阻塞性黄疸大鼠肝脏NF-κB对炎性介质表达的调控及其在肝损伤中的作用

Regulation of Nuclear Factor-kappa B on Expression of Inflammatory Media in Liver and Its Role in Liver Injury in Rats with Obstructive Jaundice

目的探讨阻塞性黄疸(obstructive jaund ice,OJ)时核因子κB(nuc lear factor kappa B,NF-κB)对炎性介质的调控及其在肝损伤中的作用。方法应用大鼠OJ模型,观察OJ 4、7、14 d及腹腔注射NF-κB抑制剂脯氨酸二硫化氨基甲酸酯(pyrrolid ined ith iocarbam ate,PDTC)后肝组织NF-κB P65蛋白表达、肿瘤坏死因子-α(TNF-α)mRNA、白介素-6(IL-6)mRNA、细胞间黏附分子-1(ICAM-1)mRNA表达以及血清总胆红素(total b ilirub in,TB)、谷丙转氨酶(ala-n ine transm inase,ALT)水平。结果OJ 4、7、14 d大鼠出现明显的肝损伤,表现为TB、ALT的明显增高,肝组织NF-κB P65表达明显增加,TNF-α、IL-6mRNA、ICAM-1mRNA表达也增强。注射PDTC的OJ大鼠肝NF-κB P65、ICAM-1mRNA表达较OJ各时相点显著下降,血清ALT和肝组织TNF-αmRNA较OJ在4、7 d明显下降。结论OJ时NF-κB的活化上调了炎性介质的表达,从而造成肝损伤,通过PDTC抑制NF-κB活化可减轻病程早期的肝脏损伤。

Objective To investigate the regulation of nuclear factor-kappa B（NF-κB） on expression of inflammatory media in the liver and its role in liver injury in rats with obstructive jaundice（OJ）. Methods By using the model of OJ in rats, serum alanine transrninase（ALT）, hepatic NF-κB activities and the expression of TNF-α mRNA, IL-6 mRNA, ICAM-1mRNA were examined with peritoneal injection of either prolien dithiocarbamates（PDTC） or sterile saline. Results 4, 7 or 14 days after OJ, the hepatic injury appeared with the elevations of serum ALT and total bilirubin（TB）. The level of hepatic NF-κB P65 obviously elevated with the prolongation of OJ. The transcription of TNF-α, IL-6 and ICAM- 1 significantly increased on 4, 7 and 14 days after OJ. PDTC treatment significantly decreased the content of NF-κB P65 in the liver in concurrence with the expression of ICAM-1. The level of serum ALT and hepatic expression of TNF- α mRNA decreased 4 or 7 d after administration of PDTC. Conclusion The activation of hepatic NF-κB is associated with the liver injury by regulating expression of proinflammatory mediators and PDTC protects the liver from early inflammatory injury in obstructive jaundice.