Immunomodulatory effects of the alkaloid sinomenine in the high responder ACI-to-Lewis cardiac allograft model
Immunomodulatory effects of the alkaloid sinomenine in the high responder ACI-to-Lewis cardiac allograft model
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DOI：
10.1097/00007890-199612270-00030
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发表时间：
1996-12-27
期刊：
影响因子：
6.2
通讯作者：
Hancock, WW
中科院分区：
文献类型：
--
作者：
Candinas, D;Mark, W;Hancock, WW
青风藤的提取物自古以来就被安全地用于治疗风湿性疾病的中药中，而纯化的生物碱青藤碱最近被证明具有抗炎和抗风湿作用。本研究描述了青藤碱在高反应ACI->刘易斯心脏移植模型中的作用，在该模型中移植后5天发生同种异体排斥反应。用青藤碱（15-30 mg/kg/天i. p.）或亚治疗剂量的环孢霉素（CsA，1.5mg/kg/天，i. m.）仅略微延长了同种异体移植物的存活时间（平均存活时间分别为5.4和7.8天）。而青藤碱与CsA联合应用则有显著的协同作用，平均生存期为42.2天（P < 0.001）。在第5天从接受青藤碱或CsA治疗的受者中收获的同种异体移植物显示致密的单核细胞浸润，伴有广泛的心外膜下梗死、水肿和微血管血小板和纤维蛋白沉积。免疫组织学分析显示，移植物内白细胞由>75%的巨噬细胞组成，其具有类似于10-20%的巨噬细胞和标记IL-2（类似于10%）、IFN-γ（10-20%）以及TNF-α（>50%）和iNOS（>50%），但只有低水平的IL-4或IL-10（
Extracts of the plant Sinomenium acutum have been used safely since ancient times in Chinese medicine for treatment of rheumatic diseases, and the purified alkaloid, sinomenine, was recently shown to have anti-inflammatory and antirheumatic effects. This study describes the effects of sinomenine in the high responder ACI-->Lewis cardiac transplant model in which allograft rejection occurred at 5 days posttransplant. Treatment with sinomenine (15-30 mg/kg/day i.p.) or a subtherapeutic dose of cyclosporine (CsA, 1.5 mg/kg/day, i.m.) prolonged allograft survival only marginally (mean survival 5.4 and 7.8 days, respectively). In contrast, the combination of sinomenine and CsA had a statistically significant synergistic effect, with a mean survival of 42.2 days (P < 0.001). Allografts harvested at day 5 from recipients treated with either sinomenine or CsA showed dense mononuclear cell infiltrates with widespread subepicardial infarcts, edema, and microvascular platelet and fibrin deposition. Immunohistologic analysis showed that intragraft leukocytes consisted of >75% macrophages with similar to 10-20%) and labeling for IL-2 (similar to 10%), and IFN-gamma (10-20%), as well as TNF-alpha (>50%) and iNOS (>50%), but only low levels of IL-4 or IL-10 (