丹参酚酸B调控PKD1-HIF-1α-VEGF通路促心肌梗死大鼠血管新生的作用  

Angiogenesis promotion function of salvianolic acid Bin rats with myocardial infarction via PKD1-HIF-1α-VEGF pathway

作　　者：刘暖[1] 杨雷[1] 毛秉豫[1] LIU Nuan;YANG Lei;MAO Bing-yu(Henan Key Lab of Zhang ZhongJing Formulae and Herbs for Immunoregulation,Nanyang Institute of Technology,Nanyang Henan 473004,China)

机构地区：[1]南阳理工学院河南省张仲景方药与免疫调节重点实验室,河南南阳473004

出　　处：《中国药理学通报》2020年第7期984-990,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.81873106);河南省高等学校重点研究项目(No.19A360030,18B360011)。

摘　　要：目的探讨丹参酚酸B(SAB)是否通过调控蛋白激酶D1(PKD1)、缺氧诱导因子(HIF)-1α和血管内皮生长因子(VEGF)的表达而促心肌梗死大鼠血管新生。方法 40只♂Wistar大鼠被随机分为假手术(Sham)、心梗模型(MI)、SAB和CID755673阻断剂(CID)组。应用HE、Masson和透射电镜染色分析心肌组织和血管的形态学变化,免疫荧光、免疫组化和免疫印迹染色分析心肌组织中PKD1、HIF-1α、VEGF和Ⅷ蛋白的表达。结果 SAB用药可以减少MI大鼠的肉芽组织和瘢痕组织,降低心肌的胶原占比,使缺血受损引发的心肌纹理模糊、闰盘断裂、线粒体萎缩、微血管管腔塌陷恢复为结构清晰完整的心肌纹理、闰盘和微血管管腔及饱满的线粒体结构;并可以上调心肌组织中PKD1、HIF-1α、VEGF和Ⅷ因子蛋白的表达。注射CID后SAB的作用被明显抑制。结论 SAB可能通过调控PKD1-HIF-1α-VEGF通路而促心肌梗死大鼠损伤后心肌组织的血管新生。Aim To investigate the angiogenesis effects of salvianolic acid B(SAB)on the expression of protein kinase D1(PKD1),hypoxia inducible factor-1α(HIF-1α)and vascular endothelial growth factor(VEGF)in rats with myocardial infarction.Methods Forty male Wistar rats were randomly divided into four groups:sham operation group(sham),MI group(MI),SAB group and CID 755673 blocker group(CID).The morphological changes of myocardium and blood vessel were analyzed by HE staining,Masson staining and transmission electron microscopy(TEM).The expressions of PKD1,HIF-1α,VEGF andⅧin myocardium were analyzed by immunofluorescence,immunohistochemistry and Western blot.Results SAB could reduce the granulation and scar tissue of MI rats,decrease the proportion of collagen in myocardium,recover the fuzzy myocardial texture,leap disc fracture,mitochondrial atrophy and microvascular lumen collapse caused by ischemia damage to clear and complete myocardial texture,leap disc,microvascular lumen and full mitochondrial structure.Moreover,SAB could up-regulate the expression of PKD1,HIF-1α,VEGF and factorⅧin myocardium.Conclusion SAB might promote the angiogenesis of myocardial tissue in rats with myocardial infarction through the regulation of PKD1-HIF-1α-VEGF signaling pathway.

关 键 词：丹参酚酸B 蛋白激酶D1 缺氧诱导因子-1Α 血管内皮生长因子 心肌梗死 心肌缺血 

分 类 号：R-332[医药卫生] R284.1