CAJ | 학술논문

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Wiser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)夹闭双侧肾动脉60 min、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60 min时静脉注射5 mg/kg利多卡因,随后以2 mg·kg-·h-1速率静脉输注60 min;mito-KATP通道阻断剂5-羟葵酸组(5-HD组)缺血前65 min时经腹腔注射5-HD 10 mg/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65 min时经腹腔注射5-HD 10 mg/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.
목적 평개선립체ATP민감성갑통도(mito-KATP통도)재리다잡인예선급약감경대서신장결혈재관주손상중적작용.방법 건강웅성Wiser대서60지,체중300 ～ 350 g,채용수궤수자표법분위5조(n=12):가수술조(S조);신장결혈재관주조(I/R조)협폐쌍측신동맥60 min、회복관주4h건립대서신장결혈재관주손상모형;리다잡인예선급약조(L조)협폐쌍측신동맥전60 min시정맥주사5 mg/kg리다잡인,수후이2 mg·kg-·h-1속솔정맥수주60 min;mito-KATP통도조단제5-간규산조(5-HD조)결혈전65 min시경복강주사5-HD 10 mg/kg,여처리동I/R조;mito-KATP통도조단제5-간규산+리다잡인조(5-HD+L조),결혈전65 min시경복강주사5-HD 10 mg/kg,여처리동L조.재관주4h시,취심장혈양,측정혈청Cr화BUN농도、취신조직,분별채용황표령양화매법、류대파비타법측정초양화물기화매(SOD)활성、병이철(MDA)함량,분리신소관상피세포,측정신소관상피세포막선립체전위,광경하관찰신조직병이학결과.결과 여S조비교,I/R조、L조、5-HD조화5-HD+L조혈청Cr、BUN농도화MDA함량승고,SOD활성강저、신소관상피세포막선립체전위강저(P＜0.05);여I/R조비교,L조화5-HD+L조혈청Cr、BUN농도화MDA함량강저,SOD활성승고、신소관상피세포막전위승고(P＜0.05),5-HD조혈청Cr、BUN농도화MDA함량,SOD활성、신소관상피세포막전위차이무통계학의의(P＞0.05);여L조비교,5-HD+L조혈청Cr、BUN농도화신조직MDA함량승고,SOD활성강저、신소관상피세포막선립체전위강저(P＜0.05);L조신조직병이학손상교I/R조화5-HD+L조감경.결론 mito-KATP통도삼여료리다잡인예선급약감경대서신장결혈재관주손상적과정.
Objective To evaluate the role of mitochondrial ATP-sensitive potassium (mito-KATP) channels 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 random number table:sham operation group (group S); renal I/R group (group I/R); lidocaine 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 min with atraumatic microclips followed by 4 h reperfusion.At 60 min before renal ischemia,lidocaine 5 mg/kg was intravenously injected 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 min 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 lidocaine.Blood samples were obtained at 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.Results Compared with group S,the serum Cr and BUN concentrations and MDA content were significantly increased,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 significantly decreased,and SOD activity and mitochondrial membrane potential were increased in L and 5-HD + L groups (P ＜ 0.05),and no significant changes were found in the serum Cr and BUN concentrations,MDA content,SOD activity and mitochondrial membrane potential 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 activity and mitochondrial membrane potential were decreased in 5-HD + L group (P ＜ 0.05).The pathological changes were significantly reduced in group L as 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.