首页|基于TLR4/MYD88/NF-κB通路研究降脂通脉饮对高脂血症模型大鼠的影响

基于TLR4/MYD88/NF-κB通路研究降脂通脉饮对高脂血症模型大鼠的影响

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目的:基于Toll样受体4(Toll-like receptor 4,TLR4)/髓样分化因子 88(myeloid differentiation factor 88,MYD88)/核转录因子-κB(nuclear transcription factor-κB,NF-κB)通路探讨降脂通脉饮对高脂血症模型大鼠的影响.方法:从 15 只SD大鼠中随机选取3 只作为空白组,其余大鼠给予高脂饲料2 周建立高脂血症模型.将造模成功的大鼠随机分为模型组、降脂通脉饮低剂量组(1.56 mg·kg-1)、降脂通脉饮中剂量组(3.125 mg·kg-1)、降脂通脉饮高剂量组(6.25 mg·kg-1),每组各 3只,给予相应剂量药物8 周,每日1 次,空白组和模型组给予生理盐水灌胃.全自动生化仪检测大鼠血清血脂水平,包括总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C);ELISA 检测血清炎症因子含量,包括肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)、干扰素-γ(interfer-on-γ,IFN-γ);Western Blot和qPCR检测颈动脉组织TLR4、MYD88、NF-κB蛋白和基因表达水平.结果:与空白组比较,模型组大鼠血清TC、TG、LDL-C水平升高(P<0.01);与模型组比较,降脂通脉饮低剂量组、中剂量组、高剂量组大鼠血清TC、TG、LDL-C水平降低(P<0.05);各组大鼠血清HDL-C水平比较,差异无统计学意义(P>0.05).与空白组比较,模型组大鼠血清MCP-1、TNF-α、IFN-γ含量升高(P<0.01);与模型组比较,降脂通脉饮中剂量、高剂量组大鼠血清 MCP-1、TNF-α、IFN-γ含量降低(P<0.05),降脂通脉饮低剂量组大鼠血清TNF-α、IFN-γ含量降低(P<0.05).与空白组比较,模型组大鼠颈动脉组织TLR4 mRNA、MYD88 mRNA、NF-κB mRNA表达水平升高(P<0.01);与模型组比较,降脂通脉饮低剂量、中剂量、高剂量组大鼠颈动脉组织TLR4 mRNA、MYD88 mRNA、NF-κB mRNA表达水平降低(P<0.05).与空白组比较,模型组大鼠颈动脉组织TLR4、MYD88、NF-κB蛋白表达水平升高(P<0.01);与模型组比较,降脂通脉饮中剂量、高剂量组大鼠颈动脉组织TLR4、MYD88、NF-κB蛋白表达水平降低(P<0.05).结论:降脂通脉饮可降低高脂血症大鼠血脂水平,其机制可能与抑制TLR4/MYD88/NF-κB通路,从而减轻炎症反应有关.
The Influence of Granules for Invigorating Circulation and Reducing Blood Lipid on Hyperlipidemia Model Rats Based on TLR4/MYD88/NF-κB Pathway
Objective:To study the influence of Granules for Invigorating Circulation and Reducing Blood Lipid(GICRBL)on hyperlipi-demia model rats based on Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MYD88)/nuclear transcription factor-κB(NF-κB)pathway.Methods:A total of 3 from 15 SD rats were randomly selected as the blank group,and the other rats were given high-fat diet for 2 weeks to establish the hyperlipidemia model.The successfully established model rats were randomly divided into the model group,the low-dose GICRBL group(1.56 mg·kg-1),the medium-dose GICRBL group(3.125 mg·kg-1),and the high-dose GI-CRBL group(6.25 mg·kg-1),with3 rats in each group.The rats in the corresponding groups were giventhe corresponding doses of drugs for 8 weeks,once a day,while the blank group and the model group were given normal saline by gavage.The serum lipid levels of rats were detected by automatic biochemical instrument,including total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C).The serum inflammatory factors were detected by ELISA,in-cluding tumor necrosis factor-α(TNF-α),monocyte chemoattractant protein-1(MCP-1),and interferon-γ(IFN-γ).The protein and gene expression levels of TLR4,MYD88,and NF-κB in carotid artery tissue were detected by Western Blot and qPCR.Results:Com-pared with the blank group,the serum TC,TG and LDL-C levels of the model group were increased(P<0.01).Compared with the model group,the serum TC,TG and LDL-C levels of the low-dose GICRBL group,the medium-dose GICRBL group,and the high-dose GICRBL group were decreased(P<0.05).There was no significant difference in the serum HDL-C level among the groups(P>0.05).Compared with the blank group,the serum MCP-1,TNF-α,and IFN-γ contents of rats in the model group were significantly in-creased(P<0.01).Compared with the model group,the contents of MCP-1,TNF-α and IFN-γ in the serum of rats in the medium-dose and high-dose GICRBL groups were decreased(P<0.05),and the contents of TNF-α and IFN-γ in the serum of rats in the low-dose GI-CRBL group were decreased(P<0.05).Compared with the blank group,the expression levels of TLR4 mRNA,MYD88 mRNA,and NF-κB mRNA in the carotid artery tissue of rats in the model group were significantly increased(P<0.01).Compared with the model group,the expression levels of TLR4 mRNA,MYD88 mRNA and NF-κB mRNA in the carotid artery tissue of rats in the low-dose,medium-dose and high-dose groups of Jiangzhitongmaiyin were decreased(P<0.05).Compared with the blank group,the protein expression levels of TLR4,MYD88 and NF-κB in the carotid artery tissue of rats in the model group were significantly increased(P<0.01).Compared with the model group,the protein expression levels of TLR4,MYD88 and NF-κB in the carotid artery tissue of rats in the medium-dose and high-dose groups of GICRBL were significantly decreased(P<0.05).Conclusion:GICRBL can reduce the blood lipid level in hyperlipi-demic rats,and its mechanism may be related to inhibiting TLR4/MYD88/NF-κB pathway,thereby reducing inflammatory response.

hyperlipidemiagranules for invigorating circulation and reducing blood lipid(GICRBL)blood lipidTLR4/MYD88/NF-κB pathwayinflammationrats

郭锦荣、朱立新、彭垒、张鞠华、周芬敏、陆瑞峰

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上海健康医学院附属周浦医院,上海 201318

高脂血症 降脂通脉饮 血脂 TLR4/MYD88/NF-κB通路 炎症 大鼠

上海市浦东新区卫生健康委员会中医药传承创新发展示范试点项目上海市浦东新区科技和经济委员会民生科研专项资金医疗卫生项目

YC-2023-0127PKJ2019-Y41

2024

河南中医
河南省中医药学会 河南中医学院

河南中医

影响因子:0.968
ISSN:1003-5028
年,卷(期):2024.44(3)
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