目的 探讨干姜干热药性的药理特点及对低温冻伤的保护作用。方法 以甲状腺功能评价为研究内容，建立低温冻伤小鼠模型（−20±1）℃，通过形态学与分子生物学等手段评价干姜醇提物对小鼠低温冻伤的保护作用，通过系统药理学方法筛选出活性成分与关键靶标。建立体外人甲状腺乳头状癌BCPAP细胞氧化损伤模型并评价相关活性分子的保护作用。结果 系统药理方法筛选出姜黄素等代表性成药分子，预测靶标富集在甲状腺激素信号通路、FoxO通路等5条信号通路。干姜醇提物显著延长低温冻伤小鼠的生存时间，升高血清中游离三碘甲状腺原氨酸（free triiodothyronine，FT3）和游离甲状腺素（free thyroxine，FT4）水平（P＜0.05、0.01），上调小鼠甲状腺功能相关基因钠/碘协同转运蛋白（sodium/iodide cotransporter，Nis）、甲状腺过氧化物酶（thyroid peroxidase，Tpo）、甲状腺球蛋白（thyroglobulin，Tg）mRNA表达水平（P＜0.01），下调促甲状腺素受体（thyroid stimulating hormone receptor，Tshr）mRNA表达水平（P＜0.01），改善低温导致的甲状腺滤泡破损。体外实验发现干姜代表成分姜黄素、6-姜酚对H₂O₂诱导的BCPAP细胞损伤有显著保护作用（P＜0.05、0.01）。结论 干姜及其活性成分姜黄素、6-姜酚能够通过抗甲状腺氧化应激、促甲状腺功能从而保护小鼠低温冻伤。

Objective To explore the pharmacological characteristics of dry heat properties of Ganjiang (Zingiberis Rhizoma) and its protective effect on low temperature frostbite. Methods Taking the evaluation of thyroid function as the research content, a low-temperature frostbite mouse model (−20 ±1)℃ was established, and protective effect of Zingiberis Rhizoma alcohol extract on low-temperature frostbite in mice was evaluated by means of morphology and molecular biology. The active ingredients and key targets were screened out by chemical methods. An in vitro human papillary thyroid carcinoma BCPAP cell model of oxidative damage was established to evaluate the protective effect of related active molecules. Results The representative drug molecules such as curcumin were screened out by systematic pharmacological method, and predicted targets were enriched in five signaling pathways including thyroid hormone signaling pathway and FoxO pathway. Zingiberis Rhizoma alcohol extract significantly prolonged the survival time of low-temperature frostbite mice, increased levels of free triiodothyronine (FT3) and free thyroxine (FT4) in serum (P < 0.05, 0.01), up-regulated thyroid function-related genes sodium/iodide cotransporter (Nis), thyroid peroxidase (Tpo), and thyroglobulin (Tg) mRNA expression levels in mice (P < 0.01), down-regulated thyroid stimulating hormone receptor (Tshr) mRNA expression level (P < 0.01), improved the damage of thyroid follicles caused by hypothermia. In vitro experiments found that curcumin and 6-gingerol, the representative components of Zingiberis Rhizoma, had significant protective effects on H₂O₂-induced BCPAP cell injury (P < 0.05, 0.01). Conclusion Zingiberis Rhizoma and its active components, curcumin and 6-gingerol, can protect mice from low temperature frostbite by resisting thyroid oxidative stress and promoting thyroid function.

R285.5

国家自然科学基金资助项目（U1603122）；新疆生产建设兵团创新领域中青年领军人才项目（2018CB019）