退黄合剂对ANIT致胆汁淤积性肝损伤的保护作用及机制研究

目的 观察退黄合剂对异硫氰酸-1-萘酯（ANIT）诱导的胆汁淤积性肝损伤的保护作用.方法 SD大鼠随机分成5组,即空白对照组,ANIT模型组,退黄合剂低、中、高剂量组,大鼠在ANIT处理48 h后被处死,检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）活性及总胆红素（TBIL）和直接胆红素（DBIL）含量;肝组织做组织切片HE染色;分析肝组织中SOD和MPO活性;酶联免疫法分析肝组织中巨噬细胞炎性蛋白（MIP）-2生成;免疫印迹法检测细胞间黏附分子（ICAM）-1表达.结果 与空白对照组相比,模型组ALT、AST、ALP、DBIL、TBIL、MPO和MIP-2显著增高（P＜0.01）,肝脏病理病变明显,肝组织Ⅰ-CAM-1表达上调;与模型组相比,退黄合剂呈剂量依赖地降低ALT、AST、ALP、DBIL、TBIL、MPO和MIP-2,减轻肝脏病变,下调ICAM-1的表达（P＜0.05或P＜0.01）.结论 退黄合剂能保护ANIT诱导的胆汁淤积性肝损伤,其作用机制可能与抑制MIP-2和ICAM-1,减少中性粒细胞浸润,减轻炎症性肝脏损伤有关.

Protective Effect and Mechanism of Tuihuang Injection on ANIT induced Cholestatic Liver Injury

Objective： To observe the effect and mechanism of Tuihuang Injection on ANIT induced cholestatic liver injury. Methods： SD rats were randomly divided into the normal saline control group,the ANIT model group,the Tuihuang Injection low-dose,middle-dose and high-dose＋ANIT groups. 48h after ANIT administra- tion,serum were collected to detect ALT, AST, ALP, DBIL and TBIL. MPO and SOD activities in hepatic tissues were measured,and MIP-2 and ICAM-1 expressions were determined by ELISA and Western bloting. Results： Compared with control group, there were significant increases in serum ALT, AST, ALP, DBIL and TBIL as well as hepatic MPO activity,MIP-2 and ICAM-1 in the ANIT model group （P〈 0.01）. However,compared with ANIT model group, Tuihuang Injection dose-dependently inhibited ANIT-induced ALT,AST,ALP,DBIL and TBIL in serum. MPO,MIP-2 and ICAM-1 expressions were also suppressed by Tuihuang Injection in a dose-dependent manner. Conclusion： Tuihuang Injection has protective effect on ANIT-induced cholestatic liver injury probably by inhibiting MIP-2 and ICAM-1 ,blocking neutrophils invasion,and alleviating inflammatory liver injury.