姜黄素治疗肝纤维化及其作用机制的初步研究

Therapeutic effects of curcumin treatment on hepatic fibrosis

目的观察姜黄素治疗肝纤维化的效果,初步探讨其作用机制。方法四氯化碳腹腔注射制作大鼠肝纤维化模型,以丹参治疗作为阳性对照,检测血清ALT、AST、HA、LN、Ⅲ型前胶原（PCⅢ）、一氧化氮（NO）含量;检测肝组织超氧化物歧化酶（SOD）、羟脯氨酸（Hyp）、丙二醛（MDA）含量;肝组织行HE和Masson胶原染色,光镜下观察病理学改变,并按肝纤维化半定量计分系统进行评分。结果与模型组比较,姜黄素治疗组能明显降低肝纤维化时异常升高的ALT、AST、NO、HA、LN、PCⅢ、MDA、Hyp,模型对照组分别为（693.75±117.57）U/L、（892.50±105.69）U/L、（70.95±10.23）μmol/L、（468.22±93.45）mg/L、（346.44±75.08）mg/L、（279.82±54.00）μg/L、（402.25±39.16）nmol/g、（752.50±77.62）μg/g,姜黄素（每100g体重40mg）治疗组分别为（218.50±48.89）U/L、（376.60±79.13）U/L、（47.96±6.53）μmol/L、（289.96±60.43）mg/L、（107.35±27.24）mg/L、（148.95±28.63）μg/L、（236.10±30.54）nmol/g、（478.40±75.74）μg/g,P值均〈0.05;提升肝纤维化时异常降低的肝组织SOD水平,姜黄素（每100g体重40 mg）治疗组和对照组分别为（90.39±21.23）U/mg、（46.52±20.01）U/mg,P〈0.05;明显改善四氯化碳所致大鼠肝纤维化的病理学改变,肝纤维化评分明显降低（P〈0.05）,接近正常对照组,且该作用随着姜黄素剂量增大而加强。结论姜黄素具有治疗大鼠肝纤维化作用;抗脂质过氧化损伤、直接影响胶原代谢可能是其重要的作用机制。

Objective To investigate the therapeutic effects and mechanisms of curcumin treatment on hepatic fibrosis. Methods A model of hepatic fibrosis was established using carbon tetrachloride intraperitoneal injections in rats. Curcumin was administered to one group of the model rats （curcumin group） and the other rats were used as controls （control group）. Serum levels of ALT, AST, HA, LN, PCIII, and NO were measured, and Hyp, MDA, and SOD in liver tissues were measured. Liver tissue slides were stained with HE and Masson staining to study the pathological changes in the livers. Grades of hepatic fibrosis were evaluated according to a semiquantitative scoring system. Results In the curcumin group, serum levels of ALT, AST, NO, HA, LN, PCIH, MDA, and Hyp, were （218.50 ± 48.89） U/L, （376.60 ± 79.13） U/L, （47.96 ± 6.53） lamol/L, （289.96 ± 60.43） mg/L, （107.35 ± 27.24） mg/L, （148.95 ± 28.63） μg/L, （236.10 ± 30.54） nmol/g, （478.40 ± 75.74） μg/g and all were lower than those of the control group （693.75 ± 117.57） U/L, （892.50 ± 105.69） U/L, （70.95 ± 10.23） μmol/L, （468.22 ± 93.45） mg/L, （346.44 ± 75.08） rag/L, （279.82 ± 54.00） μg/L, （402.25 ± 39.16） nmol/g, and （752.50 ± 77.62） μg/g. The differences were significant （P 〈0.01）. In the curcumin group, the level of SOD （90.39 ± 21.23） in the liver tissues was significantly higher （P 〈0.01） than that of the control group （46.52 ± 20.01）. The hepatic fibrosis scores in the curcumin group were significantly lower than those of the control group, （P 〈0.01）. These effects were dose-dependent. Conclusion Curcumin reduces rat hepatic fibrosis. Anti-peroxidation and regulation of collagen metabolism in liver tissues may be involved in the therapeutic effectiveness of curcumin on hepatic fibrosis.