川芎嗪干预肾缺血再灌注损伤时内皮素-1、一氧化氮和超微结构变化

Effect of Ligustrazine on the Changes of Endothelin-1 Nitric Oxide and Ultrastructure during Renal Ischemia Reperfusion Injury in Rabbits

目的:观测兔肾缺血再灌注损伤时内皮素-1(ET-1)、一氧化氮(NO)和超微结构的变化,探讨川芎嗪的干预作用及机制。方法:日本大耳白兔30只,随机均分为3组:假手术组(对照组),缺血再灌注组(再灌注组),缺血再灌注+川芎嗪注射液组(川芎嗪组)。复制在体兔肾缺血再灌注损伤模型,在缺血前、缺血1 h、再灌注5 h分别经颈总动脉抽血检测ET-1和NO含量;实验结束时取肾组织检测ET-1和NO含量,电镜下观察超微结构变化。结果:①再灌注组和川芎嗪组缺血和再灌注后血浆ET-1含量均显著高于对照组(均P<0.01),而川芎嗪组均显著低于再灌注组(均P<0.01)。再灌注组缺血和再灌注后血浆NO含量均明显低于对照组(均P<0.01),而川芎嗪组均显著高于再灌注组(均P<0.01)。②与对照组相比,再灌注组肾组织ET-1含量明显升高,NO含量显著降低(均P<0.01);川芎嗪组ET-1含量差异无统计学意义(P>0.05),而NO含量明显降低(P<0.05)。与再灌注组相比,川芎嗪组肾组织ET-1含量显著降低,NO含量明显升高(均P<0.01)。③再灌注组肾小球毛细血管、内皮细胞、脏层上皮细胞和近曲小管上皮细胞超微结构严重损害,川芎嗪组大部分肾组织上述部位存在不同程度损伤性改变,但均比再灌注组明显减轻。结论:川芎嗪能抑制肾缺血再灌注损伤时肾组织过度产生ET-1,能使NO分泌增加,遏制无复流现象,同时明显减轻超微结构的严重损害,对肾缺血再灌注损伤具有防治作用。

Objective ： To investigate the changes of endothelin - 1 （ ET - 1 ）, nitric oxide （NO） and uhrastructure during renal ischemia reperfusion injury. To determine the effects of ligustrazine on renal ischemia reperfusion injury and its mechanisms. Methods.Thirty rabbits were divided averagely into three groups randomly ：sham operation group（ C group）, ischemia reperfusion group（ IR group）and ischemia reperfusion plus ligustrazine injection group（ LZ group）. The renal ischemia reperfusion injury model of rabbit was constituted in vivo. The blood plasma was gathered from common carotid artery at times：pre -ischemia,ischemia 1 h,reperfusion 5 h were tested for the contents of ET - 1 and NO. The kidney tissue sampled at the end of experiment was assayed for the contents of ET - 1 and NO simultaneously, and were observed for uhrastructure changes under electronic microscope. Results ： ①The content of ET - 1 at plasma in both IR group and LZ group after ischemia and reperfusion were significant higher than that in C group （ all P 〈 0.01 ）, however, in LZ group it was all significant lower compared with 1R group（ all P 〈0.01 ）. The content of NO of plasma at IR group after ischemia and reperfusion were significant lower than that in C group（ all P 〈 0.01 ）, and that in IZ group was significant higher compared with IR group（ all P 〈0.01 ）. ②As compared with C group,content of ET - 1 in kidney tissue was increased remarkably, content of NO was decreased significantly in IR group （ all P 〈 0.01 ）, while, content of ET - 1 in kidney tissue had no significant difference （ P 〉 0.05 ）, content of NO was decreased significantly in LZ group （ P 〈 0.05 ）. For LZ group, as compared with IR group, kidney tissue content of ET - 1 decreased significantly, content of NO elevated remarkably（all P〈0.01）. ③There were serious abnormal ultrastructure damages of glomerular capillary,endotbeliocyte,podocyte, and epithelial cells of proximal convoluted tubule in IR group. Renal tissue uhrastructure injuries in LZ group were obviously alleviated as compared to IR group. Conelusion：Ligustrazine can suppress ET - 1 overproduction and increase NO release from kidney tissue during renal ischemia reperfusion injury, so restrain no - reflow phenomenon can mitigate the abnormal changes of uhrastructure in kidney tissue,which can prevent renal ischemia reperfusion injury.