大鼠肾缺血-再灌注损伤后p38MAPK mRNA表达的变化及银杏达莫注射液对其的影响  

Effect of Ginkgo biloba injection and dipyridamole on p38MAPK 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] 石璐[2] 贾旭广[2] 王万铁[2] 

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

出　　处：《浙江医学》2010年第11期1635-1640,共6页Zhejiang Medical Journal

基　　金：温州市科技计划项目（Y20080019）

摘　　要：目的观察p38MAPK在缺血-再灌注损伤（IRI）大鼠肾组织中的表达，研究银杏达莫注射液对肾IRI的保护作用及机制。方法将健康雄性SD大鼠50只随机分为5组：假手术对照组，IRI模型组，银杏达莫注射液高、中、低剂量组，每组各10只。IRI模型组和高、中、低剂量组，手术切除右肾，夹闭左侧肾蒂缺血1h，移去动脉夹再灌注1h，除此之外，对于银杏达莫注射液处理组，术前分别按09、18、36mg·kg^-1·d^-1的剂量尾静脉注射给药1周。假手术对照组和IRI模型组术前按18mg·kg^-1·d^-1的剂量尾静脉注射09％氯化钠注射液，给药1周。1周后处死大鼠检测其肾组织丙二醛（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、电镜下观察肾组织的形态学变化，用RT-PCR技术检测各组大鼠肾组织p38MAPK mRNA的表达情况。结果与假手术对照组相比，模型组大鼠Cr（214.2±40.1）μmol／L、BUN（8．75±1.28）mmol／L及MDA（11．27±2．43）nmol／mg—prot含量均比假手术对照组增高（P〈0.01），SOD（103．62±6.59）U／mgprot活性显著下降（P〈0.01）；肾组织p38MAPK mRNA（1.38±1.36）水平显著升高（P〈0．01）.银杏达莫注射液处理各组Scr、BUN及MDA含量显著降低，SOD活性显著升高；肾组织p38MAPK mRNA表达水平显著下调，与模型组比较差异有统计学意义（P〈0．01）；银杏达莫注射液处理各组之间无明显差异。结论银杏达莫注射液可通过降低氧自由基水平从而下调p38MAPK mRNA的表达以改善IRI大鼠肾功能，减轻其损伤程度。Objective To investigate the protective effect of Ginkgo biloba extract and dipyridamole injection （XGD） on renal ischemia-reperfusion injury （IRI） in rats. Methods Fifty male SD rats were randomly divided into 5 groups with 10 animals in each： sham group, IRI group, high, middle and low dosage XGD groups. For IRI , high, middle and low dosage XGD groups, we removed the right kidney, clamped the left renal pedicle for lh, then removed the arterial clip for lh. For XGD groups, before operation XGD （0.9, 1.8 and 3.6mg/kg） was administrated by tail vein injection for a week; for sham group and IRI group 1.8 mg/kg.d normal saline was given instead. Malondialdehyde （MDA） content and superoxide dismutase （SOD） activity in renal tissue were detected and serum creatinine （Scr）, blood urea nitrogen （BUN） levels were measured. Morphologic changes of renal tissue were observed by optical and electron microscope. Gene expression of JNK mRNA was measured by reverse transcription-poly- merase chain reaction. 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） decreased （P 〈0.01）; JNK mRNA （ 1.38 ±1.36 ）expression was significantly higher （P 〈0.01）, the phosphorylation of p38MAPK was skjnificantly increased （P 〈0.01）. After intervention of XGD, compared to sham group Scr, BUN and MDA levels in XGD groups were significantly lower, SOD activity increased; JNK mRNA expression was significantly reduced （ all P 〈0.01 ）. Different XGD dosage： groups showed no significant differences. Conclusion Results suggest that XGD reduces the expression of JNK mRNA by inhibiting oxygen free radical （OFR ） to protect kidney from IRI injuries in rats.

关 键 词：肾 缺血-再灌注损伤 P38MAPK 银杏达莫注射液 

分 类 号：R692[医药卫生—泌尿科学]