FGF21对非酒精性脂肪肝大鼠肝细胞TLR4/p38MAPK通路的影响  

Effect of FGF21 on TLR4/p38MAPK Signaling Pathway in Nonalcoholic Fatty Liver Diseases of Rats

作　　者：车兴影 韩继武[1] Che Xingying;Han Jiwu(The Fourth Affiliated Hospital of Harbin Medical University,Heilongjiang 150000,China)

机构地区：[1]哈尔滨医科大学附属第四医院,150000

出　　处：《医学研究杂志》2018年第5期130-135,共6页Journal of Medical Research

摘　　要：目的探讨成纤维细胞生长因子21(FGF21)对谷氨酸钠(MSG)诱导非酒精性脂肪肝大鼠肝细胞炎症及TLR4/p38MAPK信号通路的影响。方法新生SD大鼠随机分成正常对照组、MSG组和FGF21组(n=10)。MSG组和FGF21组大鼠于生后第2、4、6、8、10天皮下注射MSG 4g/(kg·d)喂养至13周,FGF21组大鼠腹腔注射FGF21 1mg/(kg·d)32天。HE染色分析肝脏病理学改变;观察肝重、肝功能;qRT-PCR和Western blot法检测肝组织IL-6、TNF-α、TLR4、p38MAPK表达情况。结果与正常对照组比较,MSG组大鼠肝细胞发生脂肪变性伴炎性细胞浸润,肝重、ALT、AST、ALP水平升高(P<0.01),肝细胞IL-6、TNF-α、TLR4、p38MAPK mRNA表达增加(P<0.01),TLR4、p38MAPK、p-p38MAPK蛋白表达升高(P<0.01);与MSG组比较,FGF21组大鼠肝细胞脂泡和炎性细胞减少,肝重、ALT、AST、ALP降低(P<0.05,P<0.01,P<0.01,P<0.05),IL-6、TNF-α、TLR4、p38MAPK mRNA表达下降(P<0.01),TLR4、p38MAPK、p-p38MAPK蛋白水平降低(P<0.01)。结论 FGF21可能通过调节TLR4/p38MAPK信号转导通路,抑制NAFLD炎性反应。Objective To explore the effect of FGF21 on MSG-induced nonalcoholic fatty liver diseases of inflammation and TLR4/p38MAPK signal pathway in rats. Methods Newborn SD rats were randomly divided into control group,MSG group and FGF21 group（ n= 10）.Rats of MSG group and FGF21 group were adiministered with solution of MSG 4g/（kg·d） at 2nd,4th,6th,8th and 10th postnataldays.After being fed for thirteen weeks,rats of FGF21 group was intraperitoneal injected with FGF21 1mg/（kg·d） for a continuous 32 days.Liver pathology of the rats was analyzed by HE staining.The liver weight,aminotrasferases were observed.The expression of IL- 6,TNF-α,TLR4,p38MAPK in liver tissue were determined by fluorescence quantitative PCR and Western blot. Results Compared with the control group,liver tissues of the MSG group changed to bullous steatosis and had inflammatory cell infiltration,the liver weighted,serum activities of ALT,AST,ALP were increased（ P 〈0.01, P 〈0.01, P 〈0.01, P 〈0.01）.The expression of IL-6,TNF-α,TLR4,p38MAPK mRNA and protein expression of TLR4,p38MPAK,p-p38MAPK in rats hepatocyte were increased than those in control group （ P 〈0.01）.After reatment with FGF21,the bullous steatosis and inflammatory cell,liver weighted,serum activities of ALT,AST,ALP were signficantly decreased（ P 〈0.05, P 〈0.01, P 〈0.01, P 〈0.05）,and the levels of IL-6,TNF-a,TLR4,p38MAPK mRN A and protein expression of TLR4,p38-MPAK,p-p38MAPK were reduced than those of MSG group（ P 〈0.01）. Conculsion The FGF21 may regulate MSG-induced NAFLD of inflammation through TLR4/p38MAPK signaling pathway in rats.

关 键 词：成纤维细胞生长因子21 非酒精性脂肪性肝病 TLR4/p38MAPK信号通路 

分 类 号：R453.9[医药卫生—治疗学]