扩心方对阿霉素诱导扩张型心肌病大鼠心脏血管新生作用的影响

Effect of KXF on cardiac angiogenesis induced by Doxorubicin in rats with dilated cardiomyopathy

目的观察扩心方对阿霉素诱导扩张型心肌病大鼠心脏血管新生作用的影响。方法应用腹腔注射阿霉素诱导扩张型心肌病大鼠模型,60只SD大鼠随机分为空白组、模型组、扩心方低[1.8 mg/(kg·d)]、中[3.6 mg/(kg·d)]、高剂量组[7.2 mg/(kg·d)]及卡托普利组[5 mg/(kg·d)]。各组分别给予药物或生理盐水灌胃4周。造模结束后采用超声心动图检测大鼠心脏功能;HE、Masson染色观察大鼠心肌组织病理学改变;免疫组化观察大鼠心肌组织VEGF、α-SMA、CD31、CD34表达情况;Western blot观察大鼠心肌组织VEGFR-2蛋白表达水平。结果与正常组相比,模型组大鼠LVIDD及LVIDS值升高,EF及FS值降低(P<0.05),与模型组大鼠相比,扩心方高、中、低及卡托普利组大鼠LVIDD、LVIDS值降低,EF、FS值升高(P<0.05);与模型组相比,扩心方低、中、高剂量组及卡托普利组VEGF、CD31、CD34表达明显增加,且CD34表达呈剂量依赖性;扩心方高剂量组α-SMA较模型组表达增加明显;扩心方低、中、高剂量组及卡托普利组VEGFR-2蛋白表达较模型组均升高,其中扩心方低、中剂量组及卡托普利组升高显著(P<0.01)。结论扩心方可通过上调促血管新生因子VEGFR-2表达,增加阿霉素诱导扩张型心肌病大鼠心肌微血管密度,促进血管生成。

Objective To observe the effect of KXF on cardiac angiogenesis induced by doxorubicin in rats with dilated cardiomyopathy.Methods 60 SD rats were randomly divided into control group,model group,KXF-L group[1.8 mg/(kg·D)],KXF-M group[3.6 mg/(kg·D)],KXF-H group[7.2 mg/(kg·D)]and Captopril group[5 mg/(kg·D)].Each group was given drugs or normal saline by gavage for 4 weeks.After modeling,echocardiography was used to detect the cardiac function of rats;HE and Masson staining were used to observe the histopathological changes of rat myocardium;The expression of VEGF,α-SMA,CD31 and CD34 in rat myocardium was observed by immunohistochemistry;The expression of VEGFR-2 protein was observed by Western blot.Results Compared with the control group,the values of LVIDD and LVIDS in the model group increased and the values of EF and FS decreased(P<0.05).Compared with the model group,the values of LVIDD and LVIDS in the KXF-H group,KXF-M group,KXF-L group and captopril group decreased and the values of EF and FS increased(P<0.05);Compared with the model group,the expression of VEGF、CD31 and CD34 in KXF-L group,KXF-M group,KXF-H group and Captopril group increased significantly,and the expression of CD34 was dose-dependent;the expression ofα-SMA in KXF-H group increased significantly compared with the model group;The expression of VEGFR-2 protein in KXF-L group,KXF-M group,KXF-H group and Captopril group was significantly higher than that in model group(P<0.01).Conclusion KXF can increase myocardial microvessel density and promote angiogenesis in rats with doxorubicin induced dilated cardiomyopathy by up regulating the expression of VEGFR-2.