脑源性神经生长因子/microRNA-195在r创伤性脑损伤中的作用研究

摘要

目的 探讨脑源性神经生长因子(brain-derived neurotrophic factor,BDNF)/microRNA-195(miR-195)在创伤性脑损伤(traumatic brain injury,TBI)中的作用.方法 TBI患者入院及建立TBI大鼠模型后,分别采用ELISA和RT-PCR法检测TBI患者及大鼠模型中BDNF和miR-195的含量,并分析BDNF和miR-195之间的关系,进一步确定其对神经细胞N2A和SY5Y凋亡水平的影响;采用CCK-8实验检测BDNF和miR-195对N2A和SY5Y增殖能力的影响;应用NSS评分对BDNF/miR-195治疗TBI大鼠的疗效进行评价.结果 TBI患者入院时血清BDNF水平显著低于健康组(P<0.05);TBI大鼠脑组织中BDNF水平先升高后降低,且低于正常水平[对照组:0.5 h时,(177.0±20.4)μg;48 h时,(181.2±19.4)μg.重度组:0.5 h时,(300.5±31.2)μg;48 h时,(103.6±21.0)μg](P<0.05或P<0.01);而TBI患者和大鼠模型中miR-195水平均显著升高,并高于正常水平(P<0.01);BDNF可促进神经细胞生长增殖,抑制其凋亡,但miR-195同BDNF作用相反,其可抑制神经细胞生长增殖并促进其凋亡;BDNF可通过抑制miR-195的表达进而达到促进细胞生长增殖、抑制细胞凋亡,并起到改善神经功能的疗效.结论 BDNF/miR-195具有促进神经细胞生长,抑制凋亡,改善神经功能,可为临床上TBI的治疗提供新的靶点.%Objective To explore the effect of brain-derived neurotrophic factor (BDNF)/miR-195 on traumatic brain injury (TBI).Methods Following admission of the TBI patients and development of the TBI rat model , the levels of BDNF and miR-195 were detected by ELISA and RT-PCR.The relationship between BDNF and miR-195 was detected by Western blotting , and the effects of BDNF and miR-195 on the apoptosis of N2A and SY5Y and on the proliferation of N2A and SY5Y by CCK-8 were identified.And the efficacy of BDNF/miR-195 on TBI was evaluated by NSS score system .Results The serum BDNF level of the TBI patients at admission was significantly lower than that of the healthy group (P<0.05), and the BDNF level in the brain tissue of the TBI rats increased at first and then decreased, and it was obviously lower than the normal level (P<0.05 or P<0.01).The levels of miR-195 in the TBI patients and rats all significantly elevated and were higher than the normal level (P<0.01).BDNF could enhance nerve cell growth and inhibit apoptosis , while miR-195 acted antagonistically to inhibit the growth of nerve cells and promote apoptosis .The effects of BDNF were to promote cell growth and inhibit cell apoptosis by inhibiting the expression of miR -195 and improving the function of nerve cells . Conclusion BDNF/miR-195 could promote nerve cell growth , inhibit apoptosis and improve nerve function , which provided a new tar-get for the treatment of traumatic brain injury .