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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(P<0.01),改善EAE大鼠中枢神经系统炎症浸润(P<0.01)和髓鞘脱失(P<0.01)程度,下调脊髓中CCL2,CCR2 mRNA的表达(P<0.01,P<0.01)。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。
OBJECTIVE: To observe the current internationally recognized ideal animal model of human multiple sclerosis (MS) - Experimental Autoimmune Encephalomyelitis (EAE) rat model of monocyte chemoattractant protein 2 (CCL2), monocytes Chemokine receptor 2 (CCR2) mRNA expression, to explore the protective effect of oxymatrine on EAE rats, provide the basis for clinical application. Methods: Fifty female Wistar rats were randomly divided into five groups: normal group, model group, low and high dose oxymatrine group (150, 250 mg · kg -1) and dexamethasone group (1 mg · kg -1) kg), 10 rats in each group were dosed continuously for 16 days from the day of immunization. The rats in the normal group and the model group were given the same amount of saline at the same time. The clinical symptoms of the rats were observed and the histopathological changes were examined. The expression of CCL2 and CCR2 mRNA in the spinal cord was detected by RT-PCR. Results: Compared with the model group, oxymatrine effectively delayed the onset time of EAE rats, significantly reduced the score of clinical neurological function (P <0.01), and improved the inflammatory infiltration of central nervous system (P <0.01) and myelin (P <0.01), and decreased the expression of CCL2 and CCR2 mRNA in the spinal cord (P <0.01, P <0.01). Conclusion: Oxymatrine has preventive and therapeutic effects on EAE rats and its mechanism may be related to the down-regulation of CCL2 and CCR2 mRNA in the spinal cord.