mito-KATP通道在利多卡因减轻肾缺血再灌注心肌损伤的作用

Role of mitochondrial ATP-sensitive potassium channels in myocardial damage induced by renal ischemia-reperfusion by lidocaine pretreatment in rats

目的评价线粒体ATP敏感性钾（mito-KATP）通道在利多卡因预先给药减轻肾脏缺血再灌注致大鼠心肌损伤中的作用。方法健康雄性Wistar大鼠60只,体重300~350 g,采用随机数字表法分为5组（n=12）：假手术组（S组）、肾脏缺血再灌注组（I/R组）、利多卡因组（L组）、mito-KATP通道阻断剂5-羟葵酸组（5-HD组）和mito-KATP通道阻断剂5-羟葵酸＋L组（5-HD＋L组）。夹闭双侧肾动脉60 min、恢复灌注4 h建立大鼠肾脏缺血再灌注损伤模型,术后再灌注4 h时,取心脏血样,测定血清Cr和BUN浓度,测定心肌肌钙蛋白I（c Tn I）水平,取心肌组织,分别采用黄嘌呤氧化酶法、硫代巴比妥法测定超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量。结果与S组比较,I/R组、L组、5-HD组和5-HD＋L组血清Cr、BUN浓度和MDA含量升高,SOD活性降低、c Tn I浓度升高（P〈0.05）;与I/R组比较,L组和5-HD＋L组血清Cr、BUN浓度和MDA含量降低,SOD活性升高、c Tn I浓度降低（P〈0.05）,5-HD组血清Cr、BUN浓度和MDA含量,SOD活性、c Tn I浓度差异无统计学意义（P〉0.05）;与L组比较,5-HD＋L组血清Cr、BUN浓度和肾组织MDA浓度升高,SOD活性降低、c Tn I浓度升高（P〈0.05）;L组心肌组织病理学损伤较I/R组和5-HD＋L组减轻。结论线粒体ATP敏感性钾通道参与了利多卡因预先给药减轻肾脏缺血再灌注致大鼠心肌损伤的过程。

Objective To evaluate the role of mitochondrial ATP- sensitive potassium（mito- KATP）channels inmyocardial damage induced by renal ischemia-reperfusion by lidocaine pretreatment in rats. Methods A total of 60 healthymale Wistar rats,weighing 300-350 g,were assigned into 5 groups（at 12 each）using a random number table： sham operationgroup（group S）,renal I/R group（group I/R）,lidocaine group（group LP）,5-HD（a specific blocker of the mito-KATP channel）group,and 5-HD＋lidocaine group（group 5-HD＋L）. Renal ischemia model was induced by occlusion of bilateral renal arteriesfor 60 min with atraumatic micro clips followed by 4 h reperfusion. Serum creatinine（Cr）,urea mitrogen（BUN）,and c Tn I weretested in blood samples,malondialdehyde（MDA）content and superoxide dismutase（SOD）activity were tested in myocardialtissues. Results Compared with group S,the serum Cr and BUN concentrations and MDA content were significantlyincreased,and SOD activity and c Tn I concentrations were decreased in I/R,L,5- HD and 5- HD ＋ L groups（P〈0.05）.Compared with group I/R,the serum Cr and BUN concentrations and MDA content were significantly decreased,and SODactivity and c Tn I concentrations were increased in L and 5-HD＋L groups（P〈0.05）,and there were no statistical significancein the serum Cr and BUN concentrations,MDA content,SOD activity and c Tn I concentrations in group 5- HD（P〈0.05）.Compared with group L,the serum Cr and BUN concentrations and MDA content were significantly increased,and SOD activityand c Tn I concentrations were decreased in 5-HD＋L group（P〈0.05）. The pathological damages were significantly reduced ingroup L,compared with I/R and 5- HD ＋ L groups. Conclusion Mito- KATP channels are involved in reduction of I/R-induced renal injury by lidocaine pretreatment in rats.