基于NF-κB信号通路探讨晕清降压方治疗肥胖相关性高血压痰瘀互结证大鼠的作用机制  

Effect of Yunqing Jiangya Decoction(晕清降压方)on NF-κB Pathway in Rats with Obesity-Related Hypertension of Phlegm-Blood Stasis Syndrome

作　　者：左丽婉 张艺 田卫杰 刘春华[1] 熊向晖[1] ZUO Liwan;ZHANG Yi;TIAN Weijie;LIU Chunhua;XIONG Xianghui(The Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha Hunan 410005,China;Chongqing Fuling District Hospital of Traditional Chinese Medicine,Chongqing 408000,China)

机构地区：[1]湖南中医药大学第二附属医院,湖南长沙410005 [2]重庆市涪陵区中医院,重庆408000

出　　处：《中医药导报》2025年第3期24-29,64,共7页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：湖南省自然科学基金科药联合项目(2022JJ80021);湖南省中医药科研计划重点项目(C2022013);湖南中医药大学校级科研项目(2023YF02)。

摘　　要：目的:探究晕清降压方对肥胖相关性高血压模型大鼠核因子κB(NF-κB)炎症信号通路的影响。方法:从60只SD雄性大鼠中随机选取8只分为空白组,其余大鼠采用小剂量链脲佐菌素+高盐高脂饲料喂养+慢性束缚应激构建肥胖相关性高血压痰瘀互结证模型,根据随机数字表法将造模成功的40只雄性SD大鼠分为模型组、替米沙坦组及晕清降压方低、中、高剂量组,每组8只。晕清降压方低、中、高剂量组分别给予晕清降压方[10.0 g/(kg·d)、20.0 g/(kg·d)、40.0 g/(kg·d)]灌胃;替米沙坦组予替米沙坦片[3.5 mg/(kg·d)]灌胃;空白组及模型组大鼠给予蒸馏水[10 mL/(kg·d)]灌胃,1次/d,连续4周。测定各组大鼠血压、体质量、血脂、空腹血糖;使用酶联免疫吸附测定法检测血清脂多糖(LPS)水平;免疫印迹(Western blotting)法检测结肠组织髓分化因子88(MyD88)、p65、磷酸化NF-κB抑制蛋白(p-IκB)、p-p65蛋白表达;实时PCR法检测结肠组织白介素-1β(IL-1β)mRNA、肿瘤坏死因子-α(TNF-α)mRNA、IL-18 mRNA表达水平;苏木精-伊红(HE)染色观察大鼠肝脏及结肠病理形态。结果:与空白组相比,模型组大鼠体质量及血压升高(P<0.05),总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FBG)升高(P<0.05),高密度脂蛋白胆固醇(HDL-C)降低(P<0.05),血清LPS水平升高(P<0.01),结肠MyD88、p-IκB、p-p65、p65蛋白表达显著升高(P<0.05),结肠IL-1βmRNA、TNF-αmRNA、IL-18 mRNA表达升高(P<0.01),肝脏可见广泛散在的肝细胞脂肪变性,结肠组织结构紊乱。与模型组比较,替米沙坦组及晕清降压方各剂量组大鼠体质量及血压均降低(P<0.05),LDL-C、FBG均降低(P<0.05),HDL-C升高(P<0.05),晕清降压方高剂量组TG及LPS降低(P<0.01);与模型组相比,晕清降压方低、中、高剂量组大鼠结肠MyD88、p-IκB、p-p65、p65蛋白表达显著下降(P<0.01),结肠组织IL-1βmRNA、TNF-αmRNA、IL-18 mRNA表达显著�Objective:To investigate the effects of Yunqing Jiangya decoction on NF-κB inflammatory signaling pathway in obesity-related hypertension model rats with phlegm-blood stasis syndrome.Methods:A total of 8 rats were selected as control group from 60 male Sprague-Dawley(SD)rats,and the remaining rats subjected to a combination of low-dose STZ,high-salt high-fat diet,and chronic restraint stress to establish a hypertensive obese rat model with phlegm-blood stasis syndrome.The 40 male SD model rats were further randomized into model group,telmisartan group,low-dose Yunqing Jiangya Decoction group,medium-dose Yunqing Jiangya decoction group,and high-dose Yunqing Jiangya decoction group,8 rats in each group.Rats in the low,medium,and high-dose Yunqing Jiangya decoction groups received oral gavage of low dose[10.0 g/(kg·d)],medium dose[20.0 g/(kg·d)],and high dose[40.0 g/(kg·d)]of Yunqing Jiangya decoction,respectively,while the telmisartan group received telmisartan at a dose of 3.5 mg/(kg·d).The control group and model group received distilled water[10.0 mL/(kg·d)]by oral gavage.Treatment was administered once daily for four weeks.Blood pressure,body mass,blood lipid and fasting blood glucose were measured in each group,and the levels of LPS in serum were assessed using ELISA.Western blotting was used to evaluate the expression of Myeloid differentiation primary response protein 88(MyD88),p65,p-IkB,p-p65 in colonic tissue.Real-time PCR was employed to determine the expression levels of IL-1βmRNA,TNF-αmRNA and IL-18 mRNA in colonic tissue.The pathological morphology of liver and colon were observed by hematoxylin-eosin(HE)staining.Results:Compared with control group,the body weight and blood pressure of rats increased in model group(P<0.05).The level of TC,TG,LDL-C and FBG increased in model group(P<0.05),while level of HDL-C decreased in model group(P<0.05).The level of LPS in serum increased in model group(P<0.01).Compared with control group,the expressions of MyD88,p-IκB,p-p65 and p65 in colon tissue increas

关 键 词：肥胖相关性高血压 痰瘀互结证 晕清降压方 替米沙坦 NF-ΚB信号通路 肠道炎症 大鼠 

分 类 号：R285.5[医药卫生—中药学]