左旋精氨酸对大鼠下肢缺血后血管新生的影响及其机制的研究  

The effect and mechanism of L-Arginine on angiogenesis in rats with ischemic hindlimb

作　　者：李皓雲[1] 黄震浩[1] 黄婧娟[1] 段俊丽[1] 柳洁[2] 

机构地区：[1]上海交通大学医学院附属新华医院,200092 [2]山西省人民医院

出　　处：《山西医药杂志（上半月）》2013年第5期492-494,I0001,共4页Shanxi Medical Journal

基　　金：上海市科学技术委员会自然科学基金(11NM0503600)

摘　　要：目的探讨左旋精氨酸对大鼠下肢缺血后血管新生的影响及其相关机制。方法将SD雄性大鼠随机分为两组:左旋精氨酸组(LA组)和生理盐水对照组(CL组),每组6只。戊巴比妥钠麻醉后仰卧位固定,钝性分离皮肤肌肉等外周组织后,分别手术结扎动物左下肢股动、静脉及其分支后缝合,建立下肢缺血模型。两组动物分别给予左旋精氨酸以及生理盐水,每只动物每日均灌胃给药一次。术后第14天取大鼠缺血下肢的内收肌缺血组织。用免疫组织化学法检测CD31在缺血肌肉组织中的表达及新生血管数量,用蛋白印迹法检测缺氧诱导因子(HIF)-1蛋白表达量,用酶联免疫吸附试验测定血管内皮生长因子(VEGF)含量。结果左旋精氨酸组缺血肌肉组织中毛细血管计数明显高于对照组[(169±15)个/mm2与(111±8)个/mm2,P<0.05],HIF-1蛋白表达明显高于对照组[(0.73±0.06)与(0.22±0.08),P<0.05],VEGF含量也明显高于对照组[(408±28)μg/L与(327±27)μg/L,P<0.05]。结论左旋精氨酸对缺血后血管新生有促进作用,这一作用可能与左旋精氨酸诱导HIF-1表达上调,增加对缺氧耐受,促进VEGF通过多条信号通路诱导新生血管产生保护内皮功能。Objective To investigate the effect and the possible mechanism of L-Arginine on angiogenesis in rats with ischemic hindlimb. Methods Male SD rats were randomized divided into 2 groups, L-Arginine group and control group, 6 rats for each group. Lower limb ischemia model was established, each group was intragastri- cally administratered one time every day. 14 days after surgery, ischemic tissues of adductor were collected for several tests, including immunohistochemical staining for CD31, HIF-1 and VEGF protein expression by Western blot and vascular endothelial growth factor （VEGF） level by enzyme-linked immunosorbent assay. Results The capillary count showed that the angiogenesis situation of LA group was significantly greater than that of control group [（169±15）/mm2 vs（111±8）/mm2 ,P〈0.05]. The HIF-1 protein expression in LA group was remarkably higher than that in control group [（0.73±0.06） vs （0.22±0. 08）, P〈0. 051. Comparing with control group, VEGF level in PC group increased notably [（408±28）μg/L vs （327±27）μg/L,P〈0. 05]. Conclusion L-Ar- ginine plays a positive role in angiogenesis after ischemia. L-Arginine may induce upregulation of HIF-1 and de- creas HIF-1 response to hypoxia and reduce hypoxic damage by increasing VEGF and promoting the neovascularization through multiple signaling pathways consequently.

关 键 词：新生血管化 病理性 一氧化氮 精氨酸 缺氧诱导因子1 血管内皮生长因子类 

分 类 号：R965[医药卫生—药理学]