2-BFI对EAE大鼠中枢神经系统内小胶质细胞及MCP-1的影响

Effect of 2-BFI on microglia activation and MCP-1 expression in central nervous system of rats with experimental autoimmune encephalomyelitis

目的观察2-(2-苯并呋喃基)-2-咪唑啉[2-(-2-benzofuranyl)-2-imidazoline,2-BFI]对实验性自身免疫性脑脊髓炎(EAE)大鼠中枢神经系统内小胶质细胞及MCP-1的影响,并探讨其保护EAE大鼠的作用机制。方法 50只雌性SD大鼠随机分为EAE组、2-BFI低剂量组、2-BFI中剂量组、2-BFI高剂量组及对照组,每组10只,采用豚鼠脊髓匀浆免疫诱导SD大鼠建立EAE模型,观察每组大鼠发病情况并进行临床症状评分;采用HE染色和LFB髓鞘染色观察中枢神经系统的病理变化,对其炎症浸润程度加以评分;用免疫组化法测定脑干中激活的小胶质细胞及MCP-1阳性细胞数量。结果与EAE组比较,大、中、小剂量2-BFI干预组大鼠EAE发病率下降,临床症状减轻,潜伏期延长,中枢神经系统内炎性细胞浸润减少,2-BFI中剂量组在EAE临床症状和病理学改变方面差异有统计学意义(P<0.05);免疫组化结果显示,与EAE组比较,2-BFI中剂量组的活化的小胶质细胞数及MCP-1阳性细胞数均减少(P<0.05)。结论中剂量2-BFI对EAE大鼠具有神经保护作用,其作用机制可能与2-BFI抑制小胶质细胞的激活,减少MCP-1的表达有关。

Objective To investigate the effects of 2- （- 2- benzofuranyl）- 2- imidazoline （2- BFI） on microglia activation and MCP- 1 expression in central nervous system （CNS） of rat with experimental autoimmune encephalomyelitis （EAE）. Methods Fifty female Sprague- Dawley（SD） rats were randomly divided into five groups：control group（n=10）, EAE model group（n=10）, low dose （1.5mg/kg ） 2- BFI group （n=10）, intermediate dose （3 mg/kg） 2- BFI group （n=10） and high dose （6mg/kg） 2- BFI group （n=10）. The model of EAE was induced by injection of guinea pigs spinal cord homogenate （GPSCH）in SD rats. The severity of EAE was scored according to the signs and symptoms. The pathological changes were observed with Hematoxylin- eosin stain-ing and Luxol Fast blue dyeing, then the degree of inflammatory infiltration was evaluated. The changes of activated microglia and MCP- 1 positive cells in brainstem were counted by immunohistochemistry. Results Compared with EAE group, rats in inter-mediate dose 2- BFI treatment groups had lower incidence of disease, prolonged latency, decreased CNS inflammation and de-myelination （P＆lt;0.05）. Immunohistochemical results showed that the numbers of activated microglia and MCP- 1 positive cells were significantly reduced in intermediate dose 2- BFI group compared with the EAE group （P＆lt;0.05）. Conclusion 2- BFI at in-termediate dose （3mg/kg） has a beneficial neuroprotective effect on EAE, which may be related to inhibition of microglia activation and reduction of MCP- 1 expression.