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蛋白酶抑制剂对实验性变应性脑脊髓炎抑制作用的观察

Observations on the effects of protease inhibitors on the suppression of experimental allergic encephalomyelitis.

作者信息

Smith M E, Amaducci L A

出版信息

Neurochem Res. 1982 May;7(5):541-54. doi: 10.1007/BF00965121.

DOI:10.1007/BF00965121
PMID:6750429
Abstract

Inhibitors of proteolytic enzymes were tested for their ability to suppress the clinical signs and CNS lesions produced by injection of purified myelin in complete Freund's adjuvant into Lewis rats. Pepstatin or a series of neutral protease inhibitors including aprotinin, soybean trypsin inhibitor, leupeptin, antipain, trans-aminomethyl cyclohexane carboxylic acid (AMCA), epsilon-amino caproic acid (EACA) nitrophenyl guanidino benzoate (NPGB), D- and L-polylysine, or a new commercial protease inhibitor, dipropionyl Rhein (DPR) were injected daily beginning on day 7 after immunization of rats with myelin. Aprotinin and soybean trypsin inhibitor exacerbated the symptoms and lesions of experimental allergic encephalomyelitis (EAE), leupeptin and antipain had no effect, and the plasminogen activators AMCA, EACA, NPGB, as well as poly-L- and poly-D-lysine and DPR suppressed various aspects of EAE. The measurement of acid protease as a biochemical method for quantitation of the degree of cellular infiltration into the CNS is proposed, and the results with the various treatments presented. AMCA and NPGB may exert their effects at the site of entrance of the lymphoid cells into the CNS.

摘要

测试了蛋白水解酶抑制剂抑制将纯化髓磷脂与完全弗氏佐剂注射到Lewis大鼠体内所产生的临床症状和中枢神经系统病变的能力。从用髓磷脂免疫大鼠后的第7天开始,每天注射胃蛋白酶抑制剂或一系列中性蛋白酶抑制剂,包括抑肽酶、大豆胰蛋白酶抑制剂、亮抑酶肽、抗痛素、反式氨甲基环己烷羧酸(AMCA)、ε-氨基己酸(EACA)、硝基苯基胍基苯甲酸酯(NPGB)、D-和L-聚赖氨酸,或一种新的商业蛋白酶抑制剂二丙酰大黄酸(DPR)。抑肽酶和大豆胰蛋白酶抑制剂加剧了实验性变态反应性脑脊髓炎(EAE)的症状和病变,亮抑酶肽和抗痛素没有效果,而纤溶酶原激活剂AMCA、EACA、NPGB以及聚-L-赖氨酸、聚-D-赖氨酸和DPR抑制了EAE的各个方面。提出将酸性蛋白酶的测定作为定量中枢神经系统细胞浸润程度的生化方法,并给出了各种治疗方法的结果。AMCA和NPGB可能在淋巴细胞进入中枢神经系统的入口部位发挥作用。

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