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目的:观察组蛋白去乙酰化酶1(HDAC1)基因沉默的人脐带间充质干细胞(hUC-MSCs)静脉移植对创伤性脑损伤小鼠神经功能恢复的影响。方法:80只健康成年C57BL/6小鼠,利用立体定位仪和颅脑打击器制作中度脑损伤模型,分为Sham组、Vehicle组、hUC-MSCs移植组和联合组(n=20)。移植后第1、3、7、14、21和28天,采用改良神经功能损伤评分系统评价小鼠神经功能恢复情况;通过Morris水迷宫实验、挂线实验、新物体识别实验评价小鼠长期运动及认知功能。结晶紫染色评估小鼠的脑损伤体积和观察海马CA3区神经元形态学改变;湿重法检测脑含水量;伊文斯蓝染色检测血脑屏障的开放程度。结果:与Vehicle组相比,hUC-MSCs移植组和联合组小鼠神经功能损伤评分降低,水迷宫实验中逃避潜伏期增加、穿越平台次数及在平台象限停留时间增加,挂线时间和辨别指数增加,其中联合组各指标均有明显改善(P<0.05)。与hUC-MSCs移植组相比,联合组小鼠脑损伤体积减少、脑含水量降低、血脑屏障开放程度减轻(P<0.05),且海马CA3区神经元丢失减少。结论:HDAC1基因沉默的hU-MSCs移植对创伤性脑损伤小鼠有较好的神经保护作用。
OBJECTIVE: To observe the effects of hUC-MSCs with histone deacetylase 1 (HDAC1) gene silencing on the recovery of neural function after traumatic brain injury in mice. Methods: Eighty healthy adult C57BL / 6 mice were divided into Sham group, Vehicle group, hUC-MSCs transplantation group and the combination group (n = 20) by stereotactic apparatus and cranial brain striker. On the 1st, 3rd, 7th, 14th, 21st and 28th days after transplantation, the neurological functional recovery was evaluated by the improved neurological impairment score system. Morris water maze test, hanging line experiment and new object recognition test were used to evaluate the long-term And cognitive function. Crystal violet staining was used to assess brain injury volume in mice and morphological changes of hippocampal CA3 neurons were observed; wet weight was used to measure brain water content; Evans blue staining was used to detect the openness of blood-brain barrier. Results: Compared with Vehicle group, the scores of neurological impairment in hUC-MSCs transplantation group and combination group mice decreased, the escape latency increased, the number of crossing platform and the dwell time in the platform quadrant increased, and the time of line connection and discrimination index increased , In which the indexes in the combined group were significantly improved (P <0.05). Compared with the hUC-MSCs transplantation group, the brain injury volume, brain water content and the opening of the blood-brain barrier in the combination group were decreased (P <0.05), and the loss of neurons in the hippocampal CA3 region was reduced. Conclusion: HDAC1 gene silencing hU-MSCs transplantation has a good neuroprotective effect on traumatic brain injury in mice.