咖啡因对大鼠实验性自身免疫性脑脊髓炎的干预作用及机制探讨

Neuroprotective effect of caffeine on experimental autoimmune encephalomyelitis in rats

目的探讨咖啡因对大鼠实验性自身性免疫性脑脊髓炎（EAE）的干预作用及其药理作用机制。方法将40只雌性Wistar大鼠随机分为空白对照组、EAE模型组、咖啡因10mg／kg组、咖啡因30mg／kg组，后3组制作EAE模型，于足垫皮下注射豚鼠脊髓匀浆（GPSCH）-完全弗氏佐剂（CFA）乳剂。激发自身免疫反应，咖啡因10、30mg／kg组于免疫前7d开始和免疫后一直饮用咖啡因。观察并评估动物的运动神经功能和中枢神经组织病理变化，采用RT—PCR法检测发病高峰期颈髓TNF—α、TGF-β1和腺苷A1、A2A受体mRNA的表达水平。结果与EAE模型组相比，咖啡因10、30mg／kg组发病率虽降低，但差异无统计学意义（P〉0．05），神经症状评分明显减低（P〈0．05），炎症细胞浸润和髓鞘脱失程度明显减轻，TNF—a的mRNA表达水平明显下降（P〈0．05），TGF—β1的mRNA表达水平明显升高（P〈0．05或0．01）。结论低剂量的咖啡因（10、30mg／kg）能减轻EAE的病情和中枢神经组织的炎症病理改变，其神经保护作用很可能是通过上调A1受体水平从而调控中枢炎症反应来实现的。

Objective To investigate the effect of caffeine on experimental autoimmune encephalomyetiti s （EAE） in rats. Methods Forty female Wistar rats were randomly divided into four groups：（1）control group, （2）EAE group, （3）10mg/kg caffeine group,（ 4）30mg/kg caffeine group. EAE model was induced by injecting guinea pig spinal cord homogenate （GPSCH） with complete Freud＇s adjuvant （CFA）into soles of rats （groups 2, 3,4）; 10mg/kg （group3） or 30mg/kg （group4） was given to rats in drinking water starting from 7d before and continuously after EAE model induced. Results The symptom and histology scores were compared among groups by methods of quantization. The expressions of TNF-α, TGF-β1, adenosine A1 and A2A receptors mRNAs in spinal cord were examined by RT-PCR. Results There were no significant differences in incidence of EAE between EAE and two caffeine groups（P 〉0.05）. The max symptom score of two caffeine groups was lower than that of EAE group（P〈0.05）. EAE group showed more severe infiltration of inflammatory cells and demyelination than two caffeine groups. The expression of TNF-α mRNA in caffeine groups was lower and the expression of TGF-β1 mRNA was higher than that in EAE group（P〈0.05 or 0.01）. Conclusion Low dose caffeine（10mg/kg, 30mg/kg） treatment can reduce max neurological score and pathological changes of EAE, which may be related to increasing adenosine A1 receptor.