中华肝胆外科杂志
中華肝膽外科雜誌
중화간담외과잡지
CHINESE JOURNAL OF HEPATOBILIARY SURGERY
2009年
4期
288-291
,共4页
史卫海%戎亚雄%孙亚伟%徐学忠%李文美
史衛海%戎亞雄%孫亞偉%徐學忠%李文美
사위해%융아웅%손아위%서학충%리문미
肝硬化%缺血顶处理%缺血/再灌注%线粒体ATP敏感性钾通道%二氮嗪%大鼠
肝硬化%缺血頂處理%缺血/再灌註%線粒體ATP敏感性鉀通道%二氮嗪%大鼠
간경화%결혈정처리%결혈/재관주%선립체ATP민감성갑통도%이담진%대서
Liver cirrhosis,Ischemia/reperfusion injury%Ischemic preconditioning%Mitochondrial ATP-sensitive potassium channels%Diazoxide%Rat
目的 研究缺血预处理(IP)对肝硬化大鼠肝脏缺血/再灌注(I/R)损伤的保护作用,探讨线粒体ATP敏感性钾通道(mitoKATP通道)在这种保护机制中的作用.方法 复制雄性肝硬化SD大鼠,随机分为6组(每组8只).IP组以肝缺血5 min再灌注10 min作预处理;IP+5-HD组是在IP组基础上,使用微量注射泵经大鼠门静脉注射mitoKATP通道特异性阻滞剂5-HD进行预处理;DE组以静脉注射mitoKATP通道选择性开放剂DE作为预处理;DE+5-HD组是在DE组基础上再予静脉注射5-HD进行预处理;对照组(C组)以静脉注射等量生理盐水作为预处理;上述5组均在预处理后行肝缺血45 min再灌注60 min;缺血方式为70%肝脏热缺血.假手术组(S组)仅行开腹,不作任何其它处理.完成预定实验操作后分别取血用于血清谷丙转氨酶(ALT)与乳酸脱氢酶(LDH)检测,切取肝组织用于测定ATP酶活力、超氧化物岐化酶(SOD)活性、丙二醛(MDA)含量、湿重/干重(W/D)的测定及观察显微、超微结构变化.结果 C组ATP酶活性与肝损伤指标ALT与LDH活性、MDA含量与W/D比值均明显高于S组(P<0.01),肝脏在光镜与电镜下的显微与超微结构损伤明显;IP组与DE组的各项肝组织损伤指标均明显好于C组,ATP酶活性低于C组(P<0.05,P<0.01),而IP+5-HD组、DE+5-HD组的肝损伤指标分别差于IP组、DE组,ATP酶活性高于IP组、DE组(P<0.05,P<0.01);在SOD活性方面,C组明显低于S组(P<0.01),IP组低于S组,高于C组(P<0.01).DE组与C组相比无差异,IP+5-HD组、DE+5-HD组SOD活性分别与lP组、DE组相比无差异(P>0.05).结论 mitoKATP通道参与IP抗肝硬化大鼠肝I/R损伤的保护效应,其作用可能与下调肝组织ATP酶活性,减少ATP大量分解,改善肝能量代谢,增加能量储备;提高肝脏的抗氧化能力;改善肝组织微循环,减轻肝脏水肿有关.
目的 研究缺血預處理(IP)對肝硬化大鼠肝髒缺血/再灌註(I/R)損傷的保護作用,探討線粒體ATP敏感性鉀通道(mitoKATP通道)在這種保護機製中的作用.方法 複製雄性肝硬化SD大鼠,隨機分為6組(每組8隻).IP組以肝缺血5 min再灌註10 min作預處理;IP+5-HD組是在IP組基礎上,使用微量註射泵經大鼠門靜脈註射mitoKATP通道特異性阻滯劑5-HD進行預處理;DE組以靜脈註射mitoKATP通道選擇性開放劑DE作為預處理;DE+5-HD組是在DE組基礎上再予靜脈註射5-HD進行預處理;對照組(C組)以靜脈註射等量生理鹽水作為預處理;上述5組均在預處理後行肝缺血45 min再灌註60 min;缺血方式為70%肝髒熱缺血.假手術組(S組)僅行開腹,不作任何其它處理.完成預定實驗操作後分彆取血用于血清穀丙轉氨酶(ALT)與乳痠脫氫酶(LDH)檢測,切取肝組織用于測定ATP酶活力、超氧化物岐化酶(SOD)活性、丙二醛(MDA)含量、濕重/榦重(W/D)的測定及觀察顯微、超微結構變化.結果 C組ATP酶活性與肝損傷指標ALT與LDH活性、MDA含量與W/D比值均明顯高于S組(P<0.01),肝髒在光鏡與電鏡下的顯微與超微結構損傷明顯;IP組與DE組的各項肝組織損傷指標均明顯好于C組,ATP酶活性低于C組(P<0.05,P<0.01),而IP+5-HD組、DE+5-HD組的肝損傷指標分彆差于IP組、DE組,ATP酶活性高于IP組、DE組(P<0.05,P<0.01);在SOD活性方麵,C組明顯低于S組(P<0.01),IP組低于S組,高于C組(P<0.01).DE組與C組相比無差異,IP+5-HD組、DE+5-HD組SOD活性分彆與lP組、DE組相比無差異(P>0.05).結論 mitoKATP通道參與IP抗肝硬化大鼠肝I/R損傷的保護效應,其作用可能與下調肝組織ATP酶活性,減少ATP大量分解,改善肝能量代謝,增加能量儲備;提高肝髒的抗氧化能力;改善肝組織微循環,減輕肝髒水腫有關.
