三七总皂苷通过Notch3/Hes-1/p27Kip1信号通路抑制低氧性肺动脉高压大鼠肺血管重构  

Panax notoginseng saponins inhibit pulmonary vascular remodeling in hypoxic pulmonary hypertensive rats via Notch3/Hes-1/p27;signaling pathway

作　　者：张赛[1] 宋正阳 王淑远 田云娜 王肖婷 林青青 王万铁[1] ZHANG Sai;SONG Zheng-yang;WANG Shu-yuan;TIAN Yun-na;WANG Xiao-ting;LIN Qing-qing;WANG Wan-tie(Department of Physiology and Pathophysiology,Wenzhou Medical University,Wenzhou 325035,China)

机构地区：[1]温州医科大学生理学与病理生理学系,浙江温州325035

出　　处：《中国病理生理杂志》2022年第2期209-214,共6页Chinese Journal of Pathophysiology

基　　金：浙江省介入肺脏病重点实验室建设项目(No.2019E10014)。

摘　　要：目的:探讨Notch3/Hes-1/p27;信号通路与低氧性肺动脉高压大鼠肺血管重构的关系及三七总皂苷(PNS)的干预作用。方法:将SPF级雄性SD大鼠采用随机编号分为3组:正常组(C组),低氧组(H组)和PNS组(P组),检测肺动脉压,称量右心室重量,HE染色和Masson染色观察肺血管重构情况,RT-qPCR检测大鼠肺组织中Notch3、Hes-1和p27;的mRNA表达水平,Western blot检测大鼠肺组织中Notch3、Hes-1、p27^(Kipl),增殖细胞核抗原(PCNA)和caspase-3的蛋白水平。结果:与C组相比,H组大鼠的肺动脉压和右心室肥厚指数明显增加;肺血管重构现象明显;Notch3、Hes-1和PCNA的蛋白水平增加,p27;和caspase-3的蛋白水平降低;Notch3和Hes-1的mRNA表达增加,p27;的mRNA表达降低(P<0.05)。经PNS干预后,与H组相比,P组大鼠的肺动脉压和右心室肥厚指数降低;肺血管重构现象改善;Notch3、Hes-1和PCNA的蛋白水平降低,p27;和caspase-3的蛋白水平增加;Notch3和Hes-1的mRNA表达降低,p27;的mRNA表达增加(P<0.05)。结论:PNS可通过抑制Notch3/Hes-1/p27;信号通路,减少低氧诱导的肺动脉高压大鼠肺血管重构。AIM:To explore the effects of Panax notoginseng saponin(PNS)on hypoxia pulmonary hypertension(HPH)-induced pulmonary vascular remodeling in rats.METHODS:Male SD rats were randomly divided into 3 groups:normoxic control group(C group),hypoxia group(H group)and PNS group(P group). Mean pulmonary artery pressure,right ventricular hypertrophy index and pulmonary vascular remodeling were detected. The protein levels of Notch3,Hes1,p27^(Kipl),proliferating cell nuclear antigen(PCNA)and caspase-3 were measured by Western blot. The mRNA expression levels of Notch3,Hes-1 and p27;were measured by RT-qPCR.RESULTS:Pulmonary hypertension,right rentricular hypertrophy and pulmonary vascular remodeling were observed in HPH model rats,with increased expression of Notch3,Hes-1 and PCNA,and decreased expression of p27;and caspase-3(P<0. 05). Furthermore,PNS treatment alleviated pulmonary hypertension and right rentricular hypertrophy,and inhibited hypoxia-induced pulmonary vascular remodeling. Treatment with PNS also inhibited the expresion of Notch3,Hes-1 and PCNA,and stimulated the expresion of p27;and caspase-3(P<0. 05).CONCLUSION:Treatment with PNS attenuates HPH pulmonary vascular remodeling in rats by inhibition of Notch3/Hes-1/p27;signaling pathway.

关 键 词：肺动脉高压 低氧 三七总皂苷 Notch3/Hes-1/p27 信号通路 血管重构 

分 类 号：R543.2[医药卫生—心血管疾病] R363.2[医药卫生—内科学]