摘要
目的:验证"膈下逐瘀汤抑制大鼠纤维化肝脏组织氧化应激的作用是通过增强硫氧还蛋白系统而实现"这一假说。方法:SD大鼠随机分为正常对照组、模型组,正常大鼠+膈下逐瘀汤组、模型大鼠+膈下逐瘀汤组。大鼠免疫性肝纤维化模型通过每周2次每只大鼠腹腔注射猪血清0.5 m L的方法制备。同时按含生药每天7.37 g·kg-1的剂量给予膈下逐瘀汤灌胃给药干预。采用分光光度法检测肝脏组织中脂质过氧化物(LipidPeroxidation,LPO)含量、硫氧还蛋白还原酶(Thioredoxin Reductase,Trx R)活性、PCR检测编码核转录因子E2相关因子2(Nuclear Factor Erythroid 2-related Factor 2,Nrf2)基因Nfe2l2的表达,利用Western blot检测硫氧还蛋白-1(Thioredoxin-1,Trx1)蛋白表达和Akt磷酸化水平。结果:与模型对照组大鼠比较,膈下逐瘀汤组大鼠纤维化肝脏组织LPO含量显著降低,Trx1蛋白表达和Trx R活性显著提高,Akt磷酸化水平显著增加,Nfe2l2 m RNA表达显著上调(均P<0.05)。结论:膈下逐瘀汤增强机体肝脏硫氧还蛋白系统与其活化Akt-Nrf2信号通路有关,从而预防大鼠纤维化肝脏组织氧化应激状态,本实验结果为支持假说提供了实验依据。
This study was aimed to verify the hypothesis that Ge-Xia Zhu-Yu （GXZY） decoction protects liver from porcine serum-induced oxidative stress through the thioredoxin system. SD rats were randomly divided into the blank control group, model group, normal rat ＋ GXZY decoction group, model rat ＋ GXZY group. The rat autoimmune hepatic fibrosis model was induced with porcine serum by intraperitoneal injection （0.5 mL/each rat） twice a week. And GXZY decoction （7.37 g raw material/kg, d） was simultaneously administered daily by gavage. Lipid peroxidation （LPO） levels and thioredoxin reductase （TrxR） activity in liver tissues were determined by the colorimetric method. Polymerase chain reaction （PCR） was used to analyze the transcription factor nuclear factor erythroid 2-related factor 2 （Nfe212, previously known as Nrf2） mRNA expression. And the western blot was used to analyze the thioredoxin-1 （Trxl） protein expression and Akt phosphorylation in the liver. The results showed that compared to the model control group, the GXZY decoction group attenuated porcine serum-induced oxidative stress, as indicated by the LPO level, in liver tissues. Furthermore, GXZY decoction significantly enhanced TrxR activity, Trxl protein expression, Nfe212 mRNA expression, and Akt phosphorylation （all P〈0.05）. It was concluded that the strong antioxidant properties of GXZY decoction in the porcine serum rat model was due to the enhancement of the hepatic thioredoxin system via activating Akt-Nrf2 signaling pathway. The study results provided experimental evidences for the supporting of this hypothesis.
作者
杨婧
贾彦
王蔚
戚基萍
刘宏
代巧妹
Yang Jing Jia Yan Wang Wei Qi Jiping Liu Hong Dai Qiaomei(Department of Pathology, College of Basic Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China)
出处
《世界科学技术-中医药现代化》
CSCD
2017年第4期701-705,共5页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委青年科学基金项目(81603418):膈下逐瘀汤干预循环miRNA治疗非酒精性脂肪性肝纤维化的机制研究
负责人:杨婧
关键词
肝纤维化
膈下逐瘀汤
氧化应激
硫氧还蛋白系统
核转录因子E2相关因子2
Hepatic fibrosis, Ge-Xia Zhu-Yu decoction, oxidative stress, thioredoxin ssystem, transcription factor nuclear factor erythroid 2-related factor 2
