钙激活中性蛋白酶抑制剂对实验性自身免疫性脑脊髓炎的保护作用

目的　建立豚鼠实验性自身免疫性脑脊髓炎 ( EAE)病理模型 ,研究钙激活中性蛋白酶 ( calpain)对 EAE的作用。方法　将牛脊髓匀浆与等量完全福 (氏 )佐剂充分混合 ,注射于豚鼠后肢足底诱发 EAE。发病豚鼠分别注射 calpain抑制剂与地塞米松 ,观察其对 EAE临床症状及病理变化的影响。结果　模型组豚鼠免疫致敏后相继出现明显的 EAE症状 ,表现为行动困难 ,摄食减少 ,体重进行性下降 ,肢体瘫痪 ,发病率为 87.5 % ( 2 8/3 2 )。豚鼠注射 calpain抑制剂后可观察到脱髓鞘病变明显减轻 ,神经元丢失减少 ,但炎性细胞浸润仍然存在。结论　calpain参与了 EAE的神经病理损伤过程 ,calpain抑制剂对 EAE有一定保护作用

Calpain Inhibitor Has a Protective Effect on Experimental Autoimmune Encephalomyelitis in Guinea Pigs

Objective To establish experimental autoimmune encephalomyelitis (EAE) model in guinea pigs and evaluate the effect of calpain inhibitor on EAE. Methods The fresh bovine spinal cord was used as the antigen to induce the EAE model in guinea pigs. The changes in their body weights and the paralysis symptoms were observed, the pathological syndrome was then estimated according to the score of EAE. The guinea pigs scored between 3 5 were divided into three groups.In group 1 and 2,calpain inhibitor and dexamethasone was injected respectively. Then histological changes in peripheral nerves, spinal cord and brain were examined 30 days after sensitization. Results 28/32 of model animals exhibited distinct clinical EAE symptoms,such as the loss of body weight, acting slowly and paralysis of the limbs. Calpain inhibitor i.p. after sensitization significantly ameliorated the symptom and histopathology in spinal cord and sciatic nerve.It reduced the loss of neuron but focal accumulations of lymphocytes as well as other mononuclear cells around small blood vessels could still be found. Conclusions The results indicate that calpain inhibitor has a protective effect on EAE development in guinea pigs.