摘要
目的:观察淫羊藿苷(ICA)通过一氧化氮(NO)-环磷酸鸟苷(cGMP)-蛋白激酶G(PKG)通路对射血分数保留型心衰(HFPEF)大鼠心室重塑的影响。方法:建立醋酸脱氧皮质酮(DOCA)敏感型HFPEF大鼠模型,造模成功后,随机分成Model组、ICA低、中、高剂量组、抑制剂组,随机选取12只大鼠作为control组,各组灌胃相应药物,每天1次,连续6周。超声心动图检测大鼠心功能;心导管法测定血流动力学参数;HE染色观察大鼠心肌组织病理损伤;试剂盒检测NO、cGMP、活性氧(ROS)、白细胞介素(IL)-6、IL-1β、肿瘤坏死因子(TNF)-α水平;免疫荧光染色观察血小板-内皮细胞黏附分子-1(CD31)表达;Western blot检测PKG、内皮型一氧化氮合成酶(eNOS)、诱导性一氧化氮合酶(iNOS)、可溶性鸟苷酸环化酶α(sGCα)蛋白表达。结果:与control组比较,Model组大鼠左室射血分数(LVEF)、左心室缩短分数(LVFS)、二尖瓣舒张早期/舒张晚期血流速度最大峰值(E/A)、左心室收缩压(LVSP)、左室压力最大上升速率(+dp/dt max)、左室压力最大下降速率(-dp/dt max)、NO、cGMP水平、CD31及PKG、eNOS、sGCα蛋白表达水平降低(P<0.05),左心室前壁厚度(LVAM)、左心室后壁厚度(LVPW)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室舒张末期压力(LVEDP)、ROS、IL-6、IL-1β、TNF-α水平、iNOS蛋白表达水平升高(P<0.05)。与Model组比较,ICA低、中、高剂量组大鼠LVEF、LVFS、E/A、LVSP、+dp/dt max、-dp/dt max、NO、cGMP水平、CD31及PKG、eNOS、sGCα蛋白表达水平升高(P<0.05),LVAM、LVPW、LVEDD、LVESD、LVEDP、ROS、IL-6、IL-1β、TNF-α水平、iNOS蛋白表达水平降低(P<0.05),其中ICA高剂量组变化更显著(P<0.05)。与ICA高剂量组比较,抑制剂组大鼠LVEF、LVFS、E/A、LVSP、+dp/dt max、-dp/dt max、NO、cGMP水平、CD31及PKG、eNOS、sGCα蛋白表达水平降低(P<0.05),LVAM、LVPW、LVEDD、LVESD、LVEDP、ROS、IL-6、IL-1β、TNF-α水平�
Objective:To observe the effects of Icariin(ICA)on ventricular remodeling in rats with heart failure with preserved ejection fraction(HFPEF)through nitric oxide(NO)-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)pathway.Methods:Deoxycorticosterone acetate(DOCA)-sensitive HFPEF rat models of were established,and were randomly divided into the model group,the low-dose,medium-dose and high-dose of ICA groups,and the inhibitor group;a total of 12 rats were randomly selected as the control group.Each group was given the gastric irrigation with corresponding medicines once a day for 6 weeks.The heart function of rats was detected by echocardiography;hemodynamic parameters were measured by cardiac catheterization procedure;the pathological injury of myocardium was observed by HE staining;the levels of NO,cGMP,reactive oxygen species(ROS),interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-αwere detected by reagent kit;the expressions of plateletendothelial cell adhesion molecule-1(CD31)were observed by immunofluorescence staining;the expressions of PKG,endothelial nitric oxide synthase(eNOS),inducable nitric oxide synthase(iNOS),and soluble guanylate cyclaseα(sGCα)were detected by Western blot.Results:When compared with those in the control group,the levels of LVEF,LVFS,E/A,LVSP,+dp/dt max,-dp/dt max,NO,and cGMP,CD31,and the protein expression levels of PKG,eNOS and sGCαin the model group were decreased(P<0.05);the levels of LVAM,LVPW,LVEDD,LVESD,LVEDP,ROS,IL-6,IL-1β,and TNF-α,and iNOS protein expression levels in the model group were increased(P<0.05).When compared with those in the model group,the levels of LVEF,LVFS,E/A,LVSP,+dp/dt max,-dp/dt max,NO,and cGMP,CD31,and the protein expression levels of PKG,eNOS and sGCαin the low-dose,medium-dose and high-dose of ICA groups were increased(P<0.05);the levels of LVAM,LVPW,LVEDD,LVESD,LVEDP,ROS,IL-6,IL-1β,and TNF-α,and iNOS protein expression level in the low-dose,mediumdose and high-dose of ICA groups were decreased(P<0.05);the changes were more si
作者
陈丽珍
杨雷
许锦文
CHEN Lizhen;YANG Lei;XU Jinwen(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;The Second Department of Internal Medicine,Pujiang County Hospital of Chinese Medicine,Pujiang Zhejiang 322200,China)
出处
《新中医》
CAS
2024年第3期209-216,共8页
New Chinese Medicine
