摘要
目的基于NF-κB信号通路探讨莲心碱对高脂饮食诱导高血压小鼠血管炎症的影响。方法采用随机数字表法将30只雄性C57BL/6小鼠分为对照组6只以普通饲料喂养,其余24只作为造模组以高脂饲料喂养。喂养6周后,当造模组小鼠体质量超过对照组小鼠体质量的20%时,同时收缩压>120 mm Hg,视为代谢性高血压模型造模成功。将造模成功的12只小鼠按随机数字表法分为模型组和干预组各6只。造模成功后第2天,干预组按体质量5 mg/(kg·d)腹腔注射莲心碱溶液,对照组和模型组按体质量0.15 mL/(kg·d)腹腔注射生理盐水,每3 d注射1次,均连续干预12周。干预期间模型组和干预组均持续喂养高脂饲料。在实验过程中,每周固定时间称量小鼠体质量并记录,每2周用无创鼠尾血压仪测量小鼠收缩压(SBP)、舒张压(DBP)和平均动脉压(MAP)。干预结束取眼底静脉血和腹主动脉组织,检测3组血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)含量;HE染色观察腹主动脉组织病理形态,并测量腹主动脉血管壁厚度;免疫组化法检测腹主动脉组织白介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、IL-6、核因子-κB p65亚基(p65)、磷酸化p65(p-p65)、人核因子κB抑制蛋白(IκB)、磷酸化IκB(p-IκB)蛋白表达水平。结果HE染色结果显示:对照组腹主动脉组织结构完整,未见病理改变;模型组腹主动脉血管中弹性纤维排列紊乱、断裂;干预组腹主动脉血管中弹性纤维排列有序而完整。与对照组比较,模型组第2周开始体质量、SBP均明显升高(P<0.05),第4周开始DBP、MAP均明显升高(P<0.05);干预后模型组腹主动脉血管壁厚度明显增加(P<0.05),腹主动脉组织IL-1β、TNF-α、IL-6阳性表达率均明显升高(P<0.05),腹主动脉组织p-p65/p65、p-IκB/IκB均明显升高(P<0.05)。与模型组比较,干预组第8周开始SBP、MAP均明显降低(P<0.05),第9周开始体质量明显降低(P<0.05),第10周开始DBP明显降低(P<0.05);干预后干预组腹主动脉血管壁厚度明显减少(P<0.05),腹主动脉组织IL-1β、TNF-α、IL-6阳性表达率均明显降低(P<0.05),腹主动脉组织p-p65/p65、p-IκB/IκB均明显降低(P<0.05)。结论莲心碱能够降低高脂饮食诱导的代谢性高血压小鼠血压,改善血管炎症,其机制可能通过NF-κB信号通路发挥作用。
Objective:To investigate the effect of liensinine on vascular inflammation in high-fat diet-induced hypertensive mice based on NF-κB signaling pathway.Methods:Thirty male C57BL/6 mice were divided into control group of 6 mice fed with regular diet,and the remaining 24 mice were used as modeling group fed with high-fat diet,using a random number table method.After 6 weeks of feeding,when the body weight of the modeling group exceeded that of the control group by 20%and systolic blood pressure(SBP)was greater than 120 mm Hg,the metabolic hypertension model was considered successfully established.Twelve successfully modeled mice were randomly divided into model group and intervention group,with 6 mice in each group.On the second day after successful modeling,the intervention group was intraperitoneally injected with 5 mg/(kg·d)of liensinine,while the control and model groups were intraperitoneally injected with 0.15 mL/(kg·d)of physiological saline,once every 3 days,for 12 consecutive weeks of intervention.During the intervention period,the model and intervention groups were continuously fed high-fat diet.During the experiment,the body weight of mice was measured and recorded weekly,and the systolic blood pressure(SBP),diastolic blood pressure(DBP),and mean arterial pressure(MAP)of mice were measured every 2 weeks using a non-invasive tail blood pressure monitor.At the end of the intervention,retinal venous blood and abdominal aortic tissue were collected.The levels of serum total cholesterol(TC),triglycerides(TG),and low-density lipoprotein cholesterol(LDL-C)were detected.HE staining was used to observe the pathological morphology of the abdominal aorta tissue,and the thickness of the abdominal aorta vascular wall was measured.Immunohistochemistry was used to detect the protein expression levels of interleukin(IL)-1β,tumor necrosis factor-α(TNF-α),IL-6,nuclear factor-κB p65(p65),phosphorylated p65(p-p65),inhibitor of nuclear factor-κB(IκB),and phosphorylated IκB(p-IκB)in abdominal aortic tissue.Results:The HE staining results showed that the control group had intact abdominal aortic tissue structure and no pathological changes were observed;the elastic fibers in the abdominal aortic vessels of the model group were disordered arrangement and broken;the elastic fibers in the abdominal aortic vessels of the intervention group were well-organized and intact.Compared with the control group,the body weight and SBP of the model group increased significantly from the second week(P<0.05),and DBP and MAP increased significantly from the fourth week(P<0.05);after intervention,the thickness of the abdominal aorta vascular wall increased significantly(P<0.05),and the positive expression rates of IL-1β,TNF-α,IL-6 and the ratios of p-p65/p65 and p-IκB/IκB in the abdominal aortic tissue increased significantly(P<0.05).Compared with the model group,the intervention group showed a significant decrease in SBP and MAP from the eighth week(P<0.05),a significant decrease in body weight from the ninth week(P<0.05),and a significant decrease in DBP from the tenth week(P<0.05);after intervention,the thickness of the abdominal aorta vascular wall reduced significantly(P<0.05),and the positive expression rates of IL-1β,TNF-α,IL-6 and the ratios of p-p65/p65 and p-IκB/IκB in the abdominal aortic tissue reduced significantly(P<0.05).Conclusion:Liensinine can reduce blood pressure and improve vascular inflammation in metabolic hypertensive mice induced by high-fat diet,and its mechanism may be through the NF-κB signaling pathway.
作者
姚琳
胡俊灵
郑梦婷
任晨曦
赵小雪
陈达鑫
林珊
YAO Lin;HU Junling;ZHENG Mengting;REN Chenxi;ZHAO Xiaoxue;CHEN Daxin;LIN Shan(Academy of Integrative Medicine,College of Integrative Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou,Fujian 350122,China;Fujian Key Laboratory of Integrative Medicine on Geriatrics,Fuzhou,Fujian 350122,China;Fujian Collaborative Innovation Center for Integrative Medicine in Prevention and Treatment of Major Chronic Cardiovascular Diseases,Fuzhou,Fujian 350122,China)
出处
《福建中医药》
2025年第5期31-37,共7页
Fujian Journal of Traditional Chinese Medicine
基金
福建省自然科学基金项目(2022J01369)
福建省高校产学合作项目(2024Y4009)
福建中医药大学校管课题(X2024036)。
