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目的:探讨移植人脐带间充质干细胞(h UC-MSCs)对脑白质损伤新生大鼠脑内胶质细胞源性神经营养因子(GDNF)含量的影响。方法:取3日龄清洁级Sprague-Dawley大鼠,随机分为实验组、对照组和假手术组,实验组和对照组均结扎左侧颈总动脉并吸入6%的氮氧混合气体4 h,假手术组仅游离血管,不予结扎及缺氧处理,实验组术后24 h内腹腔内注射0.5 ml h UC-MSCs(细胞浓度为2×10~6ml~(-1)),连续注射3 d。对照组及假手术组注射相同剂量生理盐水。HE染色观察大体病理变化,采用免疫组织化学方法检测各组大鼠5、7和14日龄时(各组各时间点6只大鼠)脑内GDNF蛋白表达情况。结果:HE染色显示,7日龄时实验组大鼠脑组织未见明显细胞水肿、变性和坏死;对照组大鼠可见部分神经细胞变性、坏死;假手术组大鼠脑组织细胞轮廓正常,排列整齐。5、7、14日龄时假手术组正常脑内均含有少量的GDNF,而对照组大鼠脑内GDNF蛋白表达量在各时间点均较假手术组增高(P<0.01),且呈逐渐下降趋势。实验组大鼠脑内GDNF蛋白表达量最高,5日龄时GDNF蛋白含量即增高明显,且呈逐渐升高趋势,14日龄时增高最明显。实验组3个时间点蛋白表达水平较对照组和假手术组均明显增高(P<0.01)。结论:h UC-MSCs能够促进脑白质损伤新生大鼠脑内GDNF分泌、神经功能恢复以及未成熟脑的发育。
Objective: To investigate the effects of transplanted human umbilical cord mesenchymal stem cells (h UC-MSCs) on glial cell line-derived neurotrophic factor (GDNF) in brain of white matter-damaged neonatal rats. Methods: Three-day-old clean Sprague-Dawley rats were randomly divided into experimental group, control group and sham operation group. The experimental group and control group were ligated with left common carotid artery and inhaled 6% The rats in the sham-operation group were only free of blood vessel. The rats in the experimental group were injected intraperitoneally with 0.5 ml h UC-MSCs (the cell concentration was 2 × 10 ~ 6 ml -1) 3 d. The control group and sham operation group were injected with the same dose of saline. The gross pathological changes were observed by HE staining. The expression of GDNF protein in brains of rats in each group was detected by immunohistochemistry at 5, 7 and 14 days of age (6 rats at each time point). Results: HE staining showed that at 7 days of age, no significant cell edema, degeneration and necrosis were found in the brain tissue of rats in experimental group. Some neurons in the control group showed degeneration and necrosis. neat. At 5, 7 and 14 days of age, the GDNF in the normal brain of the sham operation group was small, while the GDNF expression in the control group was higher than that of the sham operation group at each time point (P <0.01) Downtrend. GDNF protein expression was highest in the experimental group, GDNF protein content increased significantly at 5-day-old, and gradually increased, the highest increase at 14 days of age. The expression of protein in experimental group at 3 time points was significantly higher than that in control group and sham operation group (P <0.01). CONCLUSION: h UC-MSCs can promote GDNF secretion, neurological function recovery and immature brain development in brain of neonatal rats with white matter damage.