CAJ | 학술논문

目的评价肝细胞线粒体膜通透性转换孔(mPTP)在肢体缺血后处理减轻大鼠肝缺血再灌注损伤中的作用.方法健康雄性SD大鼠48只,体重240～280 g,采用随机数字表法分为4组(n=12):假手术组(S组)、缺血再灌注组(I/R组)、肢体缺血后处理组(LIPC组)和肢体缺血后处理+苍术苷组(LIPC+APC组).I/R组、LIPC组和LIPC+APC组采用结扎支配肝左、中叶的门静脉、肝动脉30 min再灌注120 min的方法制备肝脏缺血再灌注损伤模型;LIPC组于肝脏缺血后20 min行大鼠双侧肢体缺血10 min;LIPC+APC组于肝脏缺血后20 min行大鼠双侧肢体缺血10 min,同时经阴茎静脉给予苍术苷5 mg/kg.于再灌注120 min时采集下腔静脉血3 ml测定血浆谷草转氨酶(AST)、谷丙转氨酶(ALT)的活性,随后处死大鼠取肝左叶,测定mPTP的开放程度;电镜下观察肝细胞的超微结构.结果与S组比较,其余3组血浆ALT和AST活性升高,肝细胞mPTP的开放增加(P＜0.01),肝细胞超微结构损伤明显;与I/R组比较,LIPC组和LIPC+APC组血浆ALT和AST活性降低,肝细胞mPTP的开放减少(P＜0.01),肝脏超微结构损伤减轻;与LIPC组比较,LIPC+APC组血浆ALT和AST活性升高,肝细胞mPTP的开放增加(P＜0.01).结论肢体缺血后处理通过抑制肝细胞mPTP的开放减轻大鼠肝缺血再灌注损伤.
목적 평개간세포선립체막통투성전환공(mPTP)재지체결혈후처리감경대서간결혈재관주손상중적작용.방법 건강웅성SD대서48지,체중240～280 g,채용수궤수자표법분위4조(n=12):가수술조(S조)、결혈재관주조(I/R조)、지체결혈후처리조(LIPC조)화지체결혈후처리+창술감조(LIPC+APC조).I/R조、LIPC조화LIPC+APC조채용결찰지배간좌、중협적문정맥、간동맥30 min재관주120 min적방법제비간장결혈재관주손상모형;LIPC조우간장결혈후20 min행대서쌍측지체결혈10 min;LIPC+APC조우간장결혈후20 min행대서쌍측지체결혈10 min,동시경음경정맥급여창술감5 mg/kg.우재관주120 min시채집하강정맥혈3 ml측정혈장곡초전안매(AST)、곡병전안매(ALT)적활성,수후처사대서취간좌협,측정mPTP적개방정도;전경하관찰간세포적초미결구.결과 여S조비교,기여3조혈장ALT화AST활성승고,간세포mPTP적개방증가(P＜0.01),간세포초미결구손상명현;여I/R조비교,LIPC조화LIPC+APC조혈장ALT화AST활성강저,간세포mPTP적개방감소(P＜0.01),간장초미결구손상감경;여LIPC조비교,LIPC+APC조혈장ALT화AST활성승고,간세포mPTP적개방증가(P＜0.01).결론 지체결혈후처리통과억제간세포mPTP적개방감경대서간결혈재관주손상.
Objective To evaluate the role of mitochondrial permeability transition pore (mPTP) in hepatocytes in reduction of hepatic ischemia-reperfusion (I/R) injury by limb ischemic postconditioning in rats.Methods Forty-eight healthy male Sprague-Dawley rats,weighing 240-280 g,were randomly divided into 4 groups (n =12 each) using a random number table:sham operation group (group S);I/R group;limb ischemic postconditioning group (group LIPC);limb ischemic postconditioning and atractyloside group (group LIPC + APC).In I/R,LIPC and LIPC + APC groups,I/R injury was induced by 30 min occlusion of the hepatic artery and portal vein entering the left and middle lobes of the liver,followed by 120 min of reperfusion.The animals underwent 10 min of bilateral limb ischemia starting from 20 min after liver ischemia in group LIPC.In group LIPC+APC,the animals underwent 10 min of bilateral limb ischemia starting from 20 min after liver ischemia,and atractyloside 5 mg/kg was infused simultaneously via the penile vein.Blood samples were collected from inferior vena cava at the end of reperfusion to detect plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities.The rats were sacrificed,and the left lobe of the liver was removed to detect the degree of mPTP opening and to examine the ultrastructure of hepatocytes under electron microscope.Results Compared with group S,the plasma ALT and AST activities and degree of mPTP opening were significantly increased,and the damage to the ultrastructure of hepatocytes was obvious in the other three groups.Compared with group I/R,the plasma ALT and AST activities and degree of mPTP opening were significantly decreased,and the damage to the ultrastructure of hepatocytes was reduced in LIPC and LIPC + APC groups.Compared with group LIPC,the plasma ALT and AST activities and degree of mPTP opening were significantly increased in group LIPC+APC.Conclusion Limb ischemic postconditioning reduces hepatic I/R injury through inhibiting mPTP opening in hepatocytes of rats.