摘要
目的探讨Kupffer细胞(KCs)NF-kB激活在缺血再灌注肝损伤中的作用。方法 Wistar大鼠随机分为肝缺血再灌注(HIR)组、HIR IL-10治疗组、HIR生理盐水治疗组及对照组。HIR组大鼠肝左叶及中肝叶缺血90min后再灌注,治疗组分别于肝缺血前及再灌注前从阴茎背静脉注入重组鼠IL-10(10mg/kg)或生理盐水,对照组仅显露肝门部血管但不进行缺血再灌注与治疗。分别采用EMSA法及RT-PCR法检测再灌注后0h、1h、3h、6h及12h KCsNF-kB活性和KCs TNF-αmRNA、IL-6mRNA、IL-1βmRNA表达,检测HIR后0h与12h血清ALT及AST水平。结果 HIR后0h～12h KCs NF-kB明显激活并于HIR后3h达到高峰;HIR后0h～12h KCs TNFαmRNA、IL-6mRNA及IL-1βmRNA表达显著高于对照组,并于HIR后3h达到高峰;HIR后0h与12h血ALT及AST活性明显高于对照组.IL-10治疗能显著降低HIR后KCs NF-kB活性及减少KCs源性TNFαmRNA、IL-1βmRNA与IL-6mRNA表达,从而缓解HIR后肝损伤。结论 HIR后KCs NF-kB高水平激活并促进KCs源性肝细胞损害递质的表达从而促进肝损害。
AIM To explore the effect of Kupffer cells (KCs) NF-kB activation on liver injury during hepatic ischemia/ reperfusion(HIR) in rats. METHODS Wistar rats were divided randomly into HIR group in which hepatic reperfusion was given after 90 minutes of ischemia by interruption of the arterial and portal venous blood supply to the left lobes and middle lobes of the liver; HIR IL-10/saline treatment group in which recombinant murine IL-10 (10mg/kg) or normal saline were injected via the dorsum vein of penis before ischemia and reperfusion; and sham control group in which midline laparotomy was performed without vascular occlusion and treatment. NF-kB activities of KCs were determined with EMSA. Expression levels of TNFαmRNA, IL-6mRNA and IL-1βmRNA of KCs were measured with RT- PCR. Serum levels of ALT and AST were measured. RESULTS KCs NF-kB were activated 0-12h after reperfusion and activities of NF-kB were maximal 3h after reperfusion in HIR group. Expression levels of TNFαmRNA, IL-6 mRNA and IL-1βmRNA of KCs were increased markedly from 0 to 12h and peaked 3h after reperfusion in HIR group, and the mRNA expression levels of KCs were significantly higher in HIR group than in sham control group. Serum levels of ALT and AST were increased significantly after reperfusion in HIR group rats compared with sham control group; KCs NF-kB activities were significantly lower in HIR IL-1O treatment group than in HIR group from 0 to 12h after reperfusion. Expression levels of TNFαmRNA, IL-6 mRNA and IL-1βmRNA of KCs were lowered markedly in HIR IL-10 treatment group as compared with HIR group from 0 to 12h after reperfusion. Serum levels of ALT and AST were decreased significantly after reperfusion in HIR IL-10 treatment group as compared with HIR group. CONCLUSIONS NF-kB activation of KCs after HIR induces hepatic injury by promoting expressions of TNFαmRNA, IL-6mRNA and IL-1βmRNA of KCs. IL-10 protects against hepatic injury by suppressing excessive NF-kB activation of KCs and the subsequent mRNA expressions of proinfia
出处
《世界华人消化杂志》
CAS
2001年第11期1250-1253,共4页
World Chinese Journal of Digestology
关键词
肝
病理学
再灌注损伤
代谢
病理生理学
枯否氏细胞
NF-KB
Liver / pathology
Reperfusion injury / metabolism
Reperfusion injury / physiopathology
Kupffer cells / metabelism
NF-kB / metaboism
