mito-KATP通道在利多卡因预先给药减轻大鼠肾脏缺血再灌注损伤中的作用  

Role of mitochondriai ATP-sensitive potassium channels in attenuation of renal ischemia-reperfusion injury by lidocaine pretreatment in rats

作　　者：朱小兵[1] 刘志群[1] 吴论[1] 刘志龙[2] 卫毅[2] 石翊飒[3] 张喜洋[3] 

机构地区：[1]中山市中医院麻醉科,528400 [2]甘肃省人民医院麻醉科 [3]兰州大学第二医院麻醉科

出　　处：《中华麻醉学杂志》2013年第11期1322-1325,共4页Chinese Journal of Anesthesiology

摘　　要：目的评价线粒体ATP敏感性钾通道（mito—KATP 通道）在利多卡因预先给药减轻大鼠肾脏缺血再灌注损伤中的作用。方法健康雄性Wistar大鼠60只，体重300-350g，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）夹闭双侧肾动脉60min、恢复灌注4h建立大鼠肾脏缺血再灌注损伤模型；利多卡因预先给药组（L组）夹闭双侧肾动脉前60min时静脉注射5mg／kg利多卡因，随后以2mg·kg-1·h-1速率静脉输注60min；mito—KATP通道阻断剂5-羟葵酸组（5-HD组）缺血前65min时经腹腔注射5-HD10mg／kg，余处理同I／R组；mito-KATP通道阻断剂5-羟葵酸＋利多卡因组（5-HD＋L组），缺血前65min时经腹腔注射5-HD10mg／kg，余处理同L组。再灌注4h时，取心脏血样，测定血清Cr和BUN浓度、取肾组织，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，分离肾小管上皮细胞，测定肾小管上皮细胞膜线粒体电位，光镜下观察肾组织病理学结果。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、肾小管上皮细胞膜线粒体电位降低（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、肾小管上皮细胞膜电位升高（P〈0．05），5-HD组血清Cr、BUN浓度和MDA含量，SOD活性、肾小管上皮细胞膜电位差异无统计学意义（P〉0．05）；与L组比较，5-HD＋L组血清Cr、BUN浓度和肾组织MDA含量升高，SOD活性降低、。肾小管上皮细胞膜线粒体电位降低（P〈0．05）；L组肾组织病理学损伤较I／R组和5．HD＋L组减轻。结论mito-KATP通道参与了利多卡因预先给药减轻大鼠肾脏缺血再灌注损伤的过程。Objective To evaluate the role of mitochondrial ATP-sensitive potassium （mito-KATP ） chan- nels in attenuation of renal ischemia-reperfusion （I/R） injury by lidocaine pretreatment in rats. Methods Sixty healthy male Wistar rats, weighing 300-350 g, were randomly assigned into 5 groups （ n = 12 each） using a ran- dom number table： sham operation group （group S）; renal I/R group （group I/R）; lidoeaine pretreatment group （group L） ; 5-HD （a specific blocker of the mito-KATP channel） group and 5-HD ＋ lidocaine pretreatment group （group 5-HD ＋ L）. Renal ischemia was induced by occlusion of bilateral renal arteries for 60 rain with atraumatie microelips followed by 4 h reperfusion. At 60 min before renal ischemia, lidocaine 5 mg/kg was intravenously in- jected followed by continuous infusion at 2 mg. kg- 1 . h- 1 in group L. 5-HD 10 mg/kg was injected intraperitoneally at 65 min before ischemia in group 5-HD. In 5-HD ＋ L groups, 5-HD 10 mg/kg was injected intraperitoneally at 65 rain before ischemia and the other procedures were similar to those previously described in group L. In S and I/R groups, the animals received equal volumes of normal saline instead of lidoeaine. Blood samples were obtainedat 6 h of reperfusion for determination of serum creatinine （Cr） and urea mitrogen （BUN） concentrations. Bilateral kidneys were removed for determination of mitochondrial membrane potential in the renal tubular epidural cells, malondialdehyde （MDA） content, and superoxide dismutase （SOD） activity and for microscopic examination. Re- suits Compared with group S, the serum Cr and BUN concentrations and MDA content were significantly in- creased, and SOD activity and mitochondrial membrane potential 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 sig- nificantly decreased, and SOD activity and mitochondrial membrane potential were increased in L and 5-HD ＋ L groups �

关 键 词：KATP通道 利多卡因 再灌注损伤 肾 

分 类 号：R614[医药卫生—麻醉学]