阿片δ受体拮抗剂Naltrindole对免疫排异反应的抑制作用  

EFFECT OF OPIOID RECEPTOR ANTAGONIST NALTRINDOLE ON TRANSPLANTATION REJECTION

作　　者：李怡凡[1] 许晓楠 梅林[1] 梁颖 丁桂凤[1] 范少光[1] 

机构地区：[1]北京医科大学生理学系

出　　处：《药学学报》1999年第6期424-427,共4页Acta Pharmaceutica Sinica

基　　金：卫生部基金

摘　　要：目的：观察选择性阿片δ受体拮抗剂纳曲酮（ｎａｌｔｒｅｘｏｎｅ）对移植排异反应的影响。方法：整体实验以小鼠异体异位心肌组织移植为模型，ｉｐｎａｌｔｒｉｎｄｏｌｅ或纳曲酮（５ｍｇ·ｋｇ－１，ｂｉｄ），观察移植心肌组织的存活时间；离体实验中，将两种不同品系小鼠淋巴细胞混合培养，观察ｎａｌｔｒｉｎｄｏｌｅ、纳曲酮或亮脑啡肽对淋巴细胞反应的影响。结果：Ｎａｌｔｒｉｎｄｏｌｅ可显著延长小鼠异体异位移植心肌组织的存活时间；并明显抑制混合淋巴细胞反应。Ｎａｌｔｒｉｎｄｏｌｅ的上述作用均较纳曲酮强。阿片δ受体激动剂亮脑啡肽（ＤＳｅｒ２Ｌｕｅｅｎｋｅｐｈａｌｉｎ）可以促进混合淋巴细胞反应。结论：阿片δ受体在移植免疫排异反应中起重要介导作用，ｎａｌｔｒｉｎｄｏｌｅ对此移植排异反应有明显抑制作用。AIM: To investigate the subtype of the opioid receptors involved in transplantation rejection. METHODS: The in vivo experiment: Cardiac tissue of the newborn KM mouse was transplanted into the ear of Balb/c mouse. The survival of the transplanted tissue was shown with its electrocardiogram. Naltrexone or naltrindole (selective opioid receptor antagonist) was injected ip twice per day for 10 days (5 mgkg-1 body weight). The in vitro experiment: Lymphocytes from two different strains of mice were mixed and cultured together. Naltrexone, naltrindole or enkephalin (a selective opioid receptor agonist) was added into the culture fluid. 3HTdR uptake (cpm) was measured to show the mixed lymphocyte reaction. RESULTS: The mean survival time of the transplanted tissues of naltrindoletreated group was 15624 days, which was significantly longer (ttest, P<005, n=6) than that of naltrexonetreated group (10911 days). While the latter was longer (ttest, P<005, n=6) than that of normal saline injection group (8005days) and control group (8109 days). The mixed lymphocyte reactions, after treated with naltrexone at concentration 10-8, 10-6 and 10-4 molL-1, were 3196810, 1268320 and 432110 min-1, respectively. The result showed an inhibitory effect of naltrexone on mixed lymphocyte reaction in dose response way. While the mixed lymphocyte reaction treated with naltrindole at concentrations 10-10, 10-8, 10-6 and 10-4 molL-1 were 2021101, 1611450, 630160 and 455105 min-1, which was significantly decreased(ANOVA, P<005) as compared with the naltrexone group. It was also found that enkephalin increased the mixed lymphocyte reaction at the early stage of culture. CONCLUSION: The results suggest that opioid receptor is involved in the antigeninduced immune reaction and the receptor antagonist naltrindole can i

关 键 词：阿片受体拮抗剂 纳曲酮 移植排异反应 

分 类 号：R979.5[医药卫生—药品] R392.4[医药卫生—药学]