电针联合阿托伐他汀对非酒精性脂肪性肝炎大鼠肝脏病理、氧化应激反应及炎症因子的影响

Effect of electroacupuncture combined with atorvastatin on liver pathology,oxidative stress and inflammation in non alcoholic fatty liver rats

目的:探讨电针(EA)联合阿托伐他汀(ATT)对非酒精性脂肪性肝炎(NASH)大鼠肝脏病理、氧化应激反应及炎症因子变化的影响及潜在机制。方法:依据随机数字表法,将50只成年雄性SD大鼠分为5组,每组10只。即正常组、模型组、阿托伐他汀治疗组(简称药物组)、电针治疗组(简称电针组)、电针联合阿托伐他汀治疗组(简称联合组)。除正常组大鼠外,其余4组大鼠均采用高脂饮食建立NASH模型,造模成功后电针组大鼠采用电针治疗;药物组大鼠灌喂阿托伐他汀;联合组大鼠采用电针和灌喂阿托伐他汀治疗;正常组和模型组大鼠灌喂等量生理盐水,疗程均为10周。疗程结束时摘取大鼠肝脏,收集血液,采用全自动生化仪检查各组大鼠肝功能指标;采用RT-PCR法检测各组大鼠肝脏炎症因子表达水平;光镜下观察各组大鼠肝脏病理和脂肪沉积情况。结果:与模型组大鼠比较,电针组、药物组、联合组大鼠肝组织损伤程度明显降低;肝功能明显改善;脂质沉积明显减少P<0.05及P<0.001,且联合组大鼠3项指标改变最为明显,P<0.05;马松染色结果显示,与模型组大鼠比较,3个治疗组大鼠肝组织中胶原含量明显下降均P<0.05,且以联合组的指标下降最为显著;RT-PCR检测结果显示,联合组大鼠肝脏炎症因子水平下降最明显,与模型组、电针组、药物组大鼠比较,差异有显著性意义,P<0.05。结论:电针联合阿托伐他汀可明显减轻NASH大鼠肝损伤,降低炎症因子水平,减轻氧化应激反应,机制可能与其对内质网应激反应的抑制有关,且联合治疗对肝脏保护作用优于单独电针或阿托伐他汀。

Objective:To investigate the effect of electroacupuncture(EA)combined with atorvastatin(ATT)on liver pathology,oxidative stress,and inflammation in non alcoholic fatty liver disease(NASH)rats Potential mechanism.Methods:According to the method of random number table,50 adult male SD rats were randomly divided into five groups,10 rats in each group,control group,NASH group,NASH+ATT group,NASH+EA+ATT group,NASH+EA group.The liver function of rats in each group was examined and compared.NASH model was established by high-fat diet.EA group stimulated the two sides of Zusanli point by electroacupuncture,which lasted for 10 weeks,and rats in the ATT group took 20 mg/kg/D atorvastatin by gavage for 10 weeks.The related indexes were evaluated by oil red O staining,Masson staining,RT-PCR,Western blot,and H E staining.Results:HE and biochemical examination showed that compared with NASH group,the degree of liver injury and liver function of EA combined ATT group were significantly improved,and the effect was better than that of EA or ATT alone(P<0.05);oil red O staining showed that EA combined with ATT could significantly reduce lipid deposition in liver tissue of NASH rats(P<0.05).The results of Masson staining showed that the collagen content in the liver tissue of EA combined with ATT rats was lower(P<0.05).RT-PCR and Western blot showed that EA combined with ATT significantly reduced the level of inflammation in NASH rats(P<0.05).In mechanism,EA combined with ATT could significantly inhibit the expression of stress related proteins in liver tissue of NASH rats(P<0.05).Finally,we found that EA alone or EA combined with ATT had no damage to the heart,liver,and lung of rats.Results:Compared with NASH group rats,the degree of liver injury and liver function in EA combined ATT group rats were significantly improved,and the effect was better than EA or ATT alone treatment(P<0.05);EA combined with ATT can significantly reduce the liver of NASH rats Lipid deposition in tissues reduces triglyceride and free fatty acid content(P<0.05).EA combined with ATT can significantly reduce the level of inflammation and oxidative stress in liver tissue of NASH rats(P<0.05).Mechanistically,EA combined with ATT can significantly inhibit the expression of endoplasmic reticulum stress related proteins in the liver tissue of NASH rats(P<0.05).Finally,we found that EA alone or EA combined with ATT treatment had no damaging effect on rat heart,liver,and lungs.Conclusion:Electroacupuncture combined with atorvastatin can significantly reduce liver damage,inflammation,and oxidative stress induced by high-fat diet induced non alcoholic fatty liver in rats,and the mechanism may be related to its inhibition of endoplasmic reticulum stress,and Electroacupuncture combined with atorvastatin has better liver protection than electroacupuncture or atorvastatin alone.