小鼠脊髓脱髓鞘病变后LINGO-1的动态表达变化

Dynamic expression of LINGO-1 after spinal cord demyelination in mice

目的观察LINGO-1在溶血卵磷脂注射诱导脊髓脱髓鞘病变小鼠脊髓中的动态表达变化。方法模型组小鼠接受1%溶血卵磷脂注射至T8-9和T9-10胸椎节段的脊髓双侧腹外侧区,诱导脱髓鞘病变。甲苯胺蓝染色观察病变范围;实时定量RT-PCR和western blot检测病变区脊髓LINGO-1的表达变化。结果溶血卵磷脂注射1d后,病变区脊髓LINGO-1mRNA和蛋白表达上调均最为显著,其后逐渐下降,LINGO-1mRNA在2周后接近空白对照,而LINGO-1蛋白至4周时仍略高于空白对照。结论LINGO-1在脊髓脱髓鞘病变早期即上调并呈一定规律性改变,提示其与脊髓脱髓鞘病变有关;对于治疗脊髓脱髓鞘病变,LINGO-1拮抗剂应在损伤早期使用。

Objective To investigate the dynamic expression of LINGO-1 after spinal cord demyelination induced by lysolecithin injection in mice. Methods 39 female C57B1/6 mice were used in this study and were randomly divided into 4 groups： normal controls （group A： 6 mice）, sham operated controls （group B： 6 mice）, operated groups （group C： 24 mice）, and model detected group （group D： 3 mice）. Animals in group C and D were treated with lysolecithin injection. Then the mice in group C were divided into lday, lweek, 2 weeks, and 4 weeks sub-groups （6 mice for each group）, and the animals in group D were used to determine the demyelinated area. Demyelination were induced by 1% lysolecithin in PBS injection into VLF region between T8-9 and T9-10 segments in mice spinal cord. Demyelinated area were detected by toluidine blue staining. Dynamic expression of LINGO-1 mRNA and protein were analyzed by using quantitative real-time RT-PCR （QRT-PCR） and Western Blot. Results QRT-PCR and western Blot showed an increased expression of LINGO -1 mRNA and protein post-lysolecithin injection, and the peak time was 1 day post operation. LINGO -1 mRNA decreased to the normal level after 2 weeks post-injection, and LINGO-1 protein decreased slowly and was still slightly higher than normal at 4 weeks post-injection. Conclusion These results show the higher expression of LINGO-1 after spinal crod demyelination and suggest which may involved in the early stages of spinal cord demyelinating pathophysiology. Antagon of LINGO-1 treatment should be applied at the early stage for spinal cord demyelinating disease.