高能冲击波对肾脏钙离子腺苷三磷酸酶活性的影响及川芎嗪的保护作用

摘要

目的 观察高能冲击波对肾脏钙离子腺苷三磷酸酶(Ca2+-ATPase)活性的影响及川芎嗪的保护作用,探讨高能冲击波肾损伤机制.方法 30只健康家兔制成单肾动物模型,按完全随机设计法分为对照组10只、高能冲击波组10只和川芎嗪组10只,对照组、高能冲击波组分别静脉注射等量生理盐水,高能冲击波冲击肾脏前3天,川芎嗪组静脉注射川芎嗪;冲击肾脏24h后,光学法检测肾细胞膜和线粒体膜Ca2+-ATPase活性;采用原位缺口末端标记法和流式细胞术检测凋亡细胞;采用生化分析测定内生肌酐清除率.结果 与对照组比较,高能冲击波组肾细胞膜和线粒体膜Ca2+-ATPase活性均降低(P<0.05,P<0.01)、细胞凋亡率增加(P<0.01)、内生肌酐清除率降低(P<0.01);川芎嗪组肾细胞膜Ca2+-ATPase活性和内生肌酐清除率变化不明显(P＞0.05),线粒体膜Ca2+-ATPase活性降低(P<0.05)、细胞凋亡率增加(P<0.05),但幅度明显小于高能冲击波组.结论 高能冲击波冲击肾脏后肾脏Ca2+-ATPase活性降低是发生肾细胞凋亡导致肾功能损伤的重要机制,川芎嗪有改善肾功能的作用,与其阻制肾脏Ca2+-ATPase活性降低、抗细胞凋亡有关.%Objective To observe the effects of high energy shock wave on Ca2+-ATPase activity in rabbit renal tissues with and protective effects of ligustrazine. Methods Thirty healthy rabbits were made into the mono-nephron models and then divided into 3 groups: control group, HESW group and HESW plus ligustrazine pretreated group. Rabbit kidney tissues were analyzed 24 hours after HESW. The activity of Ca2+-ATPase in cell membranes and mitochondriat fractions in renal tissue were analyzed with optical method. Cell apoptosis was detected by TdT-mediated dUTP Nick End Labelling (TUNEL) and flow cytometry. The variations of creatinine clearance (CCr) were observed.Results Compared with the control group, The activity of Ca2+-ATPase in cell membranes and mitochondrial fractions reduced, the rate of apoptosis increased and CCr reduced significantly in the HESW group. The activity of Ca2+-ATPase in cell membranes and CCr showed no significant difference between the HESW and ligustrazine pretreated group and the control group. The activity of Ca2+-ATPase reduced in mitochondrial fractions (P＜0.05)and cell apoptosis rate were significantly higher (P＜0.05) in the HESW plus ligustrazine pretreated group than the control group, but showed the highest level in the HESW group. Conclusion Ca2+-ATPase reduction and cell apoptosis increases are important mechanisms in the kidney function damage caused by HEWS. Lignstrazine can improve kidney function by suppressing kidney Ca2+-ATPase activity reduce and cell apoptosis.