Mu Yongping, Liu Ping, Du Guangli, Du Jinxing, Wang Gaoqiang, Long Aihua, Wang Lei, Li Fenghua
Institute of Liver Diseases, Shuangguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
J Ethnopharmacol. 2009 Jan 12;121(1):35-42. doi: 10.1016/j.jep.2008.09.032. Epub 2008 Oct 18.
To investigate action mechanism of Yi Guan Jian Decoction on cirrhosis induced by CCl(4) in rats.
CCl(4) (3 mL/kg) for the first time and then olive oil CCl(4) solution 50% (2 mL/kg) was administered hypodermically to rats twice each week for 12 weeks. At the end of 8th week, rats were randomly divided into CCl(4) control group (n=10), Yi Guan Jian Decoction group (n=9) and Xiao Chai Hu Decoction group (n=9). Yi Guan Jian Decoction and Xiao Chai Hu Decoction were oral administrated per day respectively for 4 weeks, concomitantly continued CCl(4) administration. At 12th weekend, the rats were sacrificed for sampling and detection of liver function, histological changes of liver tissue, liver tissue hydroxyproline content and expression of alpha-SMA, CD68, MMP-13, TIMP-1, TIMP-2, Caspase-12, HGFalpha, MMP-2, MMP-9 and hepatocyte apoptotic index.
(1) Compared with that of normal rats, expression of alpha-SMA, CD68 and TIMP-1 in liver tissue of 8 week model group rats increases significantly (P<0.01), moreover further increased in the 12 week of model group. However, MMP-13, HGFalpha, TIMP-2 content decreases gradually and the statistical difference is seen between each time point (P<0.01). Activity of MMP-2, MMP-9, content of Caspase-12 and hepatocyte apoptotic index increased gradually at 4th, 8th, 12th week. (2) Compared to that of the same time point model group, activity of MMP-9 and contents of MMP-13, TIMP-2 and HGFalpha in Yi Guan Jian Decoction group improves significantly (P<0.01), and activity of MMP-2 and contents of alpha-SMA, TIMP-1, Caspase-12 and hepatocyte apoptotic index decreases significantly (P<0.01). This work suggests that Yi Guan Jian Decoction exerts significant therapeutic effect on CCl(4)-induced cirrhosis in rats, through mechanism of inhibiting hepatocytes apoptosis and hepatic stellate cells activation, and regulating the function of Kupffer cell.
This study investigates the mechanism of Yi Guan Jian against cirrhosis from aspect of heptocytes apoptosis and hepatic stellate cells activation. It suggest that although of unknown bioactive ingredients, mechanism of traditional Chinese medicine recipe against cirrhosis can be disclosed and of profound significance.
探讨一贯煎对四氯化碳诱导的大鼠肝硬化的作用机制。
首次皮下注射四氯化碳（3 mL/kg），然后每周两次皮下注射50%四氯化碳橄榄油溶液（2 mL/kg），共12周。在第8周结束时，将大鼠随机分为四氯化碳对照组（n = 10）、一贯煎组（n = 9）和小柴胡汤组（n = 9）。一贯煎和小柴胡汤分别每日灌胃给药4周，同时继续给予四氯化碳。在第12周末，处死大鼠进行取样，检测肝功能、肝组织组织学变化、肝组织羟脯氨酸含量以及α-SMA、CD68、MMP-13、TIMP-1、TIMP-2、Caspase-12、HGFα、MMP-2、MMP-9的表达和肝细胞凋亡指数。
（1）与正常大鼠相比，8周模型组大鼠肝组织中α-SMA、CD68和TIMP-1的表达显著增加（P < 0.01），且在模型组12周时进一步增加。然而，MMP-13、HGFα、TIMP-2含量逐渐降低，各时间点之间存在统计学差异（P < 0.01）。MMP-2、MMP-9活性、Caspase-12含量和肝细胞凋亡指数在第4、8、12周逐渐升高。（2）与同时间点模型组相比，一贯煎组MMP-9活性以及MMP-13、TIMP-2和HGFα含量显著改善（P < 0.01），MMP-2活性以及α-SMA、TIMP-1、Caspase-12含量和肝细胞凋亡指数显著降低（P < 0.01）。本研究表明，一贯煎对四氯化碳诱导的大鼠肝硬化具有显著治疗作用，其机制可能是通过抑制肝细胞凋亡和肝星状细胞活化，以及调节库普弗细胞功能。
本研究从肝细胞凋亡和肝星状细胞活化方面探讨了一贯煎抗肝硬化的机制。这表明，尽管中药复方的生物活性成分尚不清楚，但仍可揭示其抗肝硬化的机制，具有重要意义。
