当飞利肝宁胶囊调控炎性小体改善非酒精性脂肪肝病大鼠肝损伤敏感性  

Dangfei Liganning Capsule ameliorate susceptibility of liver injury in NAFLD rats through regulating inflammasome

作　　者：徐娇雅[1] 肖铁刚 舒祥兵[1] 李中平[1] 宋海燕[1] 张莉[1] 季光[1,3] 

机构地区：[1]上海中医药大学附属龙华医院脾胃病研究所,上海200032 [2]上海市第六人民医院中医科,上海200233 [3]上海市高校中医内科学E-研究院,上海201203

出　　处：《中华中医药杂志》2015年第5期1580-1584,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81273727;No.81302927);上海市教育委员会科研创新项目(No.E03008;No.2012JW39;No.2012JW23);上海市浦东新区卫生局项目(No.PW2012A-40);上海中医药大学研究生"创新能力培养"专项科研项目(No.80022)~~

摘　　要：目的:探索当飞利肝宁胶囊对非酒精性脂肪性肝病(NAFLD)大鼠肝损伤敏感性的防治作用及潜在机制。方法:雄性Wistar大鼠随机分为6组,正常组(NCD)、正常饮食加CCl4组(NCD-CCl4)、高脂饮食组(HFD)、高脂饮食加CCl4组(HFD-CCl4)、当飞利肝宁胶囊组(DF)、甘草酸二铵组(G)。NCD、NCD-CCl4组大鼠喂食普通饲料,余大鼠均喂食高脂饲料,且DF、G组同时分别采用两药灌胃干预。8周后,除NCD、HFD组外,其余各组大鼠均腹腔注射CCl4造成大鼠急性肝损伤,并于48h后处死大鼠,收集血清和肝组织。检测各组大鼠血清白蛋白(ALB)、谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)水平;实时荧光定量PCR法检测肝脏组织NLRP3、ASC、Caspase-1、Pannexin、IL-1β、IL-18、IL-33 m RNA的表达,Western blot法检测肝组织核因子-κB(NF-κB)蛋白表达。结果:对正常大鼠不构成肝损伤的小剂量CCl4可使高脂饮食诱导的NAFLD大鼠肝组织炎性损伤显著加剧,血清GGT、ALP水平明显升高,NLRP3炎性小体相关基因的表达及NF-κB蛋白的表达显著升高(P<0.05);而当飞利肝宁胶囊组和甘草酸二铵组各指标均得到明显改善(P<0.05)。结论:NAFLD大鼠肝细胞损伤敏感性增加,当飞利肝宁胶囊可有效改善NAFLD大鼠的肝细胞损伤敏感性,降低NLRP3炎性小体相关基因的表达及NF-κB蛋白的表达,从而减轻肝脏炎性损伤、保护肝细胞可能是当飞利肝宁胶囊防治NAFLD大鼠肝细胞损伤敏感性的作用机制之一。Objective： To study the effects and potential mechanism of Dangfei Liganning Capsule （DF） in ameliorating liver susceptibility to injury in nonalcoholic fatty liver disease （NAFLD） rats. Methods： Male Wistar rats were randomly divided into 6 groups： NCD group, NCD-CC14 group, HFD group, HFD-CC14 group, DF group, and Diammonium Glycyrrhizinate （G） group. The rats in NCD and NCD-CC14 groups were fed with a normal chow diet （NCD）, and the rest rats were fed with a high fat diet （HFD） to induce NAFLD. In addition, the rats in DF group and G group were respectively administrated DF or G. Eight weeks later, rats were intraperitoneally injected with a nonlethal dose of CCi4 48 hours before being sacrificed. Serum and liver tissues were collected. Levels of ALB, GGT, ALP in serum were tested. The hepatic NLRP3, ASC, Caspase-1, Pannexin, IL-1β, IL-18, IL-33 mRNA expression and NF-xB protein expression were assessed. Results： There was almost no response to the nonlethal dose of CCl4 in the NCD group. However, high fat diet induced NAFLD rats emerged apparent liver injury after CC14 injection, which demonstrated elevated levels of serum GGT and ALP, liver NLRP3 inflammasome-related mRNA expression and NF-teB protein expression were also dramatically increased （P〈0.05）. DF and G treatment led to improvements in all of the above examined indexes （P〈0.05）. Conclusion： NAFLD rats expressed increased liver susceptibility to injury, which could be effectively ameliorated by DF. The function of down-regulating NLRP3 inflammasome-related mRNA expression and NF-κB protein expression to alleviate liver injury and protect liver ceils might be one of the action mechanisms of DF.

关 键 词：非酒精性脂肪性肝病 当飞利肝宁胶囊 肝损伤 炎性小体 

分 类 号：R285.5[医药卫生—中药学]