中国医师杂志
中國醫師雜誌
중국의사잡지
JOURNAL OF CHINESE PHYSICIAN
2013年
z1期
26-28
,共3页
IκB激酶%核因子-κB%再灌注损伤%肝脏
IκB激酶%覈因子-κB%再灌註損傷%肝髒
IκB격매%핵인자-κB%재관주손상%간장
I kappa B kinase%NF-κB%Reperfusion injury%Liver
目的 探讨IκB激酶在肝脏缺血再灌注(HIR)中的作用.方法 Wister大鼠随机分为:对照组;缺血再灌注组(HIR组);PDTC保护组(HIR+ PDTC组).HIR组将肝左叶及肝中叶入肝血流阻断60min后再灌注;保护组先经阴茎背静脉注射PDTC 120mg/kg后立即依HIR组方法致伤;对照组仅显露肝中叶及肝左叶肝蒂,不阻断,自阴茎背静脉注射无菌生理盐水1ml.分别采用原位杂交法、EMSA法、免疫组化及赖氏法检测再灌注后1、6、12h IκB激酶表达、NF-κB活性、TNF-α的表达及血浆中ALT含量.结果 损伤后IκB激酶表达增加,NF-κB结合活性明显升高,并于再灌注后6h达到高峰,肝组织TNF-α表达增强,血浆中ALT含量亦明显升高;HIR+ PDTC组与HIR组相比较,IκB激酶表达减弱,NF-κB活性降低,TNF-α表达减弱,血浆ALT水平降低.结论 HIR后肝内IκB激酶可促进NF-κB的高水平激活引起肝内TNF-α等炎症相关细胞因子表达增强,从而导致肝脏损伤.干预IKK-NF-κB通路可能是防止HIR后急性肝脏损伤发生发展的一个有效途径,PDTC对预防和治疗HIR后急性肝脏损伤有重要意义.
目的 探討IκB激酶在肝髒缺血再灌註(HIR)中的作用.方法 Wister大鼠隨機分為:對照組;缺血再灌註組(HIR組);PDTC保護組(HIR+ PDTC組).HIR組將肝左葉及肝中葉入肝血流阻斷60min後再灌註;保護組先經陰莖揹靜脈註射PDTC 120mg/kg後立即依HIR組方法緻傷;對照組僅顯露肝中葉及肝左葉肝蒂,不阻斷,自陰莖揹靜脈註射無菌生理鹽水1ml.分彆採用原位雜交法、EMSA法、免疫組化及賴氏法檢測再灌註後1、6、12h IκB激酶錶達、NF-κB活性、TNF-α的錶達及血漿中ALT含量.結果 損傷後IκB激酶錶達增加,NF-κB結閤活性明顯升高,併于再灌註後6h達到高峰,肝組織TNF-α錶達增彊,血漿中ALT含量亦明顯升高;HIR+ PDTC組與HIR組相比較,IκB激酶錶達減弱,NF-κB活性降低,TNF-α錶達減弱,血漿ALT水平降低.結論 HIR後肝內IκB激酶可促進NF-κB的高水平激活引起肝內TNF-α等炎癥相關細胞因子錶達增彊,從而導緻肝髒損傷.榦預IKK-NF-κB通路可能是防止HIR後急性肝髒損傷髮生髮展的一箇有效途徑,PDTC對預防和治療HIR後急性肝髒損傷有重要意義.
목적 탐토IκB격매재간장결혈재관주(HIR)중적작용.방법 Wister대서수궤분위:대조조;결혈재관주조(HIR조);PDTC보호조(HIR+ PDTC조).HIR조장간좌협급간중협입간혈류조단60min후재관주;보호조선경음경배정맥주사PDTC 120mg/kg후립즉의HIR조방법치상;대조조부현로간중협급간좌협간체,불조단,자음경배정맥주사무균생리염수1ml.분별채용원위잡교법、EMSA법、면역조화급뢰씨법검측재관주후1、6、12h IκB격매표체、NF-κB활성、TNF-α적표체급혈장중ALT함량.결과 손상후IκB격매표체증가,NF-κB결합활성명현승고,병우재관주후6h체도고봉,간조직TNF-α표체증강,혈장중ALT함량역명현승고;HIR+ PDTC조여HIR조상비교,IκB격매표체감약,NF-κB활성강저,TNF-α표체감약,혈장ALT수평강저.결론 HIR후간내IκB격매가촉진NF-κB적고수평격활인기간내TNF-α등염증상관세포인자표체증강,종이도치간장손상.간예IKK-NF-κB통로가능시방지HIR후급성간장손상발생발전적일개유효도경,PDTC대예방화치료HIR후급성간장손상유중요의의.
Objective To explore the effect of I kappa B kinase (IKK) on liver during hepatic ischemia reperfusion (HIR) in rats.Methods Wister rats were divided randomly into HIR group in which hepatic reperfusion was given after 60 minutes of ischemia by interruption of the arterial and portal venous blood supply to the left lobes and middle lobes of the liver; HIR + PDTC treatment group in which PDTC (120 mg/kg) were injected via the dorsum vein of penis before ischemia reperfusion; and sham control group in which midline laparotomy was performed without vascular occlusion and treatment.Expression levels of IKK were measured with In situ hybridization(ISH).The NF-κB activities were determined with EMSA.Expression levels of TNF-α were measured with immunohistochemistry (IH).Serum levels of ALT were measured.Results Expression level of IKK was increased markedly from 0 to 12h and peaked 6h after reperfusion in HIR group.NF-κB was activated 0 ～ 12h after reperfusion and activities of NF-κB were maximal 6h after reperfusion in HIR group rats compared with sham control group.Expression level of TNFα was increased markedly from 0 to 12h and peaked 6h after reperfusion in HIR group.Serum levels of ALT were increased significantly after reperfusion in H1R group.Expression level of IKK was lowered markedly in HIR + PDTC group from 0 to 12h after reperfusion.NF-κB activities were significantly lower in HIR +PDTC group than in HIR group from 0 to 12h after reperfusion.Expression level of TNF-α was lowered markedly in HIR + PDTC group as compared with HIR group from 0 to 12h after reperfusion.Serum level of ALT was decreased significantly after reperfusion in HIR + PDTC group as compared with HIR group.Conclusion HIR can activate IKK-β which promotes the activation of NF-κB,then NF-κB results in upregulation transcription of TNF-α gene which gives rise to the release of other inflammatory cytokines and triggers uncontrolled inflammatory response,and induces hepatic injury.Blocking IKK-NF-κB pathway may be an effective approach to checking the generation and development of ALI,PDTC plays important prophylaxis and treatment roles in hepatic injury after HIR.
