泻浊调脂方调控TLR4/MyD88/p38 MAPK信号通路改善脂代谢及炎症反应OA
Xiezhuo Tiaozhi Formula Improves Lipid Metabolism and Inflammatory Response by Regulating the TLR4/MyD88/p38 MAPK Signaling Pathway
[目的]研究泻浊调脂方对非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)模型小鼠脂代谢和炎症反应的调节作用,并探讨其相关机制.[方法]采用高脂饲料(60%能量来源于脂肪)和高糖饮用水(含55%果糖)喂养,建立NAFLD小鼠模型,泻浊调脂方低、中、高剂量予泻浊调脂方2.08、4.16、8.32 g·kg-1灌胃,阳性对照组予多烯磷脂酰胆碱胶囊内容物0.2 g·kg-1灌胃.检测各组小鼠体质量、肝脏质量、肝脏脂质含量及血清各项生化指标水平;HE染色和油红O染色观察小鼠肝组织病理学变化和脂质沉积情况;Real-time qPCR检测固醇调节元件结合蛋白1c(sterol regulatory element-binding protein 1c,SREBP1c)、白细胞分化抗原36(cluster of differentiation 36,CD36)、激素敏感性脂肪酶(hormone-sensitive triglyceride lipase,HSL)、肉碱棕榈酰转移酶 1α(carnitine palmitoyltransferase 1α,CPT1α)、TNF-α、IL-6、IL-1β、NOD样受体热蛋白结构域3(NOD like receptor family pyrin domain containing 3,NLRP3)、Toll样受体4(Toll-like receptor 4,TLR4)、髓样分化因子88(myeloid differentiation factor 88,MyD88)mRNA表达情况;免疫印迹法检测SREBP1c、CD36、TLR4、MyD88、p38 丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)、磷酸化p38丝裂原活化蛋白激酶(phosphorylated-p38 mitogen-activated protein kinase,p-p38 MAPK)的蛋白表达情况.[结果]与模型组比较,泻浊调脂方可有效降低NAFLD小鼠的肝脏质量(P<0.01),减少肝脏脂质沉积,减轻肝损伤,降低血脂(P<0.01),抑制脂质合成因子SREBP1c、CD36的mRNA和蛋白表达,促进脂质分解因子CPT1α、HSL的mRNA表达,降低炎症因子IL-6、IL-1β、TNF-α、NLRP3的mRNA表达,降低TLR4、MyD88的表达,减少p38 MAPK的磷酸化(P<0.01).[结论]泻浊调脂方通过下调TLR4/MyD88/p38 MAPK信号通路,改善NAFLD小鼠的脂代谢,降低炎症因子表达.
[Objective]To study the regulatory effect of Xiezhuo Tiaozhi Formula on lipid metabolism and inflammatory response in nonalcoholic fatty liver disease(NAFLD)model mice.[Methods]The NAFLD mice model was established with high-fat diet(60%energy from fat)and high-sugar drinking water(containing 55%fructose),Xiezhuo Tiaozhi Formula was administered by gavage at low,medium and high doses of 2.08,4.16 and 8.32 g·kg-1,respectively;the positive control group was administered by gavage with the contents of Polyene phosphatidylcholine capsule at 0.2 g·kg-1.The body weight,liver weight,liver lipid content and serum biochemical indexes were detected.Liver histopathology and lipid deposition were observed by HE staining and oil red O staining.The mRNA expression of sterol regulatory element-binding protein 1c(SREBP1c),cluster of differentiation 36(CD36),hormone-sensitive triglyceride lipase(HSL),carnitine palmitoyltransferase 1α(CPT1α),TNF-α,IL-6,IL-1β,NOD like receptor family pyrin domain containing 3(NLRP3),Toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88)mRNA were detected by Real-time qPCR,and Western blot was used to detect the protein expression of SREBP1c,CD36,TLR4,MyD88,p38 mitogen-activated protein kinase(p38 MAPK)and phosphorylated-p38(p-p38 MAPK).[Results]Compared with model group,Xiezhuo Tiaozhi Formula could effectively reduce the liver weight of NAFLD mice(P<0.01),decrease the liver lipid deposition,alleviate the liver injury,lower the blood lipid(P<0.01),inhibit the mRNA and protein expression of lipid synthesis factors SREBP1c and CD36,promote the mRNA expression of lipid decomposition factors CPT1α and HSL,reduce the mRNA expression of inflammatory factors IL-6,IL-1β,TNF-α and NLRP3,decrease the expression of TLR4 and MyD88,and reduce the phosphorylation of p38 MAPK(P<0.01).[Conclusion]Xiezhuo Tiaozhi Formula improves lipid metabolism and reduces the expression of inflammatory factors in NAFLD mice by down regulating TLR4/MyD88/p38 MAPK signaling pathway.
陈坤铃;窦晓兵;邱剑楠;林益游;白丹瑶;罗杨舟;周丽萍
浙江中医药大学生命科学学院 杭州 310053浙江中医药大学生命科学学院 杭州 310053浙江中医药大学生命科学学院 杭州 310053浙江中医药大学生命科学学院 杭州 310053浙江中医药大学生命科学学院 杭州 310053浙江中医药大学生命科学学院 杭州 310053浙江中医药大学生命科学学院 杭州 310053
医药卫生
非酒精性脂肪性肝病多烯磷脂酰胆碱泻浊调脂方中药复方脂代谢炎症因子TLR4MAPK
non-alcoholic fatty liver diseasepolyene phosphatidylcholineXiezhuo Tiaozhi FormulaCompound Chinese Medicine Formulaslipid metabolisminflammatory factorsTLR4MAPK
《浙江中医药大学学报》 2026 (3)
278-287,10
国家自然科学基金项目(82374102、82004353)浙江省自然科学基金项目(LQ20H290005)杭州市农业与社会发展科研重点项目(202204A04)浙江中医药大学科研项目(2022JKZKTS21) National Natural Science Foundation Project(82374102,82004353)Zhejiang Provincial Natural Science Foundation Project(LQ20H290005)Key Scientific Research Project of Agriculture and Social Development in Hangzhou City(202204A04)Zhejiang Chinese Medical University Research Project(2022JKZKTS21)
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