目的研究灵芝双向发酵对雷公藤的解毒持效作用。方法运用双向发酵工程的原理和方法获得灵雷菌质（G30）,用常规急性毒性试验、免疫学试验、自身免疫疾病动物模型试验等进行G30的毒性和药效学研究。结果G30的LD₅₀较雷公藤生药组显著提高,并且能抑制小鼠T、B淋巴细胞的增殖和血清溶血素的分泌;G30降低阿霉素诱导的肾炎大鼠的24 h尿蛋白量,同时改善肾炎大鼠的多项生化指标,且对各脏器的毒性要小于雷公藤生药;G30缓解佐剂性类风湿关节炎大鼠的足肿胀度,并改善大鼠的生存状况。结论灵芝与雷公藤构成发酵组合所产灵雷菌质G30毒性降低并仍然保持免疫抑制作用,对佐剂性类风湿关节炎及阿霉素诱导的大鼠肾炎均有一定的治疗作用。显示双向发酵对雷公藤解毒持效是一条可行的途径。

Objective To survey the toxicity-reducing and efficacy-maintaining function of fungal fer-mentative products in Tripterygium wilfordii by Ganoderma lucidum bi-direction solid fermentation.Methods Bi-direction solid fermentation engineering was applied and Linglei fungal substance (G30)wasobtained, Its toxicity and pharmacodynamics were detected with regular acute toxicity test，immunologicaltest，and tests on autoimmune disease animal pattern. Results LD⁵⁰ of G30 was higher than that of crude击ug. G30 had the inhibiting effect on proliferation of both T and B lymphocytes and could decrease theproduction of hemolysin in mice. G30 could decrease 24 h urine protein of nephritis model of rats caused byAdriamycin，and it had less toxicity on organs than T.wil fordii. G30 could alleviate foot swelling ofrheumatoid arthritis model. Conclusion Linglei fungal substance is obtained from the fermentative compo-sition of G. lucidum fungal and T. wilfordii, It shows low toxicity and effects of immunosuppression andalso has some therapeutic effects on the model of autoimmune diseases. The pharmocological effects sug-gest that the bi-directional fermentation engineering may possibly provide a new way to prepare the toxici-ty-reducing and efficacy-maintaining function of fungal fermentative products in T. wilfordii.

科技部国际合作项目(与美国马里兰大学)“雷公藤固体发酵减毒持效的研究”(2006DFA33060);“973”课题(2009CB522801);江西省科技攻关项目;南昌市科技局攻关项目