Nrf2减轻小鼠非酒精性脂肪性肝炎

NF-E2-related factor2 alleviates non-alcoholic steatohepatitis in mice

目的研究Nrf2对小鼠非酒精性脂肪性肝炎(NASH)的作用及其可能机制。方法通过蛋氨酸-胆碱缺乏饲料(MCD)饲喂小鼠获得NASH模型;随机分为对照组、模型组以及Nrf2组,Nrf2组灌胃姜黄素0.9 mL/d,对照组和模型组给予相应体积的0.9%氯化钠注射液灌胃。4周后检测肝组织中Nrf2含量,肝指数,血清谷丙转氨酶(ALT)、谷草转氨酶水平(AST)、葡萄糖(GLU)、三酰甘油(TG)和胆固醇(Chol)含量;对肝脏进行油红O染色;检测肝组织中TG、Chol、丙二醛(MDA)和谷胱甘肽(GSH)含量及超氧化物歧化酶(SOD)的活性;并检测细胞色素C和ATP含量。结果与模型组小鼠相比,Nrf2组小鼠的血清中ALT,AST和GLU含量下降(P<0.05),肝组织中TG、Chol和MDA含量下降(P<0.05),GSH水平、SOD活性升高(P<0.05);同时细胞色素C漏出降低,ATP含量上升(P<0.05)。结论 Nrf2对由蛋氨酸-胆碱缺乏所引起的NASH具有一定的保护作用,其机制可能是通过减少氧化应激,提高线粒体活性实现的。

Objective To investigate the clinical significance of NF-E2-related factor2 in preventing and treating non-alcoholic steatohepatitis（NASH）. Methods C57BL/6 mice were randomly divided into control group （con trol） , model group （MCD） and curcumin induced Nrf2 group （MCD ＋ curcumin）. Mice in control group were fed with a standard diet while those in other two groups were fed with methionine choline-deficient （MCD） diet. At the same time, mice in Curcumin induced Nrf2 group were gavaged with 0. 9 mL of curcumin daily. Control group and MCD group were gavaged with equal water. 4 weeks later, Nrf2 expression level, liver index, serum ALT and AST levels, serum triglyceride （TG）, cholesterol （Chol） and GLU contents were measured, the HE and oil red O stai ning of liver cross section were observed, hepatic TG, Chol levels, MDA contents, GSH levels and SOD activity were quantified. Cytochrome c and ATP are also measured to investigate the mitochondrial function. Results After gavaged with Curcumin, compared to MCD group, the mice＇s liver showed decreased lipid accumulation, serum ALT,AST, MDA, hepatic TG, Chol, and elevated serum TG and Chol levels. MDA level, Cytochrome c level also de crease, while GSH contents, SOD activity and the content of ATP increase （P 〈 0. 05）. Conclusions Nrt2 has the effect of protection of NASH from MCD diet and primarily through the way of reducing oxidative stress and increas ing mitochondrial function.