载脂蛋白E拟肽对创伤性脑损伤后脑组织血管再生的影响

Effect of apolipoprotein E peptide on angiogenesis after traumatic brain injury

目的 探讨载脂蛋白E（apoE）拟肽对创伤性脑损伤（TBI）后脑组织血管内皮生长因子（VEGF）、微血管密度（MVD）、血脑屏障（BBB）通透性和脑水肿的影响.方法 将256只C57BL/6J雄性基因野生型小鼠按随机数字表法分为正常对照组、假手术组、等渗盐水组、apoE拟肽干预组,每组又分为创伤后1d和3d两个亚组,每亚组32只.采用控制性气压冲击法构建小鼠TBI模型.apoE拟肽干预组为创伤后每24 h予以尾静脉注射apoE拟肽COG1410,其他组为创伤后每24 h予以尾静脉注射等渗盐水;创伤后1,3d,采用ELISA法、免疫组化、伊文思蓝和干湿重法分别检测脑组织VEGF表达情况、MVD、BBB通透性和脑组织含水量.结果 创伤后第1天,假手术组与正常对照组脑组织VEGF表达量、MVD计数、BBB通透性和脑组织含水量比较差异无统计学意义（P＞0.05）;apoE拟肽干预组与等渗盐水组脑组织VEGF表达量[（18.12±1.51） pg/ml∶（23.66±1.78） pg/ml]、MVD计数[（14.78±1.98）个/HP∶（19.25±2.23）个/HP]、BBB通透性[（0.45 ±0.02）∶（0.53 ±0.05）]和脑组织含水量[（79.05±0.17）％∶（79.77±0.22）％]比较均明显降低（P＜0.05）.创伤后第3天,假手术组与正常对照组脑组织VEGF表达量、MVD计数、BBB通透性和脑组织含水量比较差异无统计学意义（P＞0.05）;apoE拟肽干预组与等渗盐水组脑组织VEGF表达量[（28.77±2.01） pg/ml∶（34.52±1.93） pg/ml]、MVD计数[（20.67 ±2.58）个/HP∶（31.66±3.67）个/HP]、BBB通透性[（0.60 ±0.07）∶（0.79±0.10）]和脑组织含水量[（78.97±0.29）％∶（80.06±0.28）％]比较均明显降低（P＜0.05）.结论 apoE拟肽能有效降低TBI后脑组织血管的过度再生以及由血管过度再生引起的血管源性脑水肿.

Objective To study the effect of apolipoprotein E （apoE） peptide on the vascular endothelial growth factor （VEGF）,microvessel density （MVD）,permeability of blood-brain barrier （BBB） and brain edema following traumatic brain injury （TBI）.Methods A total of 256 C57BL/6J male wild-type mice were divided into control group,sham group,saline group,and apoE peptide group according to the random number table,with 64 mice per group.The mice models of TBI were constructed by the controlled cortex impact devices.The animals in apoE peptide group were injected in the tail vein with apoE peptide-COG1410 every 24 hours after injury,but in other groups saline injection therapy was used.Half of the animals （n =23 per group） were sacrificed at 1 and 3 days after injury.ELISA,immunohistochemistry,Evans blue and dry-wet method were respectively used to evaluate VEGF level,MVD,permeability of BBB and brain edema.Results One day after injury,the measures did not differ significantly between sham group and control group （P 〉 0.05）,but VEGF level [（18.12 ±1.51）pg/ml vs （23.66 ± 1.78）pg/ml],MVD [（14.78 ±l.98）/HP vs （19.25 ±2.23）/HP],permeabilityof BBB [（0.45 ±0.02） vs （0.53 ±0.05）] and brain water content[（79.05 ±0.17）% vs （79.77 ± 0.22） %] were lowered in apoE peptide group compared to saline group （P 〈 0.05）.Three days after injury,the measures revealed no significant differences between sham group and control group （P 〉 0.05）,but VEGF level [（28.77 ± 2.01） pg/ml vs （34.52 ± 1.93） pg/ml],MVD [（20.67 ± 2.58）/HP vs （31.66 ±3.67）/HP],permeability of BBB [（0.60 ±0.07） vs （0.79 ± 0.10）] and brain water content [（78.97 ± 0.29） % vs （80.06 ± 0.28） %] were lowered in apoE peptide group compared to saline group （P 〈 0.05）.Conclusion apoE peptide is effective in reducing the excessive angiogenesis and vasogenic brain edema caused by excessive angiogenesis after TBI.