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目的探讨轴突生长抑制因子Lingo-1在大鼠脑白质损伤(WMD)发生中的机制及脑源性神经营养因子(BDNF)对WMD脑组织的可能保护作用。方法参照Back方法制作2日龄新生大鼠WMD模型,WMD鼠脑室内注射BDNF为干预手段,应用原位杂交和荧光定量RT-PCR检测对照组(假手术组)、WMD组、BDNF处理组缺氧缺血后8、24、48、72 h及7 d脑组织Lingo-1 mR-NA的表达。结果对照组脑组织Lingo-1 mRNA的表达较少,Lingo-1 mRNA在WMD组大脑各部分广泛分布,尤其皮质和海马分布更为密集。WMD组在缺氧缺血后8、24 h和48 h脑组织Lingo-1mRNA的表达均明显高于对照组(P<0.05),在缺氧缺血后48 h达高峰后开始下降,但72 h及7 d脑组织Lingo-1 mRNA的表达仍高于对照组(P<0.05);BDNF处理组脑组织Lingo-1 mRNA表达在处理后8、24 h较WMD组升高(P<0.05),后逐渐下降,48、72h Lingo-1 mRNA水平均低于同时间点WMD组(P<0.05);7 d时两组Lingo-1 mRNA水平比较,差异无统计学意义(P>0.05)。BDNF处理组各时间点Lingo-1 mRNA表达均高于对照组(P<0.05)。结论WMD新生大鼠脑组织Lin-go-1 mRNA较对照组在大脑各部分分布增多,表达增强,推测Lingo-1可能参与了WMD中的神经损伤和轴突再生抑制的机制。BDNF可在一定程度上降低WMD后Lingo-1 mRNA的表达水平,可能对WMD大鼠脑具有一定的保护作用。
Objective To investigate the mechanism of axon growth inhibitory factor Lingo-1 in the development of white matter damage (WMD) in rats and the possible protective effect of brain derived neurotrophic factor (BDNF) on brain WMD. Methods The 2-day-old neonatal WMD model was made by the Back method. The BDNF was injected into the brain of WMD rats as an intervention. The in situ hybridization and real-time fluorescence quantitative RT-PCR were used to detect the control group (sham operation group), WMD group and BDNF treatment group Expression of Lingo-1 mR-NA at 8, 24, 48, 72 h and 7 d after oxygen ischemia. Results There was less expression of Lingo-1 mRNA in brain tissue of control group. Lingo-1 mRNA was widely distributed in brain of WMD group, especially in cortex and hippocampus. The expression of Lingo-1mRNA in brain tissue of WMD group was significantly higher than that of control group at 8, 24 and 48 h after hypoxia-ischemia (P <0.05), but decreased at 48 h after hypoxia-ischemia The expression of Lingo-1 mRNA in brain tissue of rats in BDNF group was higher than that in WMD group at 8 and 24 h after treatment (P <0.05) (P <0.05). The levels of Lingo-1 mRNA in 48 and 72h groups were lower than that in WMD group at the same time points (P <0.05). There was no significant difference in Lingo-1 mRNA levels between the two groups on the 7th day (P> 0.05). The expression of Lingo-1 mRNA in BDNF-treated group at each time point was higher than that in control group (P <0.05). Conclusion The expression of Lin-go-1 mRNA in brain tissue of WMD newborn rats increased more than that of the control group, suggesting that Lingo-1 may be involved in the mechanism of nerve injury and axon regeneration inhibition in WMD. BDNF can reduce the expression of Lingo-1 mRNA to a certain extent after WMD, which may have a protective effect on WMD rat brain.