摘要
目的 探讨黄芩汤通过调控NEK7-NLRP3/IL-1β炎症轴改善肥胖高血压大鼠管周脂肪炎性微环境,保护血管内皮功能。方法 选取4周龄雄性Wistar大鼠50只,随机选取10只为对照组,另40只喂高盐高脂饲料构建肥胖高血压模型,造模成功的大鼠(20只)随机分为模型组,黄芩汤正常剂量组、高剂量组和IL-1β抑制剂组,每组5只。中药治疗组从第12周起,正常剂量组灌胃黄芩汤2.835 g·kg^(-1),高剂量组灌胃5.67 g·kg^(-1),IL-1β抑制剂组腹腔注射1.5 mg·kg^(-1) AS101,每周3次,干预8周。末次给药12 h后称质量并采血,分离胸主动脉及管周脂肪组织。检测血清炎症因子含量,观察病理变化,免疫荧光检测eNOS表达,Western blot和qPCR检测NEK7、NLRP3、Caspase-1、ASC、IL-1β的表达。结果 模型组大鼠体质量显著增加,管周脂肪脂滴面积增大,内皮损伤严重;模型组收缩压、舒张压,血清IL-1β、IL-6和TNF-α显著升高,eNOS表达显著降低,NEK7、NLRP3、Caspase-1、ASC和IL-1β蛋白及mRNA表达水平显著升高。与模型组相比,黄芩汤和IL-1β抑制剂组大鼠体质量降低,内皮损伤减轻,收缩压和舒张压降低,血清IL-1β、IL-6和TNF-α降低,eNOS表达升高。黄芩汤高剂量组和IL-1β抑制剂组NEK7、NLRP3、Caspase-1、ASC和IL-1β蛋白表达显著降低。另外,黄芩汤可保护肥胖高血压血管内皮功能,其中高剂量组效果较为明显。结论 黄芩汤能通过调节NEK7-NLRP3/IL-1β炎症轴,改善血管周围脂肪炎性微环境,保护肥胖高血压大鼠的血管内皮功能。
OBJECTIVE To explore the effect of Huangqin decoction on improving peritubular fat inflammatory microenvironment and protecting vascular endothelial function in obese hypertensive rats by regulating the NEK7-NLRP3/IL-1βinflammatory axis.METHODS Fifty 4-week-old male Wistar rats were selected,10 of which were randomly selected as the control group,and the other 40 were fed a high-salt and high-fat diet to establish an obese hypertension model.The rats with successful modeling(20 rats)were randomly divided into the model group,normal-dose Huangqin decoction group,high-dose Huangqin decoction group,and IL-1βinhibitor group,with 5 rats in each group.From the 12th week,the normal-dose group was gavaged with Huangqin decoction 2.835 g·kg^(-1),the high-dose group was gavaged with Huangqin decoction 5.67 g·kg^(-1),and the IL-1βinhibitor group was intraperitoneally injected with 1.5 mg·kg^(-1) AS101,3 times a week,for 8 weeks.The rats were weighed and blood was collected 12 h after the last administration,and the thoracic aorta and perivascular fat tissue were isolated.Serum inflammatory factors were detected,pathological changes were observed,eNOS expression was detected by immunofluorescence,and NEK7,NLRP3,Caspase-1,ASC,and IL-1βexpression levels were detected by Western blot and qPCR.RESULTS The rats in the model group had a significant increase in body weight,an increase in the area of peritubular fat lipid droplets,and severe endothelial injury;systolic blood pressure,diastolic blood pressure,serum IL-1β,IL-6,and TNF-αwere significantly elevated in the model group,and the expression of eNOS was significantly reduced,and the expression levels of NEK7,NLRP3,Caspase-1,ASC,and IL-1βproteins and mRNAs were significantly elevated.Compared with the model group,rats in the Huangqin decoction and IL-1βinhibitor groups had lower body weights,reduced endothelial damage,lower systolic and diastolic blood pressures,lower serum IL-1β,IL-6,and TNF-α,and higher eNOS expression.NEK7,NLRP3,Caspase-1,ASC and IL-1βprotein expression was significantly reduced in the high dose group of Huangqin decoction and the IL-1βinhibitor group.In addition,Huangqin decoction protected the endothelial function of obese hypertensive vessels in a dose-dependent manner,with the effect being more pronounced in the high-dose group.CONCLUSION Huangqin decoction can improve the inflammatory microenvironment of perivascular fat and protect the vascular endothelial function in obese hypertension by regulating the NEK7-NLRP3/IL-1βinflammatory axis.
作者
刘旋
赵福森
徐启耀
张蒙
郭灿
陈兆阳
沈建平
王新东
LIU Xuan;ZHAO Fusen;XU Qiyao;ZHANG Meng;GUO Can;CHEN Zhaoyang;SHEN Jianping;WANG Xindong(The Third Clinical Medical College,Nanjing University of Chinese Medicine,Nanjing 210028,China;Department of Cardiology,Jiangsu Province Hospital of Integrated Chinese and Western Medicine,Nanjing 210028,China)
出处
《南京中医药大学学报》
CAS
CSCD
北大核心
2024年第9期896-905,共10页
Journal of Nanjing University of Traditional Chinese Medicine
基金
江苏省自然科学基金面上项目(BK20211387)
江苏省研究生科研与实践创新计划项目(SJCX24_1055)。
