目的 以药食两用调血脂中药山楂Crataegi Fructus、泽泻Alismatis Rhizoma和决明子Cassiae Semen等为培养基组分,以实验室筛选的产洛伐他汀(Lovastatin)的红曲霉Monascus purpureus为菌种,对制备既含有传统中药降脂成分又含有他汀类降脂药物的天然降脂中药的固态发酵工艺进行探索与研究。方法 通过单因素试验和正交试验优化固态发酵工艺,用TLC和HPLC分析方法对发酵产物有效成分进行定性和定量分析。结果 实验获得的混合发酵制备调血脂中药优化工艺条件为500 mL三角瓶装量100 g固态培养基,接种培养48 h的液态种子10 mL,30 ℃恒温培养2 d后,打散培养基,第3天加入培养基干基质24%的无菌水,5 d后温度降至25 ℃继续培养至18 d,洛伐他汀产量可达5.127 mg/g,较优化前提高124.8%。TLC和HPLC分析结果显示:与大米红曲比较,获得中药红曲发酵产物含有更多有效成分,洛伐他汀产量提高42.27%,但γ-氨基丁酸产量下降17.89%;与未发酵基质比较,中药发酵产物中中药的有效成分熊果酸、2,3-乙酰泽泻醇-B、大黄酚和大黄素甲醚分别提高了232.7%、173.7%、767.6%和888.4%。结论 山楂、泽泻和决明子经红曲霉菌固态发酵后,除能显著提高调血脂有效成分的量外,还能提高中药有效成分的量,获得的调血脂中药发酵工艺具有一定的实际应用价值。

Objective To obtain a new lipid-lowering product that combines the advantages of lipid-lowering Chinese materia medica (CMM) and statin drugs. Solid-state fermentation was studied using medicinal and edible CMM as media components, Lovastatin yielding monascus screened in our laboratory was used as strain and Lovastatin yielding was used as index. Methods Solid-state fermentation was optimized by single factor and orthogonal test, qualitative and quantitative analysis was conducted of the product via TLC and HPLC. Results The optimal fermentation conditions contained 100 g/solid medium in 500 mL flask bottling capacity, material thickness of 2.5 cm, 10 mL liquid seed of 48 h, 10% inoculation volume, incubating at 30 ℃, breaking up the medium on day 2, adding 24% sterile water on day 3, cooling to 25 ℃ and culturing for 18 d in total, and Lovastatin yielding was up to 5.127 mg/g. Fermentation product of CMM contained more components compared with that without medicines, Lovastatin yielding increased by 42.27%, but γ- aminobutyric acid yielding decreased by 17.89%. Contents of main active ingredients ursolic acid, 2,3-acetyl alisol-B, chrysophanol, and physcion were increased by 232.7%, 173.7%, 767.6%, and 888.4%. Conclusion Active ingredients of hawthorn, alisma, and cassia are released into the products after fermentation and contents of lipid-lowering active ingredients were improved significantly, new active ingredients are also noticed. Therefore, the fermentation process of lipid-lowering medicines obtained in this experimental study has some practical values.

四川省科技支撑项目资助(2012FZ0048);成都市科学技术局科技惠民技术研发项目(2015-HM01-00047-SF)