苦参素对实验性自身免疫性脑脊髓炎大鼠MMP-9、ICAM-1、HO-1表达的影响

目的: 通过检测实验性自身免疫性脑脊髓炎(EAE)模型脊髓中MMP-9、ICAM-1、HO-1的mRNA表达来研究苦参素对EAE的治疗作用。方法: 选取40只大鼠随机分为EAE组、空白对照组、苦参素低剂量组和苦参素高剂量组。EAE组和苦参素两个剂量组注射豚鼠全脊髓匀浆(GPSCH)抗原乳剂免疫建立EAE模型。苦参素两个剂量组于免疫当天起鼠尾静脉注射苦参素注射液200 mg·kg^-1和100 mg·kg^-1。观察3组大鼠的发病情况, 采用5分评分法对症状进行评分。设计和合成三条针对MMP-9、ICAM-1、HO-1mRNA的特异性引物, 采用PCR技术检测苦参素治疗16 d后大鼠脊髓中MMP-9、ICAM-1、HO-1mRNA的表达。结果: EAE组平均症状评分(2.45±0.36)高于苦参素治疗组(1.35±0.21), 且两者之间存在显著性差异(P<0.05)。与空白对照组比较, EAE组大鼠脊髓中MMP-9、ICAM-1的表达显著升高(P<0.01), 而苦参素治疗组中MMP-9、ICAM-1的表达与EAE组比较有所降低(P<0.05)。与空白对照组比较, EAE组大鼠脊髓中HO-1的表达显著降低(P<0.05), 而苦参素治疗组中HO-1的表达显著升高(P<0.01)。结论: 苦参素能够通过降低MMP-9和ICAM-1mRNA的表达, 并促进HO-1mRNA的表达而发挥对实验性自身免疫性脑脊髓炎的治疗作用。

Effects of oxymatrine on expression of MMP-9, ICAM-1 and HO-1 in rats with experimental autoimmune encephalomyelitis

OBJECTIVE To investigate protective effects of oxymatrine to experimental autoimmune encephalomyelitis by detecting expression of MMP-9, ICAM-1 and HO-1 mRNA. METHODS Forty rats were randomly divided into EAE group, control group, high oxymatrine dose group and low oxymatrine dose group. EAE group and oxymatrine groups were immunized with GPSCH as an antigen for oxymatrine EAE model. Rats in oxymatrine groups were treated with 200 mg·kg^-1 and 100 mg·kg^-1 oxymatrine for 16 days. Incidence of autoimmune encephalomyelitis was observed in these three groups and 5 points score for symptom was adopted to evaluate animal models. Primers were designed and synthesized to detect expression of MMP-9, ICAM-1 and HO-1 in cerebral tissues.RESULTS Symptom score of EAE group was (2.45±0.36), with significant differences from oxymatrine groups (1.35±0.21). Compared with control group, expression of MMP-9 and ICAM-1 mRNA was higher in EAE group but lower in oxymatrine group, and the two groups had significant difference (P<0.05).CONCLUSION Protective effects of oxymatrine to experimental autoimmune encephalomyelitis may be achieved by decreasing levels of MMP-9 and ICAM-1mRNA, and increasing level of HO-1.