黄芪甲甙改善扩张型心肌病小鼠左室重构与磷酸化p-38MAPK相关性的实验研究

Association of attenuating left ventricular remodeling in murine dilated cardiomyopathy with phosphorylation of p38MAPK after interference by astragaloside

目的:探讨黄芪甲甙对柯萨奇病毒B3(CVB3)扩张型心肌病(DCM)小鼠左室重构的影响及其可能的作用机制。方法:BALB/c小鼠腹腔无菌重复增量接种CVB3建立扩张型心肌病动物模型(n=30);感染CVB3的小鼠以黄芪甲甙(0.6mg.kg-1.d-1)灌胃作为扩张型心肌病+黄芪甲甙治疗组(n=20);同期腹腔无菌注射等容积不含病毒的EMEM液作为正常对照组(n=10)。用高频超声心动图测量左室大小及心功能指数,用ELISA技术检测血清I、III型前胶原端肽(PINP、PICP及PIIINP)浓度并计算PICP/PICN比值,苦味酸天狼猩红胶原特异染色和偏光显微镜显像,并辅以图像分析软件计算心肌胶原容积积分(CVF)和I型胶原的含量,分别应用RT-PCR和Western blotting技术检测心肌组织中Ⅰ、Ⅲ型胶原变化和磷酸化p38MAPK的表达。结果:黄芪甲甙显著提高DCM小鼠的生存率、有效地降低扩大的左室内径及增加心脏功能;组织学和血清学显示DCM小鼠心肌组织胶原沉积明显多于正常对照组,而这种增多的趋势可被黄芪甲甙明显抑制(P<0.01);DCM小鼠心肌磷酸化p38MAPK表达高于正常对照组,黄芪甲甙治疗后p38MAPK活性明显低于正常对照组(分别为P<0.01和P<0.05)。结论:黄芪甲甙改善CVB3感染后导致的扩张型心肌病左室重构可能与降低磷酸化p38MAPK活动密切相关。

AIM： To investigate the effects and mechanism of astragaloside （Astr） on ventricular remodeling in CVB3 -induced murine dilated cardiomyopathy（DCM）. METHODS： BALB/c mice were inoculated ip repeatedly with CVB3 by increment to establish animal model of DCM （n =30）. Other mice infected with CVB3 were fed with Astra（0. 6 mg·kg^-1·d^-1 ） as DCM ＋ Astr （ n = 20）. Control mice （ n = 10） were treated with same volume of EMEM without CVB3. The diameter of LV and cardiac function were measured by high frequency echocardiography. Serum concentrations of PINP, PICP and PIIINP were detected by enzyme linked immunosorbent assay （ELISA）. The collagen in myocardium was stained with Sirius red. collagen volume fraction（CVF） and collagen I were calculated by image analysis software. Expressions of collagen type Ⅰ and Ⅲ were confirmed by reversed transcriptional pelymerase chain reaction （ RT - PCR）. The action of phosphorylation of p38MAPK was determined by Western blotting. RESULTS： Astragaloside raised the survival rates of mice with DCM, decreased LV dilation and dysfunction. Compared with controls, the exceptional deposition of collagens in DCM was suppressed by Astr. High expression of p38MAPK phosphorylation in DCM mice was decreased by Astr. CONCLUSION： Astr attenuating ventricular remodehng may be associated with the decreased action of phosphorylation of p38MAPK in CVB3 - induced murine DCM.