角质生长因子、缺氧诱导因子修饰的骨髓间充质干细胞对大鼠脊髓损伤修复的影响

Effects of KGF,HIF-1 and Their Interplay in Repair of Spinal Cord Injuries in Rats

目的探讨角质生长因子(KGF)与缺氧诱导因子(HIF)修饰的骨髓间充质干细胞(MSCs)对大鼠脊髓损伤(SCI)的修复作用。方法全骨髓贴壁法分离培养骨髓MSCs;携带重组KGF和HIF-1基因的腺病毒感染修饰MSCs,自由落体法制备大鼠SCI模型,分为MSCs组、KGF-MSCs组、HIF-1-MSCs组及KGF/HIF-MSCs组,分别于损伤部位移植无修饰、KGF因子修饰、HIF-1因子修饰及KGF/HIF双修饰的骨髓MSCs,应用联合行为学评分评价大鼠运动能力恢复情况,观察脊髓组织病理学变化及神经细胞修复情况,并测定SRY及腺病毒基因Adeno的表达水平。结果KGF-MSCs、HIF-1-MSCs及HIF-MSCs组联合行为学评分均高于MSCs组,且KGF/HIF-MSCs组效果最明显(P<0.05)。4组大鼠脊髓组织中细胞数目增加,神经细胞坏死减少,均高表达SRY及Adeno基因。结论细胞因子KGF、HIF可增强骨髓MSCs移植后SCI修复作用。

Objective To investigate the repair effect of kinetics gain factor（ KGF） and hypoxia-inducible factor（ HIF） mediated bone marrow mesenchymal stem cells（ MSCs） for spinal cord injuries（ SCI） in rats. Methods Bone marrow MSCs were isolated and cultured using whole bone marrow cells adherence method,and were modulated with adenovirus infections restructured by KGF and HIF-1. The SCI models were established using free falling body hitting method,and then were divided into four groups. The injury parts of MSCs,KGF-MSCs,HIF-1-MSCs and KGF / HIF-MSCs groups were transplanted with MSCs,KGF-MSCs,HIF-1-MSCs and KGF / HIF-MSCs respectively. The recovery conditions of locomotory capabilities were evaluated using combined praxiology score,and the medullary histopathological changes and repair of nerve cells were observed,and expression levels of Sry and adenovirus genes were detected. Results The combined praxiology scores in KGF-MSCs,HIF-1-MSCs and KGF / HIF-MSCs groups were significantly higher than that in MSCs group,and the effect in KGF / HIF-MSCs was the most obvious one（ P 0. 05）. In the four groups,the cell numbers in myeloid tissues were increased,and numbers of nerve necrocytosis were decreased,and SRY and adenovirus genes were highly expressed. Conclusion KGF and HIF-1 can enhance SCI repair effect after transplantation of bone marrow MSCs.