型组比较差异有统计学意义(P<0.01);肾组织p-JNK蛋白水平显著下调,与模型组比较差异有统计学意义(P<0.05);银杏达莫不同剂量组之间差异无统计学意义。结论:银杏达莫注射液可通过降低氧自由基水平、减轻脂质过氧化反应,从而下调JNKmRNA及蛋白表达水平以改善缺血-再灌注损伤大鼠肾功能,减轻其损伤程度。Objective：To research the protection effect of Ginkgo biloba extract and Dipyridamole injection（XGD）on renal ischemia-reperfusion injury（IRI）by observing the expression of JNK on renal ischemia reperfusion injury in rat kidney tissue.Methods：Fifty healthy male SD rats were randomly divided into five groups：sham group（n=10）,IRI group（n=10）,high,middle and low dosage XGD groups（n=10,respectively）.For IRI,high,middle and low dosage XGD groups,we removed the right kidney,clamped the left renal pedicle for 1 h,then removed the arterial clip and reperfused for 1 h.Besides,for high,middle and low dosage XGD groups,before operation XGD was given by tail vein injection for a week,the dosage was 0.9,1.8,3.6 ml·kg-1·d-1,respectively.For sham group and IRI group,before operation normal saline was given by tail vein injection for a week,the dosage was 1.8 ml·kg-1·d-1.Detected malondialdehyde（MDA）content and superoxide dismutase（SOD）activity in renal tissue and serum creatinine（Scr）,blood urea nitrogen（BUN）levels.Morphologic changes of renal tissue were observed by optical and electronic microscope.Gene expression of JNK mRNA was measured by reverse transcription-polymerase chain reaction and western bloting was used to detect the protein expression and activation.Results：Compared with the sham group,the levels of Scr（214.2±40.1）,BUN（8.75±1.28）and MDA（11.27±2.43）of IRI group were significantly increased（P〈0.01）,SOD activity（103.62±6.59）was significantly decreased（P〈0.01）;JNK mRNA（1.38±1.36）expression was sifnificantly higher（P〈0.01）,the phosphorylation of JNK protein was sifnificantly increased（P〈0.05）.After intervention of XGD,contents of Scr,BUN and MDA were significantly lower,SOD activity was significantly increased;JNK mRNA expression was significantly reduced.There is statistical significance（P〈0.01）.Different XGD dosage groups showed no significant differences.Conclusion：Our data suggest that XGD reduces the expressi

关 键 词：肾 缺血-再灌注损伤 JNK 银杏达莫注射液 

分 类 号：R285.5[医药卫生—中药学]