摘要
目的 采用脑出血(ICH)患者来源的诱导多能干细胞(iPSCs)进行移植治疗ICH大鼠模型,探讨其神经功能恢复的可能机制.方法 采用胶原酶注入法制作ICH大鼠模型.将制作成功的ICH大鼠模型随机分为3组,即假手术组(Sham组)、磷酸盐缓冲液(PBS)组及iPSCs组,观察iPSCs在大鼠脑内的存活,迁移及分化情况;通过改良神经功能评分(mNSS)及改良肢体放置试验(MLPT)评分来动态观察ICH大鼠的神经功能恢复情况;通过免疫组织化学染色及Western blot法监测血管内皮生长因子(VEGF)和层粘连蛋白(LN)的表达.结果 PSCs组的mNSS评分在14 d(2.60±0.70)和28 d(1.20±0.48)均较PBS组14 d(4.50±0.71)和28 d(3.00±0.52)明显改善(P<0.05).iPSCs组的MLPT评分在14 d(2.00±0.92)和28 d(1.20±0.85)均较PBS组14 d(2.60±0.91)和28 d(1.80±0.89)明显改善(P<0.05).iPSCs组血肿周围组织中的VEGF(140.76±1.58)与LN(140.22±0.67)的表达水平较PBS组明显增高(P<0.05).结论 iPSCs移植能促进ICH大鼠的神经功能的恢复,其机制可能是通过调节血肿周围组织中的VEGF和LN的表达水平来实现的.
Objective This study used a rat model of intracerebral hemorrhage (ICH) and induced pluripotent stem cells (iPSCs) derived from a patient with ICH to investigate the possible mechanism that underlies the effect of transplantation therapy on neurological function in the rat ICH model.Methods The rat ICH model was prepared using collagenase injection.The successfully established rats with ICH were randomly divided into three groups,including the sham group,the phosphate buffer (PBS) group,and the iPSC group.The survival,migration and differentiation of the iPSCs in the rat brain were observed.The recovery of neurological function in the ICH rats was monitored dynamically using modified neurological severity scores (mNSS) and the modified limb placement test (MLPT).The expression levels of vascular endothelial growth factor (VEGF) and laminin (LN) were detected via immunohistochemical staining and Western blotting.Results The mNSS scores of the rats in the iPSC group on day 14 (2.60 ± 0.70) and day 28 (1.20 ± 0.48) were significantly improved in comparison to the PBS group on day 14 (4.50 ± 0.71) and day 28 (3.00 ±0.52,P〈 0.05).The MLPTscores of the rats in the iPSC group on day 14 (2.00 ± 0.92) and day 28 (1.20 ± 0.85) were significantly improved in comparison to the PBS group on day 14 (2.60 ±0.91) and day 28 (1.80 ±0.89,P 〈 0.05).The expression levels of VEGF (140.76 ± 1.58) and LN (140.22 ±0.67) in the perihematomal tissue of the rats in the iPSC group were significantly higher than those of the PBS group (P 〈 0.05).Conclusion The transplantation of iPSCs could promote the recovery of neurological function in rats with ICH,potentially by regulating the expression levels of VEGF and LN in the perihematomal tissue.
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2016年第5期1250-1252,共3页
Chinese Journal of Experimental Surgery
关键词
诱导多能干细胞
脑出血
血管内皮生长因子
层粘连蛋白
Induced pluripotent stem cells
Intracerebral hemorrhage
Vascular endothelial growth factor
Laminin