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目的基于肝组织差异蛋白质组表达,解析下瘀血汤对硫代乙酰胺诱导的肝硬化进展期大鼠的作用及其机制。方法48只SD雄性大鼠中的18只作为对照组,其余30只ip给予40 mg/mL的硫代乙酰胺水溶液200 mg/kg制备大鼠肝硬化模型,每周2次,连续8周;于开始造模后第4周分别随机处死对照组和造模大鼠各6只,进行药物干预前的动态观察。其余模型大鼠于开始造模后第5周首日随机分为模型组及下瘀血汤组,下瘀血汤组大鼠ig给予下瘀血汤0.626 g/kg,对照组和模型组大鼠ig生理盐水;于第8周末处死大鼠,双向凝胶电泳分离肝组织总蛋白,基质辅助激光解析电离飞行时间质谱分析鉴定部分差异表达蛋白;蛋白质免疫印迹法检测层粘连蛋白受体(67 LR)、DJ-1蛋白、Cu-Zn超氧化物歧化酶(Cu-Zn SOD)蛋白表达。结果鉴定的18个蛋白中有5个氧化应激蛋白、5个与物质代谢相关的蛋白、4个细胞骨架蛋白、2个与炎症反应相关的蛋白、2个与增殖凋亡相关的蛋白;验证的3个蛋白点(67 LR、Cu-Zn SOD、DJ-1)与双向电泳分析结果基本一致。结论过氧化损伤以及造成的物质代谢异常是硫代乙酰胺致大鼠肝硬化的重要病理环节,提高机体内在的抗氧化能力及逐步恢复物质代谢能力是下瘀血汤逆转大鼠肝硬化的主要机制之一。
OBJECTIVE: To elucidate the effects of Xiayuxue decoction on thioacetamide-induced hepatic cirrhosis in rats and its mechanism based on the differential expression of proteome in liver tissue. Methods Eighteen 48 male Sprague Dawley rats were used as the control group, and the other 30 rats were given 40 mg / mL thioacetamide solution 200 mg / kg to prepare rat liver cirrhosis model twice a week for 8 weeks. At the 4th week after model establishment, 6 rats in control group and model group were randomly sacrificed, and the dynamic observation before drug intervention was performed. The rest of the model rats were randomly divided into model group and Xiayuxue soup group on the first week of the fifth week after modeling. The rats in Xiayuxue soup group were given 0.626 g / kg of Xiayu decoction ig, the control group and the model group were Rats were sacrificed at the end of 8th week, and the total protein in liver tissues was separated by two-dimensional gel electrophoresis. Some differentially expressed proteins were identified by matrix-assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF-MS), and the laminin receptor LR), DJ-1 protein and Cu-Zn superoxide dismutase (Cu-Zn SOD) protein expression. Results Among the 18 proteins identified, there were 5 oxidative stress proteins, 5 proteins related to metabolism, 4 cytoskeletal proteins, 2 proteins related to inflammation and 2 proteins related to proliferation and apoptosis. The three protein spots (67 LR, Cu-Zn SOD, DJ-1) were consistent with the two-dimensional electrophoresis. Conclusions Peroxidation injury and substance metabolism abnormalities are the important pathological steps of thioacetamide induced cirrhosis of the liver in rats. It can enhance the intrinsic antioxidant capacity and gradually restore the substance metabolism ability of Xiaheyu Decoction to reverse the cirrhosis of rats One of the main mechanisms.