姜黄素对硫代乙酰胺诱导肝纤维化大鼠保护作用的研究

Protective Effect of Curcumin on Thioacetamide-induced Liver Fibrosis in Rats

目的探讨姜黄素对硫代乙酰胺(TAA)诱导肝纤维化大鼠的保护作用。方法健康成年SD大鼠50只随机分为正常组、模型组和姜黄素低、中、高剂量组,每组各10只,姜黄素组及模型组给予TAA溶液腹腔注射造模诱导肝纤维化模型,2次/周,连续8周,正常组给予等体积生理盐水注射。从第5周开始姜黄素低、中、高剂量组分别给予姜黄素溶液灌胃(100 mg/kg,200 mg/kg,400 mg/kg),模型组给予等体积的生理盐水灌胃,1次/d,共4周。实验结束后,生化法测定血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平;酶联免疫吸附试验(ELISA)测定血清中透明质酸(HA)、层黏连蛋白(LN)、Ⅲ型前胶原(PCⅢ)水平; Real time-PCR法检测结缔组织生长因子(CTGF)、α-平滑肌肌动蛋白(α-SMA) mRNA的表达;苏木精-伊红染色(HE)观察肝脏病理学改变。结果 HE切片显示模型组肝细胞排列紊乱,肝小叶结构破坏严重,可见变性、坏死的肝细胞,汇管区中心可见纤维组织增生。姜黄素各剂量组肝小叶结构破坏不同程度减轻,肝细胞结构排列较为整齐,纤维增生减少,肝损伤不同程度减轻;与正常组比较,模型组ALT、AST、HA、LN、PCⅢ水平升高(P<0. 05);与模型组比较,姜黄素各剂量组ALT、AST、HA、LN、PCⅢ水平明显下降(P<0.05);与正常组比较,模型组CTGF、α-SMA mRNA表达显著升高(P<0.01);与模型组比较,不同剂量姜黄素治疗组CTGF、α-SMA mRNA表达量下降(P<0. 05);结论姜黄素可缓解TAA诱导的大鼠肝纤维化,其机制可能与干预CTGF、α-SMA的表达有关。

Objective To investigate the protective effect of Curcumin on Thioacetamide( TAA)-induced liver fibrosis in rats.Methods 50 healthy adult SD rats were randomly divided into 5 groups: normal group,model group and 3 groups treated with low,medium and high doses of curcumin,10 rats in each group.The Curcumin group and model group were processed to be liver fibrosis model induced by intraperitoneal injection of TAA solution twice a week for 8 weeks.The normal group was given an equal volume of saline injection.From the 5 th week,the 3 groups with low,medium and high doses of Curcumin were given the corresponding doses of drug,and the model group was given an equal volume of normal saline,once a day for4 weeks.After treatment,the Alanine aminotransferase( ALT) and aspartate aminotransferase( AST) in serum was determined by biochemical assays.The hyaluronic acid( HA),adhesion protein( LN) and type Ⅲprocollagen( PCⅢ) in serum were determined by enzyme-linked immunosorbent assay( ELISA).The mRNA levels of CTGF( connective tissue growth factor),α-SMA( α-smooth muscle actin) were detected by Real time-PCR. Hematoxylin Staining( HE) was used to observe liver pathological changes. Results HE showed that the hepatocytes in the model group were disordered,and the structure of the hepatic lobule was severely damaged.Hepatocytes with degeneration and necrosis were seen,and fibrous tissue hyperplasia was observed in the center of the portal area.The structural damage of hepatic lobule in Curcumin groups was alleviated to a different extent.The structure of hepatocytes was neatly arranged,the fibrosis was reduced,and the liver damage was reduced to some extent.Compared with the normal group,the levels of ALT,AST,HA,LN and PCⅢ in the model group were higher( P<0.05 or 0.01).Compared with the model group,the levels of ALT,AST,HA,LN and PCⅢ in the Curcumin groups were significantly decreased( P < 0.05).Compared with the normal group,the expression of CTGF and α-SMA mRNA in the model group was significantly higher( P<0.01).Compared with the model group,the expression of CTGF and α-SMA mRNA in the Curcumin groups decreased( P<0.05).Conclusion Curcumin can relieve TAA-induced liver fibrosis in rats,which may be related with the interference of CTGFq and α-SMA’s expression.