作　　者： (许妍妍）;

机构地区： 南京市中医院科教科

出　　处： 《世界临床药物》 2017年第8期522-527,共6页

摘　　要： 目的探索二氢杨梅素对四氯化碳(CCl_4)致肝纤维化大鼠的防护作用及其机制,为临床肝纤维化的治疗提供新策略。方法清洁级雄性SD大鼠,随机分为空白对照组,模型组,二氢杨梅素高、中、低剂量组(500、250、125 mg/kg),每组各10只,连续给药8周后处死,以苏木精-伊红(HE)染色观察肝组织病理学改变,Masson染色及天狼星红染色观察胶原纤维沉积情况,组织免疫荧光染色分析肝组织中α-平滑肌肌动蛋白(α-SMA)与核因子-κB(NF-κB)p65的表达,采用蛋白质印迹法与实时聚合酶链反应(PCR)检测肝纤维化标志物、炎症及凋亡相关通路蛋白与基因的表达情况。结果二氢杨梅素能显著改善CCl_4所致肝组织病理学改变。模型组大鼠α-SMA、纤维连接蛋白及NF-κB p65呈现高表达状态,与模型组相比,二氢杨梅素高、中及低剂量组上述指标表达均降低(P<0.05或P<0.01),且呈剂量依赖关系。模型组、二氢杨梅素低、中及高剂量组caspase-3蛋白表达水平依次升高。α-SMA、纤维连接蛋白、NF-κB p65及caspase-3的m RNA表达与蛋白表达情况相同。结论二氢杨梅素具有显著的抗肝纤维化效应,且呈现剂量依赖关系,可能与其干扰肝细胞NF-κB通路及促进肝星状细胞凋亡、抑制细胞外基质生成有关。 Objective To explore the protective effect and the mechanism of dihydromyricetin on the rat liver fibrosis induced by carbon tetrachloride(CCl_4) and to provide a new treatment strategy for liver fibrosis in clinical. MethodsThe cleaning laboratory male SD rats were randomly divided into blank control group, model group(treated by CCl_4), dihydromyricetin high, medium and low dose(500, 250, 125 mg/kg for post CCl_4 treated rat) groups. After 8 week continuous dosing, the rats were put to death were prepared. The HE staining was used to observe pathological change. The Masson staining and the sirius red staining were used to observe the collagen deposition. The α-SMA and NF-κB p65 in liver tissue were visualized by immunofluorescence staining. The protein and gene expressions of liver fibrosis markers, inflammation and apoptosis related pathway were analyzed by Western blot and real time-PCR. Results Dihydromyricetin could significantly improve the liver tissue pathological change caused by CCl_4. The α-SMA, fibronectin and NF-κB p65 of rats in model group showed high expression status. The dihydromyricetin high, medium and low dose group showed a decrease in dose-dependent manner compared with the model group(P<0.05 or 0.01). The expressions of caspase-3 were increased successively in model group and the dihydromyricetin low, medium and high dose group. The expressions of m RNA of α-SMA, fibronectin, NF-κB p65 and caspase-3 were same as those of protein. Conclusion Dihydromyricetin has significant anti-fibrosis effect. The effect may be due to the interference with the NF-κB pathway in liver. It may promote hepatic stellate cell apoptosis and inhibit the generation of extracellular matrix.

关 键 词： 二氢杨梅素 肝纤维化 炎症 凋亡 细胞外基质