中文摘要：

目的：研究大鼠坐骨神经预损伤后背根神经节中mi RNomes改变对脊髓后索损伤修复的影响。方法：39只雌性Wistar大鼠随机分为A、B、C、D组。A组（n=12）坐骨神经损伤造模后7d进行T10节段脊髓后索损伤造模,B组（n=12）仅进行T10节段脊髓后索损伤造模,C组（n=12）仅进行坐骨神经损伤造模,D组（n=3）不进行任何造模操作。A组和B组分别于脊髓后索损伤造模后4h、3d、7d、14d取背根神经节行总RNA提取和Western blot检测,于脊髓后索损伤造模后14d取损伤中心脊髓组织行神经丝蛋白200（NF-200）免疫组织化学染色和HE染色;C组于A组各时间点取材的同时取背根神经节行总RNA提取和Western blot检测;D组取背根神经节行总RNA提取和Western blot检测。对A、B两组各时间点背根神经节mi RNA表达谱进行微阵列芯片分析和生物信息学分析,观察与坐骨神经预损伤促进脊髓后索损伤修复有关的mi RNA,选出A组中与B组相比变化倍数明显、经过生物信息学分析靶蛋白为Dusp4的mi R-199a-5p进行研究。并用RT-q PCR技术对各组mi R-199a-5p及A、B和D组Dusp4 m RNA表达进行检测,用Western blot技术检测各组Dusp4蛋白以及A、D组p38蛋白和p-p38蛋白,对A组和B组脊髓后索损伤中心脊髓组织用NF-200免疫组织化学染色及HE染色观察损伤脊髓的恢复情况。结果：芯片分析结果显示mi R-199a-5p在A组各个时间点表达与D组相比明显下调,B组mi R-199a-5p在脊髓后索损伤后4h表达与D组相比上调,3d、7d和14d的表达量无明显变化。RT-q PCR结果显示A组各时间点mi R-199a-5p表达与D组相比下调（P〈0.05）,B组mi R-199a-5p在脊髓后索损伤后4h表达与D组相比上调（P〈0.05）,3d、7d和14d的表达量与D组比较无明显变化,C组各时间点mi R-199a-5p表达与D组比较无明显变化。A组和B组各时间点Dusp4 m RNA表达与D组相比无明显变化。A组Dusp4蛋白在脊髓后索损伤后各个时间点与D组

英文摘要：

Objectives： To study the effect of alteration of mi RNomes after sciatic nerve conditioning injury on the repairment of dorsal column lesion. Methods： Thirty-nine female Wistar rats were divided randomly into four groups, group A, B, C and D. Group A（n=12） underwent dorsal column lesion on the 10 th thoracic vertebra at the 7th day after sciatic nerve conditioning injury. Group B（n=12） underwent only dorsal column lesion. Group C（n =12） underwent only sciatic nerve injury. Group D（n =3） was used as blank control. The dorsal root ganglias of group A and B were excised for total RNA isolation and western blot at 4 hours, 3 days, 7 days and 14 days after dorsal column lesion. The spinal cord tissues of lesion sited in group A and B were harvested at 14 days after dorsal column lesion for immunohistochemistry of neurofilament-200（NF-200） and hematoxylin-eosin staining. The dorsal root ganglias of group C were harvested at same time points for total RNA isolation and Western blot. The dorsal root ganglias of group D were harvested for total RNA isolation and Western blot. To study its mechanism, the mi RNA profiles of dorsal root ganglias in group A and B were investigated by Microarray and bioinformatics. The significantly changed mi RNA mi R-199a-5p whose target was Dusp4 was screened out. RT-q PCR was used to detect the expression of mi R-199a-5p in each group and the expression of Dusp4 m RNA in group A, B and D. Western blot was applied to test the expression of Dusp 4 protein in each group and the expression of p38 protein and p-p38 protein in group A and D. Immunohistochemistry of NF-200 and hematoxylin-eosin staining were used to investigate the repairment of dorsal column lesion. Results： Microarry revealed that mi R-199a-5p downregulated at each time point of group A and upregulated at 4h of group B, however the expression of mi R-199a-5p in group B did not alter significantly at 3d, 7d, and 14 d after dorsal column lesion compared with that of group D. RTq PCR showed that mi R-199a