目的 探究紫草素（SK）对活性酵母诱导的血热证小鼠模型的清热凉血作用与血液氧化还原稳态调控的关系。方法 小鼠随机分为对照组、模型组、SK（10 mg/kg）组、阿司匹林（Asp，200 mg/kg）组、L-丁硫氨酸亚砜亚胺（BSO，600 mg/kg）组、N-乙酰-L-半胱氨酸（NAC，400 mg/kg）组、BSO联合SK组、NAC联合SK组。小鼠颈背部sc 0.2 g/mL活性酵母提取物（10 mL/kg），造模0.5 h后ip SK，造模8 h后ig Asp，于实验开始前ip BSO、NAC，2次/d，连续1周。考察小鼠肛温（t_R）、基本活动、代谢、凝血、血细胞计数等指标，采用OPA荧光法测定小鼠血清中还原型谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）水平。结果 与对照组相比，模型组小鼠造模4 h后t_R显著升高（P<0.05），10 h达到（38.07±0.11）℃；小鼠出现烦躁、口唇色红、喜饮、碳末推进率降低、粪便含水量降低、凝血时间延长现象（P<0.05）；肺组织红细胞、炎性细胞浸润；血清LPO、MDA水平显著升高、SOD活性降低、GSH/GSSG比率减小（P<0.05）。与模型组相比，SK组小鼠t_R显著降低，10 h达到（37.51±0.12）℃；各指标均得到显著改善；血清LPO、MDA水平降低、SOD活性升高、GSH/GSSG比率增大（P<0.05）。BSO组可降低血清GSH/GSSG比率（P<0.05），减弱SK对血热证小鼠的治疗作用；NAC组可增加血清GSH水平，增加GSH/GSSG比率（P<0.05），增强SK对血热证小鼠的治疗效果。结论 SK通过调控血液氧化还原稳态，缓解血热证小鼠高热、出血瘀血、血液氧化损伤，从而发挥清热凉血作用。

Objective To explore the relationship between clearing heat and cooling blood of shikonin (SK) and regulation of blood redox homeostasis in blood-heat syndrome mice model induced by active yeast. Methods Mice were randomly divided into control group, model group, SK (10 mg/kg) group, aspirin positive (200 mg/kg) group, L-buthionine sulfoximine (BSO, 600 mg/kg) group, N-acetyl-L-cysteine (NAC, 400 mg/kg) group, BSO combined with SK group, NAC combined with SK group. Mice were sc with 0.2 g/mL active yeast (10 mL/kg) on the neck, mice were ip SK at 0.5 h, ig Asp at 8 h, ip BSO and NAC before the beginning of the experiment (twice a day for one week). The rectal temperature (t_R), general activity, metabolism, coagulation, and blood cell counting were determined. The levels of GSH and GSSG were determined by OPA assay. Results Compared with the control group, t_R of mice was significantly increased at 4 h (P<0.05) and reached (38.07±0.11)℃ at 10 h in model group; Irritability, redder lips, inclined to drinking, reduced carbon powder propelling rate, decreased pellet moisture capacity and prolonged coagulation time were observed (P<0.05); RBC and inflammatory cells infiltrated were observed in lung tissue sections; The levels of LPO and MDA in serum were significantly increased, the activity of SOD was decreased, GSH/GSSG was decreased (P<0.05). Compared with model group, t_R of mice was significantly reduced and reached (37.51±0.12)℃ at 10 h in SK group; The symptoms were significantly attenuated; The level of LPO and MDA in serum were decreased; The activity of SOD and GSH/GSSG ratio were increased (P<0.05). BSO significantly reduced the GSH/GSSG ratio (P<0.05), reduced the effect of SK on blood-heat syndrome mice model. NAC increased the level of GSH in serum and GSH/GSSG ratio (P<0.05), enhanced the SK treatment effect. Conclusion SK can attenuate hyperpyrexia, hemorrhage and congestion, oxidative damage in blood-heat syndrome mice model by regulating the blood redox homeostasis, and thereby the effect of clearing heat and cooling blood work.

R285.5

国家自然科学基金资助项目（U1603122）；兵团科技创新领域中青年领军人才项目（2018CB019）；兵团英才项目（0320/CZ000601）