枯否细胞NF-κB激活对胆源性内毒素血症大鼠肝部分切除后肝细胞再生的影响

Effect of NF-κB activation of Kupffer cells on liver regeneration after partial hepatectomy in rats with biliary endotoxemia

目的 探讨胆源性内毒素血症 (BE)大鼠肝部分切除 (PH)后枯否细胞 (KCs)核因子 κB(NF κB) )激活对肝细胞再生的影响。方法 将Wistar大鼠分为 4组 (每组 72只 ) :N PH组 (正常大鼠 70 %PH组 ) ;BE PH组 (BE大鼠 70 %PH组 ) ;BE PH白细胞介素 (IL) 1 0治疗组 ;BE PH治疗对照组。检测 70 %PH后 0、1、6、2 4、48、72hKCsNF κB激活、KCs肿瘤坏死因子α(TNFα)mRNA、IL 1 βmRNA和IL 6mRNA表达以及肝细胞溴脱氧核苷尿嘧啶 (BrdU)标记。 结果 BE PH组KCsNF κB活性高于N PH组 (P <0 .0 0 1 ) ,KCsTNFαmRNA、IL 1 βmRNA及IL 6mR NA表达亦明显高于N PH组 ,而肝细胞BrdU高峰标记指数 (38.82± 9.79)低于N PH组 (64.37±1 3 .69) (P <0 .0 1 ) ;BE PHIL 1 0组KCsNF κB活性低于BE PH组 (P <0 .0 1 ) ,KCsTNFα、IL 1 β及IL 6mRNA表达减少 ,而肝细胞BrdU高峰标记指数高于BE PH组 (P <0 .0 5)。结论 BE PH后KCsNF κB高水平激活导致KCsTNFαmRNA、IL 1 βmRNA及IL 6mRNA表达增高 ,从而抑制肝细胞再生 ,适当调控KCsNF κB活性能促进BE PH后肝细胞再生。

Objective To investigate the effect of nuclear factor kappa B (NF κB ) activation of Kupffer cells (KCs) on liver regeneration after 70% partial hepatectomy (PH) in rats with biliary endotoxemia (BE).Methods Wistar rats were randomly divided into 4 groups (72 rats each):N PH group,normal rats receiving 70% PH;BE PH group,BE rats receiving 70% PH;BE PH interleukin (IL) 10 treatment group;BE PH sterile saline treatment group.NF κB activation of KCs was measured by electrophoretic mobility shift assay (EMSA).Expression of TNFα mRNA,IL 1β mRNA and IL 6 mRNA of KCs was detected by using reverse transcription polymerase chain reaction (RT PCR).Bromodeoxyuridine (BrdU) labelling of hepatocytes was investigated by immunohistochemical analysis.Results NF κB of KCs was activated from 0 to 72?h after 70% PH in the rats of BE PH group,and their activities were significantly higher than those in the rats of N PH group (P<0.001).Expression of TNFα?mRNA,IL 1β?mRNA and IL 6 mRNA of KCs after 70% PH in the rats of BE PH group was increased significantly as compared with that in the N PH group.The peak levels of BrdU labelling of hepatocytes (38.82± 9.79) in the BE PH were significantly lower than that (64.37±13.69) in the N PH group (P< 0.01); NF κB activities of KCs were markedly lower in BE PH IL 10 treatment group than those in the BE PH group at 0,1,6,24,48,72?h afte 70% PH (P<0.01).Eexpression levels of TNFα?mRNA,IL 1β?mRNA and IL 6 mRNA of KCs were decreased markedly and the peak BrdU labelling of hepatocytes were increased significantly in BE PH IL 10 treatment group as compared with BE PH group.Conclusion The excessive NF κB activation of KCs after 70% PH inhibited proliferation of hepatocytes by elevating KCs mRNA expression of TNFα,IL 1β and IL 6 in rats with BE,and adjustment of KCs NF κB activity to a appropriate level could promote liver regeneration after BE PH.