Ji Guang, Wang Lei, Zhang Shui-Hua, Liu Jian-Wen, Zheng Pei-Yong, Liu Tao
Laboratory of Liver Disease, Long Hua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
World J Gastroenterol. 2006 Apr 7;12(13):2047-52. doi: 10.3748/wjg.v12.i13.2047.
To investigate the effect of Qinggan Huoxuefang (QGHXF) on improvement of liver function and pathology in rats, and to analyze the mechanism.
Wistar rats were divided into three groups at random: normal control group (12),micro-amount carbon tetrachloride group (CCl(4))(12) and model group A (60). The model group A was ingested with the mixture (500 mL/L alcohol, 8 mL/kg per day; corn oil, 2 mL/kg per day; pyrazole, 24 mg/kg per day) once a day and intraperitoneal injections of 0.25 mL/kg of a 250 mL/L solution of CCl(4) in olive oil twice a week for 12 wk. The CCl(4) group received intraperitoneal injections only. At the end of 8 wk the model group A (60) was divided into 5 subgroups: model group, Xiaochaihu Chongji (XCH) group, QGHXF high dose group, moderate dose group and low dose group, and were given the drugs respectively. At the end of 12 wk, all the rats were killed and blood samples collected, as well as liver tissue. Blood samples were used for evaluation of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (gamma-GT). Liver specimens were obtained for routine HE, apoptosis gene array and flow cytometry analysis.
A liver fibrosis animal model was successfully established. Fibrosis was obviously reduced in QGHXF high dose group, and no fibrosis formed in CCl(4) group. Compared with model group the QGHXF group and XCH group could obviously decrease the level of ALT, AST, ALP, and GGT (P<0.05). QGHXF high dose group was better than XCH group in ALT (615+/-190 vs 867+/-115), and AST(1,972+/-366 vs 2,777+/-608). Moreover, QGHXF could reduce liver inflammation, fibrosis-induced hepatic stellate cell (HSC) apoptosis and regulate apoptosis gene expression. The HSC apoptosis rates of QGHXF groups were 22.4+/-3.13, 13.79+/-2.26 and 10.07+/-1.14, higher than model group, 6.58+/-1.04 (P<0.05). Compared to model group, 39 genes were up-regulated, 11 solely expressed and 17 down-regulated in high dose group.
QGHXF can improve liver fibrosis and induce HSC apoptosis.
探讨清肝活血方（QGHXF）对大鼠肝功能及肝脏病理的改善作用，并分析其作用机制。
将Wistar大鼠随机分为三组：正常对照组（12只）、微量四氯化碳组（CCl₄）（12只）和模型A组（60只）。模型A组大鼠每日灌胃给予混合液（500 mL/L乙醇，8 mL/kg；玉米油，2 mL/kg；吡唑，24 mg/kg），每周两次腹腔注射0.25 mL/kg的250 mL/L四氯化碳橄榄油溶液，持续12周。CCl₄组仅进行腹腔注射。8周结束时，将模型A组（60只）分为5个亚组：模型组、小柴胡冲剂（XCH）组、清肝活血方高剂量组、中剂量组和低剂量组，分别给予相应药物。12周结束时，处死所有大鼠，采集血液样本及肝脏组织。血液样本用于检测丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）、γ-谷氨酰转肽酶（γ-GT）。获取肝脏标本进行常规HE染色、凋亡基因芯片及流式细胞术分析。
成功建立肝纤维化动物模型。清肝活血方高剂量组纤维化明显减轻，CCl₄组未形成纤维化。与模型组相比，清肝活血方组和小柴胡冲剂组可明显降低ALT、AST、ALP及GGT水平（P<0.05）。清肝活血方高剂量组在ALT（615±190 vs 867±115）和AST（1972±366 vs 2777±608）方面优于小柴胡冲剂组。此外，清肝活血方可减轻肝脏炎症，诱导肝星状细胞（HSC）凋亡并调节凋亡基因表达。清肝活血方各剂量组的HSC凋亡率分别为22.4±3.13、13.79±2.26和10.07±1.14，高于模型组的6.58±1.04（P<0.05）。与模型组相比，高剂量组有39个基因上调，11个基因单独表达，17个基因下调。
清肝活血方可改善肝纤维化并诱导HSC凋亡。
