氧化苦参碱对实验性肝纤维化的体内作用及其机制
Effects of oxymatrine on experimental hepatic fibrosis and its mechanism in vivo.
作者信息
Shi Guang-Feng, Li Qian
机构信息
Department of Infectious Diseases, Hua Shan Hospital, Fu Dan University, Shanghai 200040, China.
出版信息
World J Gastroenterol. 2005 Jan 14;11(2):268-71. doi: 10.3748/wjg.v11.i2.268.
AIM
Hepatic fibrogenesis has close relation with hepatic stellate cells (HSC) and tissue inhibitors of metalloproteinase (TIMP). Oxymatrine (OM) is a kind of Chinese herb that is found to have some effects on liver fibrosis. We aimed to determine the effects of OM on hepatic fibrosis and explore the possible mechanism.
METHODS
Thirty-two rats were randomly divided into four groups; 16 were used to develop hepatic fibrosis by carbon tetrachloride (CCl4) and treated with or without OM, and 16 were used as controls. The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and alpha-smooth muscle actin (alpha-SMA) in the livers of rats was detected by immunohistochemical assay. Liver pathology was determined by H and E staining and reticulum staining.
RESULTS
In CCl4-injured rats, the normal structure of lobules was destroyed, and pseudolobules were formed. Hyperplasia of fibers was observed surrounding the lobules. While the degree of fibrogenesis in liver tissues was significantly decreased in those rats with OM-treatment compared with those without OM treatment. The pseudolobules were surrounded by strong, multi-layer reticular fibers, which netted into pseudolobules in CCl4-injured rats, however, there was a significant decrease in reticular fibers in OM-treated rats. The expression of TIMP-1 in hepatic cells was weak in control groups, but strong in CCl4-injured groups, however, the expression of TIMP-1 was significantly inhibited by OM (F = 52.93, P<0.05). There was no significant change in the expression of alpha-SMA between CCl4-injured rats with or without OM treatment (F = 8.99, P>0.05).
CONCLUSION
OM effectively inhibits CCl4-induced fibrogenesis in rat liver tissues, probably by reducing the expression level of TIMP-1.
目的
肝纤维化的发生与肝星状细胞（HSC）及基质金属蛋白酶组织抑制剂（TIMP）密切相关。氧化苦参碱（OM）是一种被发现对肝纤维化有一定作用的中药。我们旨在确定OM对肝纤维化的影响并探讨其可能的机制。
方法
32只大鼠随机分为四组；16只通过四氯化碳（CCl4）诱导肝纤维化，并分别给予或不给予OM治疗，另外16只作为对照。采用免疫组织化学法检测大鼠肝脏中基质金属蛋白酶组织抑制剂-1（TIMP-1）和α-平滑肌肌动蛋白（α-SMA）的表达。通过苏木精-伊红（H&E）染色和网状纤维染色确定肝脏病理情况。
结果
在CCl4损伤的大鼠中，小叶正常结构被破坏，假小叶形成。在小叶周围观察到纤维增生。与未接受OM治疗的大鼠相比，接受OM治疗的大鼠肝组织纤维化程度明显降低。在CCl4损伤的大鼠中，假小叶被粗大的多层网状纤维围绕，这些纤维交织形成假小叶，然而，在接受OM治疗的大鼠中网状纤维明显减少。对照组肝细胞中TIMP-1表达较弱，而在CCl4损伤组中表达较强，然而，OM可显著抑制TIMP-1的表达（F = 52.93，P<0.05）。接受或未接受OM治疗的CCl4损伤大鼠之间α-SMA的表达无显著变化（F = 8.99，P>0.05）。
结论
OM可有效抑制CCl4诱导的大鼠肝组织纤维化，可能是通过降低TIMP-1的表达水平实现的。
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