基于核因子κB通路探究培补二天膏对肾脏的保护作用机制OA
Exploring the protective mechanism of Peibu Ertian Paste on kidneys based on the NF-κB pathway
目的 基于核因子κB(nuclear factor-kappa B,NF-κB)通路研究培补二天膏对自发性高血压大鼠(spontaneously hypertensive rats,SHR)肾脏保护作用,为该膏方的临床治疗提供科学依据.方法 选用10 只正常血压WKY大鼠作为空白组,将50 只SHR大鼠随机分为模型组、厄贝沙坦组[10.13 mg/(kg·d)]和膏方低、中、高剂量组[0.58、1.15、3.46 g/(kg·d)],干预 4 周后采用非侵入性的尾套法检测尾动脉压,苏木精—伊红染色法观察肾脏病理切片,免疫组织化学染色法观察炎性因子白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)表达水平及蛋白质免疫印迹(western blot,WB)法观察NF-κB通路关键蛋白κB抑制蛋白α(inhibitor of kappa B alpha,IκBα)、核转录因子p65 亚基(nuclear factor p65 subunit,p65)表达水平.结果 干预 4 周后,与模型组相比,膏方高剂量组大鼠血压明显下降(P<0.01),肾小球硬化及炎性浸润显著改善,IκBα降解减少(P<0.01),p65 核转位降低(P<0.01),下游炎性因子IL-6、IL-1β、TNF-α 表达水平降低(P<0.01),其作用强度与厄贝沙坦组相当(P>0.05).结论 培补二天膏对SHR大鼠肾脏的保护作用的机制可能是通过抑制NF-κB通路的活化、减少IκBα降解和p65 核转位,从而下调IL-6、IL-1β及TNF-α等炎症因子表达,最终达到改善高血压肾损害的炎症微环境的目的.
Objective To investigate the renal protective effect of Peibu Ertian Paste on spontaneously hypertensive rats(SHR)based on the nuclear factor-kappa B(NF-κB)pathway,and to provide a scientific basis for the clinical application of this paste formulation.Methods Ten normotensive Wistar-Kyoto(WKY)rats were selected as the control group.Fifty SHR rats were randomly divided into the model group,the irbesartan group[10.13 mg/(kg·d)],and the low dose group,the medium dose group and the high dose group[0.58,1.15,3.46 g/(kg·d)].After 4 weeks of intervention,tail artery pressure was measured using the non-invasive tail-cuff method.Renal pathological changes were observed via hematoxylin-eosin(HE)staining.The expression levels of inflammatory factors interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α)were detected by immunohistochemical staining.The expression levels of key NF-κB pathway proteins,inhibitor of kappa B(IκB)and the nuclear factor p65 subunit(p65),were assessed by western blot.Results After 4 weeks of intervention,compared with the model group,the high-dose Paste group showed a significant decrease in blood pressure(P<0.01),significant improvements in glomerulosclerosis and inflammatory infiltration,reduced IκBα degradation(P<0.01),decreased p65 nuclear translocation(P<0.01),and lowered expression levels of the downstream inflammatory factors IL-6,IL-1β,and TNF-α(P<0.01).The potency of these effects was compared with that in the irbesartan group(P>0.05).Conclusion Peibu Ertian Paste exerts a renal protective effect in SHR rats.The mechanism may involve inhibiting the activation of the NF-κB pathway,reducing IκB degradation and p65 nuclear translocation,thereby down-regulating the expression of inflammatory factors such as IL-6,IL-1β,and TNF-α,and ultimately ameliorating the inflammatory micro-environment in hypertensive renal damage.
余德华;施佳;包涵;陈竞纬
215000 南京中医药大学附属苏州市中医医院心内科215000 南京中医药大学附属苏州市中医医院心内科南京中医药大学中医学院215000 南京中医药大学附属苏州市中医医院心内科
医药卫生
自发性高血压大鼠高血压肾损害核因子κB通路炎性因子培补二天膏
spontaneously hypertensive rathypertensive renal damagenuclear factor-kappa B(NF-κB)pathwayinflammatory factorsPeibu Ertian Paste
《环球中医药》 2026 (2)
232-240,9
国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202007)全国名老中医岐黄学者史大卓工作室专项项目(苏卫健中医便函[2023]87号)2024年度江苏省中医学会振兴发展项目(ZXFZ2024062)新型临床诊疗技术及公共卫生重点项目(SKYD2022038)2024年度苏州市"科教强卫"重点项目(ZDXM2024013)
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