不同途径移植bFGF修饰骨髓间充质干细胞治疗重型脑外伤的对比研究

Comparative study on bFGF-transfected BMSCs by different pathways for treating heavy traumatic brain injury

目的比较不同途径移植bFGF修饰骨髓间充质干细胞治疗重型脑外伤的疗效。方法 48只成年SD大鼠随机分为3个治疗组和1个对照组,脑外伤后经尾静脉组(A组)、脑室和尾静脉联合组(B组)、脑室注射组(C组)移植bFGF修饰BMSCs。采用行为测试试验评分观察肢体功能恢复,采用免疫组化法观察并比较第3、7、14天大鼠海马及损伤区域Brd U阳性细胞表达情况。结果 3个治疗组前肢放置试验和平衡试验评分均优于对照组,3个治疗组前肢放置试验脑室注射组优于联合治疗组和尾静脉注射组,差异均有统计学意义(P<0.05);3个治疗组平衡试验脑室注射组优于联合治疗组和尾静脉注射组,差异均有统计学意义(P<0.05);3个治疗组中大鼠海马第3、7、14天出现的Brd U阳性细胞数A组为(329.42±25.34)、(454.23±17.88)、(303.38±22.14),B组为(370.08±10.53)、(499.32±12.79)、(367.41±20.06),C组为(451.47±22.21)、(585.36±29.54)、(431.06±20.14)。损伤区域第3、7、14天出现的Brd U阳性细胞数A组为(269.17±5.34)、(401.08±12.02)、(233.45±35.42),B组为(279.00±10.53)、(408.08±8.05)、(246.12±31.21),C组为(391.46±19.87)、(475.75±20.64)、(370.21±26.32),均明显多于对照组,差异均有统计学意义(P<0.05);脑室注射组多于联合治疗组、尾静脉注射组,差异均有统计学意义(P<0.05)。结论三种移植方式均可促进肢体功能的恢复,但经脑室移植治疗效果最为明显。

Objective To compare the effect of bFGF-transfected bone mesenchymal stem cells（BMSCs） by different pathways for treating heavy traumatic brain injury（TBI）. Methods Forty-eight adult SD rats were divided into 3 treatment groups and the control group（group D） at random. The injection of bFGF-transfected BMSCs was given to rats after TBI via the tail vein（tail vein treatment group, group A）, tail vein and ventricle（combination treatment group, group B）, ventricle（ventricle treatment group, group C）. The restoration of limbs function was observed by behavior test grading. The expression of Brd U-labeled cells were counted and compared in the hippocampus and damage region by immunohistochemical method 3 d, 7 d, 14 d after TBI. Results Both of the grading of forelimb placing test and beam balance test examines in the 3 treatment groups（group A, B, C） were better than those in the control group.The grading of forelimb placing test in group C were significantly better than that in group A or group B（P〈0.05）. The grading of beam balance test in group C were significantly better than in group A or group B（P〈0.05）. Brd U-labelde cells in the hippocampus 3 d, 7 d, 14 d after TBI were respectively（329.42±25.34）,（454.23±17.88）,（303.38±22.14） in group A,（370.08 ± 10.53）,（499.32 ± 12.79）,（367.41 ± 20.06） in group B, and（451.47 ± 22.21）,（585.36 ± 29.54）,（431.06 ± 20.14） in group C. Brd U-labelde cells in the damage region 3 d, 7 d, 14 d after TBI were respectively（269.17±5.34）,（401.08±12.02）,（233.45±35.42） in group A,（279.00±10.53）,（408.08±8.05）,（246.12±31.21） in group B,（391.46±19.87）,（475.75±20.64）,（370.21±26.32） in group C. Compared with the control group, Brd U-labelde cells in group A, B and C increased significantly（P〈0.05）, and that in group C were significantly better than group A or group B（P〈0.05）. Conclusion Restoration of limbs function after TBI can be promoted by the three pathways（tail vein, tail vein and ventricle, ventricle）. However, this effect can be improved most significantly by the ventricle pathway.