复方楂金颗粒对NASH小鼠肝脏内TLR4信号通路的影响  

Effect of Compound Zhajin Granule on Toll-like Receptor 4 Signaling Pathway in Nonalcoholic Steatohepatitis Mice

作　　者：刘静[1] 庄振杰[1] 田静 李兆翌 罗燕[1] 柳银兰[1] 陈建玉[1] 马晓洁[1] 臧淑妃[3] 施军平[3] 

机构地区：[1]杭州师范大学附属医院肝病科,杭州310015 [2]浙江省杭州市西溪医院药剂科,杭州310014 [3]杭州师范大学附属医院内分泌科,杭州310015

出　　处：《中国中西医结合杂志》2016年第4期460-465,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金面上项目(No.81070316);浙江省杭州市科技计划项目(No.2006533Q13)

摘　　要：目的观察复方楂金颗粒对高脂高果糖饮食诱导的非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)小鼠肝脏内Toll样受体4(Toll-like receptor 4,TLR4)信号通路影响。方法 6周龄雄性C3H品系小鼠30只,按体重分层随机分为高脂高果糖组(20只)和对照组(10只)。高脂高果糖组用高脂饲料和20%果糖饮用水喂养;对照组用普通饲料和普通饮用水喂养。8周后将高脂高果糖组按体重分层随机分为高脂高果糖组和楂金颗粒组各10只,楂金颗粒组用高脂饲料和20%果糖饮用水喂养,每天按50mL/kg予12.8%的复方楂金颗粒冲剂灌胃(山楂、郁金、泽泻、海藻、象贝、水飞蓟、桃仁按3∶1.5∶1.5∶2∶1.5∶2∶1比例制备而成)。余组喂养如前,每天予同体积蒸馏水灌胃,16周处死小鼠。检测小鼠体重、肝湿重、肝功能及脂代谢指标,采用HE、油红O及Masson染色评价小鼠肝脏病理学改变。用免疫组织化学染色和实时荧光定量PCR法检测小鼠肝组织TLR4、髓样分化因子88(myeloid differentiation factor 88,MyD88)、肿瘤坏死因子(tumor necrosis factor-alpha,TNF-α)表达。结果楂金颗粒组体重、谷丙转氨酶(alanine aminotransferase,ALT)、谷草转氨酶(aspartate aminotransferase,AST)明显低于高脂高果糖组(P<0.05);油红O染色面积、密度较对照组减少;HE染色显示,楂金颗粒组炎症气球样变较高脂高果糖组减少;Masson染色阴性;TLR4、MyD88免疫组化染色阳性率和mRNA表达均明显低于高脂高果糖组(P<0.05)。结论复方楂金颗粒剂能明显抑制NASH小鼠肝脏内TLR4信号通路。Objective To observe the effect of Compound Zhajin Granule（CZG）on Toll-like receptor 4（TLR4）signaling pathway in high-fructose corn syrup induced NASH mice.Methods Thirty 6-week-old male C3 H mice were divided into the high fat and high fructose（HFHFr）group（n=20）and the control group（n=10）according to body weight.Mice in the HFHFr group ate high fat diet and drank20%fructose water,while those in the control group ate common diet and drank common water.After 8 weeks mice in the HFHFr group were divided into two group according to body weight,the HFHFr group and the CZG group,10 in each group.Mice in the CZG group were fed with high fat forage and 20% fructose water,and administered with 50 mL/kg 12.8% CZG（prepared by hawthorn,Radix Curcumae,Alisma Orientale,Fritillaria Thunbergii,Silybum Marianum,peach seed in the ratio of 3∶1.5∶1.5∶2∶1.5∶2∶1）by gastrogavage.Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage.Sixteen weeks later all mice were sacrificed.Body weight,liverwet weight,liver function,and lipid metabolism were detected.Pathological changes of liver tissues were assessed by HE staining,oil red O staining,and Masson staining.Expressions of TLR4,myeloid differentiation factor 88（MyD88）,tumor necrosis factor-alpha（TNF-α）were detected using immunohistochemical staining and real-time fluorescent quantitative PCR.Results Body weight,alanine aminotransferase（ALT）,aspartate aminotransferase（AST）were obviously lower in the CZG group than in the HFHFr group（P〈0.05）;oil red O stained area and density were decreased more in the CZG group than in the control group.HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group.Masson staining was negative.Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group（all P〈0.05）.Conclusion CZG could significantly inhibit TLR4 signaling pat

关 键 词：非酒精性脂肪性肝炎 复方楂金颗粒 TOLL样受体4 

分 类 号：R285.5[医药卫生—中药学]