姜黄素mPEG-PLGA纳米粒逆转二甲基亚硝胺大鼠肝纤维化作用研究

Action of Curcumin Nanoparticle Preparation mPEG-PLGA on Reversing Liver Fibrosis in Rats Induced by Dimethylnitrosamine

目的:观察姜黄素mPEG-PLGA纳米粒逆转大鼠肝纤维化作用。方法:用溶剂挥发法制备聚乙二醇聚乳酸乙酸酯(mPEG-PLGA)载姜黄素纳米粒,大鼠腹腔内注射0.5%DMN(2mL.kg-1),每周连续3天,每天1次,共4周造肝纤维化模型。大鼠随机分为对照组、模型组和药物治疗组,药物治疗组又分为姜黄素组、姜黄素纳米粒低剂量组和姜黄素纳米粒高剂量组,每组12只。模型组及对照组给予等量生理盐水:给药方式为腹腔注射,姜黄素组为每日姜黄素50mg.kg-1,姜黄素纳米粒低剂量组和姜黄素纳米粒高剂量组分别为每日姜黄素10mg.kg-1和30mg.kg-1。用药治疗4周后杀鼠取材料。全部实验大鼠采血,取肝组织,分别检测血清ALT活性、AST活性、检测肝组织Hyp含量、MDA活性、SOD活性、GSH-PX活性、GST活性,观察肝组织胶原沉积变化。结果:①与正常组比较,模型组大鼠血清ALT活性、AST活性显著升高(P﹤0.05);与模型组比较,治疗组大鼠血清ALT活性、AST活性显著降低。②与正常组比较,模型大鼠肝组织Hyp含量显著升高(P﹤0.05);与模型组比较,药物治疗组大鼠肝组织Hyp含量显著降低(P﹤0.05)。③模型组大鼠肝组织可见炎性细胞浸润,胶原增生明显,大多数形成较厚的完全间隔。药物治疗组有所改善。④与正常组大鼠相比较,模型组大鼠肝组织总SOD、GSH-PX活性显著降低(P﹤0.01),肝组织MDA、GST活性显著升高(P﹤0.01);药物治疗组的SOD、GSH-PX活性显著升高,MDA含量、GST活性显著降低(P﹤0.01)。结论姜黄素mPEG-PLGA纳米粒能够逆转大鼠肝纤维化,显著改善肝功能,能够显著减轻过氧化损伤,保护肝细胞,减少胶原生成,阻断和逆转二甲基亚硝胺大鼠肝纤维化。

Objective：To investigate the effect of curcumin nanoparticle preparation mPEG-PLGA on reversing liver fibrosis in rats.Methods：The solvent evaporation method was used to prepare mPEG-PLGA nanoparticles containing curcumin.From the 1st to 4th week,rats were treated with intraperitoneal injection of 0.5% DMN（2mL/kg） for three continuous day each week.After modeling,all the rats were seperated into normal group and model group and drug treatment group and drug treatment group included curcumin,curcumin nanoparticle preparation mPEG-PLGA with low dose and high dose,each group had tweleve rats.Normal group and model group were given saline intragastrically by the same dose,and rats in drug treatment group were treated separately with curcumin（50mg·kg-1.d-1）and curcumin nanoparticle preparation mPEG-PLGA with low dose（10mg·kg-1.d-1） and high dose（30mg·kg-1.d-1） for 4 weeks.All the rats were sacrificed to harvest blood and liver tissue sample.Serum alanine aminotransferase（ALT） and aspartate transferase（AST） were detected.Content of hydroxyproline（Hyp）,Maleic Dialdehyde（MDA）,superoxide dismutase（SOD）,glutathione peroxidase（GSH-PX） and Glutathiones S transferase（GST） in liver tissue were assayed biochemically.The changes with collagen deposition in rat liver tissue were observed.Results：1.Compared to normal group,serum ALT and AST activity in model group elevated significantly（P﹤0.05）.Compared to model group,Serum ALT and AST activity in drug treatment group lowered significantly（P﹤0.05）.2.Compared to normal group,Hyp content in liver tissue in model group increased significantly（P﹤0.05）.Compared to model group,Hyp content in liver tissue in drug treatment group decreased significantly（P﹤0.05）.3.Inflammatory cells infiltration,increased collagen deposition,and pseudolobule were seen in liver tissue in model group,some histological improvements were seen in drug treatment group.4.Compared to normal group,SOD and GSH-PX activity in liver tissue in model group decreased obviously（P﹤0.01）,meanwhile,MDA and GST activity increased obviously（P﹤0.01）.Compared to model group,drug treatment group can be seen increased SOD and GSH-PX activity and decreased MDA and GST activity（P﹤0.01）.Conclusion：The curcumin nanoparticle preparation mPEG-PLGA can reverse liver fibrosis in rats and improve liver function significantly,it also can block and reverses development and formation of liver fibrosis induced by dimethylnitrosamine by protecting hepatocytes to resist liver injury and decreasing synthesis of collagen and inhibiting oxidative stress.