大鼠肾缺血-再灌注后p38MAPK蛋白表达的变化及银杏达莫注射液对其的影响

Effect of Injection of Ginkgo Biloba Extract and Dipyridamole on p38MAPK Activation in Rats with Renal Ischemia Reperfusion

目的:探讨银杏达莫注射液对肾缺血-再灌注损伤的保护作用及机制。方法:肾缺血1h再灌注1h建立大鼠肾缺血再灌注损伤模型,用银杏达莫注射液分别按剂量0.9、1.8、3.6mL/kg预处理7天。通过检测肾组织丙二醛含量、超氧化物歧化酶的活性及血肌酐、血尿素氮的含量。电镜下观察各组肾组织的形态学变化,West-ern印迹法观察p38 MAPK蛋白的活化情况。结果:缺血再灌注损伤后,肾组织出现明显病理改变,肾组织丙二醛含量升高,超氧化物歧化酶活性下降,血肌酐、尿素氮水平升高,肾组织p-p38MAPK蛋白水平显著上升。银杏达莫注射液预处理能降低血肌酐、尿素氮水平及肾组织丙二醛含量,增强超氧化物歧化酶活性和下调p-p38MAPK蛋白水平,与模型组比较有显著性差异(P<0.05和P<0.01)。电镜观察肾组织的病理改变也明显好转。银杏达莫注射液不同剂量组之间无明显差异。结论:银杏达莫注射液对肾缺血再灌注损伤有良好的保护作用,其机制可能是通过清除氧自由基、减轻脂质过氧化反应而下调p38MAPK蛋白的表达以减轻再灌注损伤程度,进而大鼠肾功能。

Objective：To explore the mechanism of protective effects of Ginkgo biloba extract and Dipyridamole injection（XGD） on renal ischemia-reperfusion injury（RIRI）.Methods：The model of renal ischemia-reperfusion injury in male rats was made by removing the right renal,and clamping of left renal artery for 1 hour and 1 hour of reperfusion.The rats with pretreatment were fed with XGD respectively at the dosage of 0.9,1.8,3.6mL/kg prior to operation for a week,The content of malondialdehyde（MDA）,the activity of superoxide dismutase（SOD） in renal tissue and the levels of serum creatinine（Scr）,blood urea nitrogen（BUN） were measured.The morphologic changes of renal tissue were observed by electronic microscope.western bloting was used to detect the protein expression and activation.Results：After ischemia-reperfusion,the activity of SOD in renal tissue was decreased,however,the content of MDA and p-p38MAPK protein in renal tissue and the levels of BUN,Cr in plasma were increased.Pathological changes induced by ischemia-reperfusion in renal tissues were observed clearly.The pretreatment of rats with XGD significantly prevented reduction of SOD activity and increasing of MDA content and p-p38MAPK protein in renal tissue,decreased elevation of concentration of BUN and Cr in plasma.Pathological changes of proximal tubullar cells in rat kidneys induced by ischemia-reperfusion were also prevented by the pretreatment with XGD.Different XGD dosage groups showed no significant differences.Conclusion：XGD can protect rats from renal injuries caused by ischemia-reperfusion.The mechanism of protective effects of XGD may be related to preserving the activity of SOD and alleviating lipid peroxidation to reduce the expression of p-p38MAPK protein to improve the ischemia-reperfusion injury in rat kidney function and to reduce the damage.