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目的:观察苦参素对实验性自身免疫性脑脊髓炎(EAE)大鼠脊髓中Toll样受体-4(TLR4)和血清中髓样分化蛋白-2(MD-2)表达的影响,探讨苦参素对EAE大鼠的防治机制。方法:用豚鼠全脊髓匀浆和完全弗氏佐剂制成的抗原乳剂复制EAE模型,将50只大鼠随机分为正常组、模型组、苦参素高、中、低剂量组(250、200、150 mg/kg),连续给药16天,同期模型组和正常组腹腔注射等量生理盐水,观察记录大鼠体重变化,神经功能学评分,苏木素-伊红(HE)和变色酸2R-亮绿(C-2R-BG)染色观察病理改变、RT-PCR法检测脊髓中TLR4的表达、ELISA法测定EAE大鼠血清中MD-2含量的变化。结果:苦参素起效剂量为41.67mg/kg,半数致死量为353.5mg/kg,苦参素150、200、250mg/kg能延迟大鼠EAE的发病时间,明显降低EAE大鼠的神经功能学评分,减轻EAE大鼠中枢神经系统炎症浸润和髓鞘脱失,下调脊髓中TLR4的表达,降低血清中MD-2的含量,且高中低三剂量组间的差异有统计学意义。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TLR4和血清中和MD-2的表达有关。
Objective: To observe the effect of oxymatrine on the expression of TLR4 and MD-2 in the spinal cord of experimental autoimmune encephalomyelitis (EAE) rats Prevention and Cure Mechanism of Oxymatrine on EAE Rats. Methods: EAE model was replicated with guinea pig full spinal cord homogenate and complete Freund’s adjuvant. 50 rats were randomly divided into normal group, model group, high, medium and low dose oxymatrine group (250, 200, 150 mg / kg) for consecutive 16 days. At the same time, rats in model group and normal group were injected intraperitoneally with equal volume of normal saline. Body weight, neurological score, hematoxylin and eosin (HE) The expression of TLR4 in the spinal cord was detected by RT-PCR and the content of MD-2 in the serum of EAE rats by ELISA. Results: The effective dose of Oxymatrine was 41.67mg / kg and the lethal dose was 353.5mg / kg. Oxymatrine 150,200,250mg / kg could delay the onset of EAE and the neurological function of EAE rats Scoring, and relieve the inflammatory infiltration and demyelination of central nervous system in EAE rats, downregulate the expression of TLR4 in the spinal cord, decrease the content of MD-2 in serum, and there is significant difference between the high, middle and low dose groups. Conclusion: Oxymatrine has preventive and therapeutic effects on EAE rats, and its mechanism may be related to the down-regulation of TLR4 and MD-2 expression in the spinal cord of rats.