丹红注射液对大鼠局灶性脑缺血再灌注损伤血管内皮生长因子表达的影响

Effect of danhong injection on vascular endothelial growth factor in rats with focal cerebral ischemia reperfusion injury

目的研究丹红注射液对大鼠局灶性脑缺血再灌注损伤血管内皮生长因子(VEGF)表达的影响。方法 90只大鼠中,选择12只为假手术组,另78只经右侧翼腭动脉线栓willis环阻塞60 min后再灌注60 min,反复3次,建立大鼠局灶性脑缺血再灌注损伤的动物模型。术后7 d选择其中36只造模成功大鼠,随机分为模型组、丹红A组、丹红B组。四组大鼠均采用尾静脉注射给药治疗,并于治疗前及治疗14 d后分别检测各组动物血管内皮细胞生长因子(VEGF)蛋白质及VEGF mRNA、缺氧诱导因子-1a(HIF-1a)、HIF-1a mRNA、受体胎肝激酶1(FLK-1)、FLK-1 mRNA,脑组织TTC染色并测定脑梗死范围。结果治疗14 d后,丹红组VEGF蛋白质及VEGF mRNA、HIF-1a、HIF-1a mRNA、FLK-1、FLK-1 mRNA明显增高;TTC组织学检查显示,部分脑组织神经细胞溶合且排列紊乱,但脑梗死范围明显缩小。与模型组比较,各指标差异均有统计学意义(P<0.05);丹红A组、B组各指标比较差异无统计学意义(P>0.05)。结论丹红注射液可减轻大鼠局灶性脑缺血再灌注后血管内皮炎症反应程度,其作用机制可能与其促进VEGF分泌、拮抗Ca2+内流、松弛脑血管平滑肌、增加血管通透性、促进血管内皮细胞增殖、诱导缺血部位血管新生有关。

Objective To study the effects of danhong injection on vascular endothelial growth factor （VEGF） expression in rats with focal cerebral ischemia reperfusion injury. Methods Twelve rats were selected as sham operated group （control group ） , 78 rats received right pterygopalatine artery willis ring obstruction for 60 min and reperfusion for 60 min, the operation repeated for 3 times to establish the model of rats with focal cerebral ischemia reperfusion injury. Thirty-six successful model rats at 7 d after IR were randomly divided into model group, danhong A group and danhong B group. Rats in the 4 groups were medicated via tail vein injection. The protein content and mRNA expression of VEGF, hypoxia inducible factor-1 a （ HIF-1 a） and receptor in fetal liver kinase 1 （ FLK-1 ） were measured before treatment and at 14 d after treatment. The size of cerebral infarction was determined by brain tissue TFC stai- ning. Results Compared with model group, the protein content and mRNA expression of VEGF, HIF-1 a and FLK-1 in danhong groups were significantly higher at 14 d after treatment （P 〈 0. 05 ）, the size of cerebral infarction reduced significantly （ P 〈 0. 05 ）. There was no significant difference in the above indexes between the two danhong groups （ P 〉 0. 05 ）. Conclusion Danhong injection can reduce the vascular endothelial cell inflammatory reaction in rats with focal cerebral ischemia reperfusion injury. The mechanism may be related to the promotion of VEGF secretary, antagonism of Ca^2＋ inner flow, relaxation of vascular smooth muscle and increasing vascular permeability etc.