无患子皂苷对自发性高血压大鼠血管内皮功能和NLRP3炎性小体的影响  

Effects of Sapindus saponin on vascular endothelial function and NLRP3 inflammasome in spontaneously hypertensive rats

作　　者：刘金林[1] 刘毅[1] 高磊 祝燕平[1] LIU Jin-lin;LIU Yi;GAO Lei;ZHU Yan-ping(Anqing Medical College,Anqing 246052,China)

机构地区：[1]安庆医药高等专科学校,安徽安庆246052

出　　处：《中成药》2024年第5期1508-1513,共6页Chinese Traditional Patent Medicine

基　　金：安徽省高校自然科学研究重点项目(KJ2019A123,KJ2020A08865)。

摘　　要：目的探讨无患子皂苷对自发性高血压大鼠血管内皮功能和核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体的影响。方法将6只WKY大鼠设为对照组,18只自发性高血压大鼠(SHR)分为模型组、无患子皂苷组和替米沙坦组,每组6只。对照组和模型组大鼠灌胃生理盐水,无患子皂苷组和替米沙坦组分别灌胃无患子皂苷(162 mg/kg)和替米沙坦(10 mg/kg),连续灌胃35 d。给药结束后测量各组大鼠尾动脉收缩压(SBP)和舒张压(DBP),免疫组化法检测胸主动脉内膜中血管性假血友病因子(vWF)表达,HE染色观察大鼠胸主动脉组织病理变化,ELISA法检测血清中半胱天冬氨酸蛋白酶1(caspase-1)和白细胞介素1β(IL-1β)水平,RT-qPCR和Western blot法检测主动脉组织中p38、NLRP3、caspase-1 mRNA和蛋白表达。结果与对照组比较,模型组大鼠尾动脉SBP和DBP、血清中caspase-1和IL-1β水平、胸主动脉中p38、NLRP3、caspase-1 mRNA和蛋白表达均升高(P<0.01),胸主动脉内膜中vWF阳性表达增多(P<0.01),主动脉内膜和外膜脱落严重,中膜增厚;与模型组比较,无患子皂苷组和替米沙坦组大鼠尾动脉SBP和DBP、血清中caspase-1和IL-1β水平、胸主动脉中p38、NLRP3、caspase-1 mRNA和蛋白表达均降低(P<0.05),胸主动脉内膜中vWF阳性表达减少(P<0.05),主动脉内外膜损伤减轻,中膜厚度也有所降低。结论无患子皂苷能够有效降低自发性高血压大鼠的血压,改善血管内皮功能障碍,抑制炎症反应,其机制可能与抑制NLRP3炎症通路的激活有关。AIM To investigate the effects of Sapindus saponin on vascular endothelial function and nucleotide binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome in spontaneously hypertensive rats.METHODS In contrast to the 6 WKY rats of the control group treated with normal saline,other 18 spontaneously hypertensive rats(SHR)were divided into the model group for normal saline treatment,the Sapindus saponin group and the telmisartan group for the corresponding treatment at concentration of 162 mg/kg and 10 mg/kg,respectively,for a 35-day programme,with 6 rats in each group.The rats had their expression of von Willebrand factor(vWF)in the intima of thoracic aorta detected by immunohistochemistry;their pathological changes of thoracic aorta observed by HE staining;their serum levels of cysteinyl aspartate specific proteinase 1(caspase-1)and interleukin 1β(IL-1β)detected by ELISA;and their mRNA and protein expressions of p38,NLRP3,and caspase-1 in aortic tissues detected by RT-qPCR and Western blot.RESULTS Compared with the control group,the model group displayed increased SBP and DBP levels in tail artery,serum caspase-1 and IL-1βlevels,and mRNA and protein expressions of p38,NLRP3 and caspase-1 in thoracic aorta(P<0.01);increased positive expression of vWF in the thoracic aortic intima(P<0.01),severe loss of aortic intima and adventitia,and thickening of the media.Compared with the model group,the Sapindus saponin and telmisartan groups shared decreased SBP and DBP levels in the tail artery,serum caspase-1 and IL-1βlevels,and the mRNA and protein expressions of p38,NLRP3 and caspase-1 in the thoracic aorta(P<0.05),reduced positive expression of vWF in the thoracic aortic intima(P<0.05),reduced damage of aortic inner and outer membrane and thickness of the media as well.CONCLUSION Sapindus saponin can effectively reduce the blood pressure,improve the vascular endothelial dysfunction and inhibit the inflammatory response in spontaneously hypertensive rats,and the mechanism may be related to the inhibi

关 键 词：无患子皂苷 高血压 血管内皮功能 NLRP3炎性小体 

分 类 号：R285.5[医药卫生—中药学]