转铁蛋白靶向脂质体转导SDF-1治疗大鼠缺血性脑卒中

Stromal Cell Derived Factor-1 Transfered by Transferrin Targeted Liposomes for Treating Ischemic Stroke of Rats

目的通过转铁蛋白靶向脂质体将外源性SDF-1基因跨血脑屏障转运至脑缺血大鼠脑内,观察SDF-1在脑缺血大鼠脑内的表达及对神经功能恢复的作用。方法将脑缺血大鼠分为两组,分别注射Tf-SDF-1-PLs和生理盐水,观察SDF-1是否可以进入脑内实现高表达,并对新生血管、大鼠神经功能评分和脑血流量进行检测,评估Tf-SDF-1-PLs的治疗作用。结果药物注射24h后,Tf-SDF-1-PLs治疗组可见SDF-1 mRNA在脑内表达升高,而生理盐水注射组无SDF-1mRNA表达。药物注射48h后,检测脑中SDF-1蛋白的表达,免疫荧光检测脑中SDF-1染色,提示Tf-SDF-1-PLs治疗组的SDF-1蛋白表达均高于生理盐水注射组(P<0.05)。药物注射21天后,Tf-SDF-1-PLs治疗组的神经功能评分高于生理盐水注射组(P<0.05),新生血管数量高于生理盐水注射组(P<0.05),恢复的脑血流高于生理盐水注射组(P<0.05)。激光共聚焦结果提示SDF-1主要在胶质细胞中表达,Tf-SDF-1-PLs治疗组脑缺血大鼠的体重恢复早于生理盐水注射组。结论 Tf-SDF-1-PLs可以将SDF-1基因转运到脑缺血大鼠脑内,实现高表达。SDF-1可以发挥促进血管新生的作用,进而促进了脑血流量的恢复,有助于脑缺血大鼠神经功能的改善。

Objective Exogenous SDF - 1 gene was delivered by transferrin targeted liposomes crossing the blood brain barrier into ischemic brain. The expression of SDF - 1 in the ischemic brain was detected and the effect of promoting the recovery of neurological func- tion was observed. Methods Cerebral ischemic rats were randomly divided into two groups, and were respectively injected Tf- SDF - 1 - PLs and saline. Whether SDF - 1 could be delivered into brain and achieved high expression was observed. The effect of Tf - SDF - 1 - PLs was evaluated by vasculogenesis, neurological score and cerebral blood flew. Results After 24 hours of drug injection, SDF - 1 mRNA was increased in Tf - SDF - 1 - PLs group, but no SDF - 1 mRNA expression in saline group. After 48 hours of drug injection, the expression of SDF - 1 protein in Tf - SDF - 1 - PLs group was higher than that in saline group （P 〈 O. 05 ）. The quantity of SDF - 1 posi- tive cells in Tf- SDF - 1 - PLs group was higher than that in saline group （P 〈 0.05）. After 21 days of drug injection, the neurologic score in Tf - SDF - 1 - PLs group was much higher than that in saline group （P 〈 O. 05 ） , the quantity of neovascularization was more than that in saline group （P 〈 O. 05） , and the recovery of blood flew in Tf - SDF - 1 - PLs group was higher than that in saline group （P 〈 0.05）. The result of confocal laser scanning demonstrated SDF - 1 was mainly expressed in glial cells, and the rat weight in Tf - SDF - 1 - PLs group restored faster than that in saline group. Conclusion Exogenous SDF - 1 gene could be delivered into isehemie brain by transferrin targeted liposomes. The high expression of SDF - 1 gene in ischemic brain could promote angiogenesis, promote the recovery of cerebral blood flow and improve the neurologic function.