藤黄酸对心肌梗死大鼠心功能的影响及其机制

Effects of garcinoic acid on cardiac function and its mechanism in post-myocardial infarction rats

目的:探讨藤黄酸(GA)对心肌梗死(心梗)大鼠心功能的影响及可能机制。方法:SD雄性大鼠,随机分为正常对照组(Control)、心梗组(MI+vehicle)、心梗+藤黄酸组(MI+GA)。人脐静脉内皮细胞(HUVECs)分别培养在装有GA和vehicle的培养皿中。2周后行超声检测左心室舒张末期直径,左心射血分数,心室缩短分数;ELISA法检测血清脑利钠肽(BNP)水平;CCK-8检测细胞活性;免疫荧光法检测α-SMA(平滑肌标记物),ki67和CD31(内皮细胞标记物)的表达水平;Western印记分析缺氧诱导因子-1(HIF-1α),血管上皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)在心肌和HUVECs中的表达水平。结果:MI+vehicle组大鼠左室舒张末期直径增大,左心射血分数及心室缩短分数降低,GA干预能改善大鼠心功能;MI+vehicle组大鼠心肌梗死周边区血管密度明显降低,GA干预显著上调α-SMA、CD31、Ki67的表达,促进新生血管生成;在缺氧条件下,GA显著增强HUVECs成管能力。此外,GA可增加促血管生成因子HIF-1α、VEGF-A和bFGF的表达。结论:GA可能通过促进新血管形成而改善心梗后大鼠的心脏功能。

Objective: To investigate the effects of Garcinoic acid(GA)on cardiac function in post myocar-dial infarction(MI) rats and its possible mechanism.Methods: SD rats were randomized into sham group, MI+vehicle group, and MI+GA group in vivo. Human umbilical endothelial cells(HU-VECs) were cultured in vehicle or GA, and then additionally 2% hypoxia in vitro. Left ventricular end-diastolic diameter, left ventricular ejection fraction, and ventricular shortening were detected after2 weeks;Serum BNP levels was detected by ELISA. The cell viability was evaluated by the Cell Counting kit(CCK-8) assay. Immunofluorescence was adopted to detect the expression levels ofα-SMA(Smooth muscle marker), ki67, and CD31(Endothelial cell marker). Western Blot was used to detect the level of HIF-1α, VEGF, and bFGF expression in myocardium and HUVECs.Results:In the MI+vehicle group, the left ventricular end-diastolic diameter increased, left ventricular ejec-tion fraction and ventricular shortening score decreased, and GA intervention improved cardiac func-tion in rats. In the MI+vehicle group, the vascular density in the peripheral region of myocardial in-farction was significantly decreased. GA intervention significantly up-regulated the expression ofα-SMA, CD31, and Ki67, and promoted angiogenesis. Moreover, GA significantly enhanced tube formation in HUVECs under hypoxia condition, and increased the expression of pro-angiogenic fac-tors HIF-1α, VEGF-A, and bFGF.Conclusion: GA may improve cardiac function in rats after myo-cardial infarction by promoting neovascularization.