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鳄嘴花对代谢相关脂肪性肝病小鼠TLR4/MyD88/NF-κB信号通路的影响

Effects of Clinacanthus Nutans on TLR4/MyD88/NF-κB Signaling Pathway in Mice with Metabolic Associated Fatty Liver Disease

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【作者】 张文霞吴惠妃杨静戴卫波钟希文

【Author】 ZHANG Wenxia;WU Huifei;YANG Jing;DAI Weibo;ZHONG Xiwen;Zhongshan Hospital of Traditional Chinese Medicine Afiliated to Guangzhou University of Chinese Medicine;

【通讯作者】 钟希文;

【机构】 广州中医药大学附属中山市中医院

【摘要】 目的 探讨鳄嘴花对高脂饲料诱导的代谢相关脂肪性肝病(MAFLD)模型小鼠TLR4/MyD88/NF-κB信号通路的影响。方法 将SPF级雄性C57BL/6J小鼠随机分为正常组(10只)和造模组(43只),正常组给予普通饲料,造模组予高脂饲料喂养12周,建立MAFLD小鼠模型。造模成功后,将造模组小鼠随机分为模型组及鳄嘴花低、中、高(7.74、15.48、30.96 g·kg-1)剂量组,每组10只。正常组、模型组给予灭菌水灌胃,鳄嘴花给药组按10 mL·kg-1给予相应剂量药液灌胃,每日1次,连续4周。检测各组小鼠血清甘油三酯(TG)、总胆固醇(TC)、天门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)水平;采用HE染色法观察肝脏组织病理变化;Real-Time PCR法及Western Blot法检测小鼠肝脏组织TLR4、MyD88、NF-κB、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)mRNA及蛋白表达情况。结果 与正常组比较,模型组小鼠的体质量及血清ALT、AST、TC、TG水平均显著升高(P<0.01),肝脏组织中TLR4、MyD88、NF-κB、TNF-α、IL-6蛋白及mRNA表达均显著上调(P<0.01)。与模型组比较,鳄嘴花给药组小鼠的体质量及血清ALT、AST、TC、TG水平明显降低(P<0.05,P<0.01),肝脏组织中TLR4、MyD88、NF-κB、TNF-α、IL-6蛋白及mRNA表达均显著下调(P<0.05,P<0.01)。结论 鳄嘴花能够改善MAFLD小鼠的脂质代谢及肝损伤,可能与其抑制TLR4/MyD88/NF-κB信号通路的表达有关。

【Abstract】 Objective To investigate the effects of Clinacanthus nutans on the TLR4/MyD88/NF-κB signalling pathway in a high-fat diet-induced metabolic associated fatty liver disease(MAFLD)model mouse.Methods SPF male C57BL/6J mice were randomly divided into the normal group(10 mice)and the modeling group(43 mice),and the normal group was fed with normal diet while the modeling group was fed with high-fat diet for 12 weeks to establish the MAFLD mouse model. After successful modelling, the mice in the modelling group were randomly divided into the model group and the Clinacanthus nutans low-,medium-and high-(7.74,15.48 and 30.96 g·kg-1)dose groups with 10 mice in each group. The normal group and the model group were given sterile water by gavage,while the Clinacanthus nutansr administration group was given the corresponding dose by gavage at 10 mL·kg-1once dailly for 4 continuous weeks. Serum triglyceride(TG),total cholesterol(TC),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels were measured in each group;The pathological changes of liver tissue were observed by the HE staining method;The mRNA expressions and protein expressions of TLR4,MyD88,NF-κB,TNF-α,IL-6 in mice liver tissues were detected by the Real-Time PCR method and the Western Blot method.Results Compared with the normal group, the body mass and serum levels of ALT, AST, TC and TG were significantly increased in the model group(P<0.01), and the protein expressions and the mRNA expressions of TLR4,MyD88,NF-κB,TNF-α,IL-6 in liver tissues were significantly upregulated(P<0.01). Compared with the model group, the body mass and serum ALT, AST, TC and TG levels of mice in the Clinacanthus nutans administration group were significantly reduced(P<0.05, P<0.01), and the protein expressions and the mRNA expressions of TLR4,MyD88,NF-κB,TNF-α,IL-6 in liver tissues were significantly down-regulated(P<0.05,P<0.01).Conclusion Clinacanthus nutans has effect in improving lipid metabolism and liver injury in MAFLD mice,which may be related to its inhibition of TLR4/MyD88/NF-κB signaling pathway expression.

【基金】 中山市社会公益科技研究项目(2019B1078)
  • 【文献出处】 中药新药与临床药理 ,Traditional Chinese Drug Research and Clinical Pharmacology , 编辑部邮箱 ,2022年05期
  • 【分类号】R285.5
  • 【被引频次】1
  • 【下载频次】281
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