低剂量参麦方调控HIF-1/VEGF信号通路对心力衰竭大鼠的改善作用  

The improvement effect of low-dose Shenmai Recipe on heart failure rats by regulating HIF-1/VEGF signaling pathway

作　　者：王喆 郭流漓 刘祎曼 庄朋伟[1] 任明[1,2] WANG Zhe;GUO Liuli;LIU Yiman;ZHUANG Pengwei;REN Ming(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Tianjin University of Traditional Chinese Medicine Baokang Hospital,Tianjin 300193,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津中医药大学附属保康医院,天津300193

出　　处：《天津中医药大学学报》2024年第10期900-906,共7页Journal of Tianjin University of Traditional Chinese Medicine

基　　金：国家重点研发计划项目(2018YFC1707403)。

摘　　要：[目的]探究参麦方对心力衰竭(HF)大鼠血管生成的改善作用以及对缺氧诱导因子-1(HIF-1)/血管内皮生长因子(VEGF)信号通路的影响。[方法]选取55只SPF级雄性SD大鼠,采用腹腔注射盐酸多柔比星构建HF模型,随机分为正常组、模型组、参麦高剂量组和参麦低剂量组。其中正常组10只,其余各组均15只,实验时间为8周。实验结束后,检测心功能指标及苏木精-伊红(HE)染色、马松(Masson)病理染色、免疫组织化学CD31染色;酶联免疫吸附(ELISA)试剂盒检测血清中N端前脑钠肽(NT-proBNP)、内皮素-1(ET-1)含量;硝酸还原酶法检测血清中一氧化氮(NO)水平;实时荧光定量聚合酶链式反应(RT-qPCR)检测白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、血管细胞黏附分子-1(VCAM-1)、缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子A(VEGFA)mRNA水平;蛋白免疫印迹(Western Blot)法检测HIF-1α和VEGFA蛋白表达量。[结果]各组大鼠心功能指标、NT-proBNP、ET-1、NO、HE染色及CD31染色结果提示给药组较模型组改善明显,且低剂量组整体改善较为显著。RT-qPCR结果显示,给药组IL-6、IL-1β、TNF-α、VCAM-1表达水平较模型组下降(P<0.05或P<0.01),HIF-1α、VEGFA表达水平上升(P<0.05)。Western Blot结果提示给药组HIF-1α、VEGFA蛋白表达情况较模型组改善(P<0.05),且低剂量组较模型组上调明显(P<0.05)。[结论]参麦方可能通过调控HIF-1/VEGF信号通路,降低炎症反应,促进血管新生,改善HF大鼠心功能。[Objective]To explore the effect of Shenmai Recipe on angiogenesis in rats with heart failure and its effect on HIF-1/VEGF signaling pathway.[Methods]Total 55 SPF male SD rats were selected to construct HF model by intraperitoneal injection of doxorubicin hydrochloride.They were randomly divided into normal group,model group,Shenmai high-dose group and Shenmai low-dose group.There were 10 rats in the normal group and 15 rats in the other groups for 8 weeks.At the end of the experiment,cardiac function indexes were observed,and hematoxylin-eosin staining(HE),Masson pathological staining and immunohistochemical CD31 staining were performed;the levels of N-terminal pro-brain natriuretic peptide(NT-proBNP)and endothelin(ET-1)in serum were detected by ELISA kit.The level of nitric oxide(NO)in serum was detected by nitrate reductase method.The mRNA levels of interleukin-6(IL-6),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),vascular cell adhesion molecule-1(VCAM-1),hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGFA)were detected by RT-qPCR.Western Blot was used to detect the expression of HIF-1αand VEGFA protein.[Results]The results of cardiac function index,NT-proBNP,ET-1,NO,HE pathological staining and CD31 staining showed that the treatment group was significantly improved compared with the model group,and the overall improvement of the low-dose group was more obvious.The results of RT-qPCR showed that the expression levels of IL-6,IL-1β,TNF-αand VCAM-1 in the administration group were significantly lower than those in the model group(P<0.05 or P<0.01),and the expression levels of HIF-1αand VEGFA were significantly increased(P<0.05).Western Blot results showed that the expression of HIF-1αand VEGFA protein in the administration group was significantly improved compared with the model group(P<0.05),and the low-dose group was significantly up-regulated compared with the model group(P<0.05).[Conclusion]Shenmai Recipe may reduce inflammation,promote angiogenesis and improv

关 键 词：参麦方 心力衰竭 缺氧诱导因子-1/血管内皮生长因子信号通路 血管新生 

分 类 号：R285.5[医药卫生—中药学]