목적 연구결혈예처리(IP)대간경화대서간장결혈/재관주(I/R)손상적보호작용,탐토선립체ATP민감성갑통도(mitoKATP통도)재저충보호궤제중적작용.방법 복제웅성간경화SD대서,수궤분위6조(매조8지).IP조이간결혈5 min재관주10 min작예처리;IP+5-HD조시재IP조기출상,사용미량주사빙경대서문정맥주사mitoKATP통도특이성조체제5-HD진행예처리;DE조이정맥주사mitoKATP통도선택성개방제DE작위예처리;DE+5-HD조시재DE조기출상재여정맥주사5-HD진행예처리;대조조(C조)이정맥주사등량생리염수작위예처리;상술5조균재예처리후행간결혈45 min재관주60 min;결혈방식위70%간장열결혈.가수술조(S조)부행개복,불작임하기타처리.완성예정실험조작후분별취혈용우혈청곡병전안매(ALT)여유산탈경매(LDH)검측,절취간조직용우측정ATP매활력、초양화물기화매(SOD)활성、병이철(MDA)함량、습중/간중(W/D)적측정급관찰현미、초미결구변화.결과 C조ATP매활성여간손상지표ALT여LDH활성、MDA함량여W/D비치균명현고우S조(P<0.01),간장재광경여전경하적현미여초미결구손상명현;IP조여DE조적각항간조직손상지표균명현호우C조,ATP매활성저우C조(P<0.05,P<0.01),이IP+5-HD조、DE+5-HD조적간손상지표분별차우IP조、DE조,ATP매활성고우IP조、DE조(P<0.05,P<0.01);재SOD활성방면,C조명현저우S조(P<0.01),IP조저우S조,고우C조(P<0.01).DE조여C조상비무차이,IP+5-HD조、DE+5-HD조SOD활성분별여lP조、DE조상비무차이(P>0.05).결론 mitoKATP통도삼여IP항간경화대서간I/R손상적보호효응,기작용가능여하조간조직ATP매활성,감소ATP대량분해,개선간능량대사,증가능량저비;제고간장적항양화능력;개선간조직미순배,감경간장수종유관.
Objective To investigate whether the mitochondrial ATP-sensitive potassium(mi-toKATP) channels be concerned with the protection of ischemic preconditioning(IP)on liver ischemia/reperfusion(I/R)iniury in rats with cirrhosis.Methods Five groups of SD rats with liver cirrhosis(n=8 each)were pretreated with:5 min period of liver ischemia(IP group),IP plus 5-HD,a selective mitoKATP channels inhibitor 5-hydroxydecanoate(IP+5-HD group),DE,a selective mitoKATP chan-nels opener(DE group),DE plus 5-HD(DE+5-HD group),and with saline(control group).The pretreated rats were subjected to 45 min sustained liver ischemia followed by 60 min reperfusion.All rats were SLIbiected to 70% liver warm ischemia.In addition,the sixth group was established(sham group,n=8),in which only anesthesia and laparotomy was performed.Finally,blood and liver sam-pies were obtained to determine the biochemistry and pathology of the liver.Results The indexes of ATPase and the Iiver injury indexes including ALT,LDH,MDA and W/D were higher in C group than in S group(P<0.01).There were also severe histological and ultra structure damages in C group.The activity of ATPase was lower and all the injury indexes in IP group and DE group were better than those in C group(P<0.05 or P<0.01).IP+5-HD group and DE+5-HD group had the adverse changes as compared with DE group(P<0.05 or P<0.01).The activity of SOD in IP group was higher than that in C group(P<0.01).whereas there was no significant difference between DE and C group,DE and DE+5-HD group.IP and lP+5-HD group(P>0.05).Conclusion The pro-tection of IP on liver I/R injury in rats with cirrhosis is correlated with the opening of mitoKATP chan-nels,possibly due to inhibited activity of ATPase.It can decrease the decompsiton of ATP,induce a-gainst oxidizing injury.improve liver microcirculation and reduce degree of hepatic tissue edema.DE can mimic the protection of IP.
