苦参素对实验性自身免疫性脑脊髓炎大鼠CCL2,CCR2mRNA表达的影响

目的:观察目前国际上公认的人类多发性硬化(MS)的理想动物模型-实验性自身免疫性脑脊髓炎(EAE)大鼠模型脊髓中单核细胞趋化蛋白2(CCL2),单核细胞趋化蛋白受体2(CCR2)mRNA表达,探讨苦参素对EAE大鼠的保护作用,为临床应用提供依据。方法:将50只雌性Wistar大鼠随机分5组,分别为正常组,模型组,苦参素低、高剂量组(150,250 mg·kg~(-1)),地塞米松组(1 mg·kg~(-1)),每组10只,自免疫当天起连续给药16 d,同期正常组、模型组ip等量生理盐水,观察记录大鼠的临床症状,并检查组织病理学变化,采用RT-PCR法检测脊髓中CCL2,CCR2 mRNA的表达。结果:与模型组比较,苦参素有效延迟EAE大鼠的发病时间,明显降低临床神经功能学评分(P0.01),改善EAE大鼠中枢神经系统炎症浸润(P0.01)和髓鞘脱失(P0.01)程度,下调脊髓中CCL2,CCR2 mRNA的表达(P0.01,P0.01)。结论:苦参素对EAE大鼠有防治作用,其作用机制可能与下调大鼠脊髓中CCL2,CCR2 mRNA的表达有关。

Effect of Matrine on Expression of CCL2,CCR2 mRNA in Experimental Autoimmune Encephalomyetic Rats

Objective: To observe the effect of matrine (MAT) on the expression of chemokine ligand-2 (CCL2) and its receptor CCR2 mRNA in experimental autoimmune encephalomyetic (EAE) rats in the internationally accepted models of multipe sclerosis (MS), investigate the possible mechanism of MAT preventive treatment for EAE rats and provide clinical evidence. Method: The 50 Wistar female rats were divided into five groups randomly (n=10 each group):normal group, model group, MAT low-dose group (150 mg · kg^-1), MAT high-dose group (250 mg · kg^-1), and dexamethasone group (1 mg · kg^-1). The MAT and dexamethasone were respectively injected intraperitoneally (ip) daily from day 0 post-immunization till to 17. At the same time, The model and normal group received the same amount of normal saline. The clinical symptoms were observed and recorded and the histopathological changes were detected. The expression levels of CCL2,CCR2 mRNA were detected using RT-PCR techniques. Result: Compared with model group, MAT obviously delayed the disease onset and ameliorated clinical symptoms of EAE (P<0.01), improved inflammatory infiltration (P<0.01) and demyelination (P<0.01) in central nervous system of EAE rats, and reduced the expression levels of CCL2/CCR2 mRNA in spinal cord (P<0.01, P<0.01). Conclusion: Matrine could prevent and treat EAE rats and the mechanism may be associated with reducing the expression of CCL2/CCR2 mRNA in spinal cord of EAE rats.