茯苓酸调节IL-6/JAK2/STAT3信号通路对原发性高血压 大鼠内皮细胞损伤的影响  

Effect of Pachymic Acid on Endothelial Cell Damage in Essential Hypertension Rats by Regulating the IL-6/JAK2/STAT3 Signaling Pathway

作　　者：高秀荣[1] 仝兴瑞 王庆海[1] 尹广利[1] 于文浩 GAO Xiurong;TONG Xingrui;WANG Qinghai(East Branch of Cangzhou Hospital of Integrated TCM-WM HEBEI,Hebei Cangzhou 061001,China)

机构地区：[1]河北省沧州中西医结合医院,河北沧州061001

出　　处：《河北医学》2024年第12期1987-1993,共7页Hebei Medicine

基　　金：河北省中医药管理局科研计划项目,(编号:2024464)。

摘　　要：目的:探讨茯苓酸调节白细胞介素-6(IL-6)/酪氨酸激酶2(JAK2)/信号转导和转录激活因子3(STAT3)通路对原发性高血压(EHT)大鼠内皮细胞损伤的影响。方法:60只EHT大鼠随机分为EHT组、茯苓酸低浓度组、茯苓酸高浓度组、贝那普利组、茯苓酸高浓度+rrIL-6组,每组12只,另取12只WKY大鼠作为对照组,检测大鼠舒张压、收缩压、平均动脉压变化;ELISA检测血清中内皮素-1(ET-1)、细胞间黏附分子-1(ICAM-1)、血管性血友病因子(vWF)水平;HE染色检测胸主动脉病理。大鼠UVEC细胞分为Vitro-对照组、Vitro-EHT组、Vitro-茯苓酸低浓度组、Vitro-茯苓酸高浓度组、Vitro-贝那普利组、Vitro-茯苓酸高浓度+rrIL-6组,ELISA检测UVEC细胞上清中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-10、IL-1β水平;流式细胞术检测UVEC细胞凋亡;Western blot检测UVEC细胞中IL-6、p-STAT3、p-JAK2蛋白。结果:与对照组相比,EHT组胸主动脉内膜结构异常,有残缺或凸起,内膜与外膜分界模糊,舒张压、收缩压、平均动脉压及血清中ET-1、ICAM-1、vWF水平升高(P<0.05);与EHT组相比,茯苓酸低浓度组、茯苓酸高浓度组、贝那普利组大鼠胸主动脉病理损伤有所改善,舒张压、收缩压、平均动脉压及血清中ET-1、ICAM-1、vWF水平降低(P<0.05)。与Vitro-对照组相比,Vitro-EHT组UVEC细胞上清中TNF-α、IL-1β水平、UVEC细胞凋亡率及UVEC细胞中IL-6、p-STAT3、p-JAK2蛋白升高,IL-10水平降低(P<0.05);与Vitro-EHT组相比,Vitro-茯苓酸低浓度组、Vitro-茯苓酸高浓度组、Vitro-贝那普利组UVEC细胞上清中TNF-α、IL-1β水平、UVEC细胞凋亡率及UVEC细胞中IL-6、p-STAT3、p-JAK2蛋白降低,IL-10水平升高(P<0.05)。rrIL-6逆转了高浓度茯苓酸对EHT大鼠内皮损伤、AngⅡ诱导的UVEC细胞炎症及凋亡的抑制作用。结论:茯苓酸可能通过抑制IL-6/JAK2/STAT3通路抑制EHT大鼠内皮细胞损伤。Objective:To investigate the effect of pachymic acid(PA)on endothelial cell damage in essential hypertension(EHT)rats by regulating the interleukin-6(IL-6)/tyrosine kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods:Sixty EHT rats were randomly separated into EHT group,low,high concentration PA group,benazepril group,high concentration PA+rrIL-6 group,with 12 rats in each group.Additional 12 Wistar-Kyoto(WKY)rats were selected as the control group.The changes in diastolic blood pressure(DBP),systolic blood pressure(SBP),and mean arterial pressure(MAP)of rats were detected.Enzyme-linked immunosorbent assay(ELISA)was applied to detect levels of endothelin-1(ET-1),intercellular adhesion molecule-1(ICAM-1),and von Willebrand factor(vWF)in serum.The hematoxylin and eosin(H&E)staining was applied to detect the pathology of the thoracic aorta.Rat umbilical vein endothelial cells(UVECs)were separated into Vitro-control group,Vitro-EHT group,Vitro-low concentration PA group,Vitro-high concentration PA group,Vitro-Benazepril group,and Vitro-high concentration PA+rrIL-6 group.ELISA was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-10(IL-10),and IL-1βin the supernatant of UVECs.Flow cytometry was applied to detect UVECs apoptosis.Western blot was applied to detect the proteins levels of IL-6,p-STAT3,and p-JAK2 in UVECs.Results:Compared with the control group,the endometrial structure of the thoracic aorta in the EHT group was abnormal,with defects or protrusions,and the boundary between the endometrium and outer membrane was blurred,the levels of DBP,SBP,MAP,and serum ET-1,ICAM-1,and vWF were significantly increased(P<0.05).Compared with the EHT group,the pathological damage of the thoracic aorta in rats in the low,high concentration PA,and benazepril group was significantly improved,the levels of DBP,SBP,MAP,and serum ET-1,ICAM-1,and vWF were significantly decreased(P<0.05).Compared with the Vitro-control group,the levels of TNF-α,IL-1βin the supernatant

关 键 词：茯苓酸 原发性高血压 凋亡 炎症 内皮细胞 

分 类 号：R285.5[医药卫生—中药学]