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目的探讨芦荟大黄素对血吸虫肝纤维化小鼠的疗效及可能的作用机制。方法采用日本血吸虫尾蚴感染小鼠建立血吸虫性肝纤维化模型,用芦荟大黄素0.3mg/kg.d-1灌胃治疗8周。免疫组化检测肝组织转化生长因子β1(TGF-β1)、血小板源性生长因子(PDGF)、Ⅰ型胶原和Ⅲ型胶原的表达。RT-PCR检测细胞周期蛋白依赖性激酶4(CDK4)mRNA和细胞周期蛋白D1(cyclinD1)mRNA。结果实验对照组小鼠肝脏TGF-β1、PDGF、I型胶原和Ⅲ型胶原的平均吸光度值分别为0.2775±0.0810、0.2140±0.0069、0.2234±0.0248和0.1849±0.0231,较正常对照组升高(P<0.01)。CDK4和cyclinD1基因表达增加。芦荟大黄素干预后,小鼠肝脏TGF-β1、PDGF、Ⅰ型胶原和Ⅲ型胶原的平均吸光度值分别为0.1615±0.0326、0.1324±0.0201、0.1652±0.0216和0.1409±0.0206,较实验对照组降低(P<0.01)。CDK4和cyclinD1基因表达受到抑制。结论芦荟大黄素对血吸虫性肝纤维化有治疗作用,其作用机制可能与影响肝星状细胞周期有关。
Objective To investigate the therapeutic effect and possible mechanism of aloe-emodin on schistosome-induced liver fibrosis in mice. Methods Schistosoma japonicum cercariae infected mice were used to establish schistosomiasis model of hepatic fibrosis and treated with aloe-emodin 0.3mg / kg.d-1 for 8 weeks. Immunohistochemistry was used to detect the expression of transforming growth factor β1 (TGF-β1), platelet-derived growth factor (PDGF), type Ⅰ collagen and type Ⅲ collagen. RT-PCR was used to detect the expression of cyclin-dependent kinase 4 (CDK4) mRNA and cyclin D1 mRNA. Results The mean absorbance values of TGF-β1, PDGF, type I collagen and type Ⅲ collagen in experimental control group were 0.2775 ± 0.0810,0.2140 ± 0.0069,0.2234 ± 0.0248 and 0.1849 ± 0.0231, respectively, which were significantly higher than those in normal control group (P <0.01). CDK4 and cyclinD1 gene expression increased. After the intervention of aloe-emodin, the average absorbance values of TGF-β1, PDGF, collagen type Ⅰ and type Ⅲ collagen in mouse liver were 0.1615 ± 0.0326,0.1324 ± 0.0201,0.1652 ± 0.0216 and 0.1409 ± 0.0206 respectively, which were lower than those in the experimental control group P <0.01). CDK4 and cyclinD1 gene expression was inhibited. Conclusion Aloe-emodin has a therapeutic effect on schistosome-induced hepatic fibrosis, and its mechanism may be related to the influence of hepatic stellate cell cycle.