目的 探讨乌药挥发油对寒凝气滞血瘀证大鼠中医证候积分、血液流变学及一氧化氮（nitric oxide，NO）-可溶性鸟苷酸环化酶（soluble guanylate cyclase，sGC）-环磷酸鸟苷（cyclic guanosine monophosphate，cGMP）信号通路的影响。方法 将48只SD雄性大鼠随机分为对照组、模型组及乌药挥发油高、中、低剂量（3.76、1.88、0.94 g/kg）组和复方丹参片（1.20 g/kg）组，每组8只。除对照组外，其余组大鼠采用sc肾上腺素加冰水浴双因素复合刺激14 d制备寒凝气滞血瘀证模型。从造模第15天开始，各给药组ig相应药物，对照组和模型组ig等体积2%聚山梨酯-80溶液，1次/d，连续7 d；在给药过程中间隔2 d给予1次造模条件，维持大鼠血瘀证表现。末次给药后的第2天对各组大鼠进行中医证候评分，测定各组大鼠血液流变学及血浆NO、内皮素（endothelin，ET）水平；采用苏木素-伊红（HE）染色法观察胸主动脉组织形态；采用ELISA法检测胸主动脉组织中环磷酸腺苷（cyclic adenosine monophosphate，cAMP）和cGMP水平；采用Western blotting法检测胸主动脉组织磷酸二酯酶5A（phosphodiesterase 5A，PDE5A）和sGC蛋白表达情况。结果 与对照组比较，模型组大鼠中医证候积分、血液流变学（全血黏度、血浆黏度、红细胞聚集指数、纤维蛋白原）、血浆ET含量、胸主动脉cAMP、cGMP含量、PDE5A蛋白表达水平均显著升高（P＜0.01）；血浆NO含量和胸主动脉sGC蛋白表达水平显著降低（P＜0.01）。与模型组比较，乌药挥发油组大鼠血液流变学指标和胸主动脉PDE5A蛋白表达水平显著降低（P＜0.05、0.01），血浆NO含量、胸主动脉cAMP和cGMP水平、sGC蛋白表达水平显著升高（P＜0.05、0.01）。大鼠胸主动脉HE染色显示，模型组大鼠血管内膜损伤明显、血管内皮细胞不完整、血管平滑肌细胞呈螺旋收缩样改变；乌药挥发油组大鼠血管内膜和血管内皮细胞损伤、血管平滑肌收缩显著改善。结论 乌药挥发油能有效改善寒凝气滞血瘀证大鼠中医证候评分、血液流变学，发挥血管内皮细胞保护、改善血液高凝状态的作用，其机制与调控NO-sGC-cGMP信号通路有关。

Objective To observe the effect of volatile oil from Wuyao (Linderae Radix) on hemorheology and nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway in rats with cold qi stagnation and blood stasis syndrome (QSBSS). Methods Forty-eight SD male rats were randomly divided into control group, model group, volatile oil from Linderae Radix high-, medium-, low-dose (3.76, 1.88, 0.94 g/kg) groups and Fufangdanshen tablets (1.2 g/g) group, with eight rats in each group. Except control group, rats of QSBSS model were prepared by two-factor stimulation of sc adrenaline plus ice water bath for 14 d. Starting from the 15th day of modeling, each administration group was ig corresponding drug, control group and model group were ig 2% tween-80 solution, once a day for 7 d. During the administration process, the modeling condition was given once at an interval of 2 d to maintain the manifestation of blood stasis in rats. On the 2nd day after the last administration, rats in each group were scored for TCM syndromes, and hemorheology, plasma NO and endothelin (ET) levels of rats in each group were determined; Hematoxylin-eosin (HE) staining was used to observe the morphology of thoracic aorta; Levels of cyclic adenosine monophosphate (cAMP) and cGMP in thoracic aortic tissues were determined by ELISA; Phosphodiesterase 5A (PDE5A) and sGC protein expressions in thoracic aortic tissues were detected by Western blotting. Results Compared with control group, TCM syndrome score, blood rheology (whole blood viscosity, plasma viscosity, erythrocyte aggregation index, fibrinogen), plasma ET level, PDE5A protein expression in thoracic aorta were significantly higher in model group (P < 0.01), plasma NO levels, cAMP and cGMP contents, sGC protein expression in thoracic aorta were significantly lower (P < 0.01). Compared with model group, rats in volatile oil from Linderae Radix group showed lower TCM syndrome score, blood rheological indexes, plasma ET levels, PDE5A protein expression in thoracic aorta (P < 0.05, 0.01), while significantly higher plasma NO levels, cAMP and cGMP contents, sGC protein expression in thoracic aorta (P < 0.05, 0.01). HE staining of rat thoracic aorta showed that vascular intima of rats in model group was significantly damaged, vascular endothelial cells were incomplete, and vascular smooth muscle cells showed spiral contraction-like changes. The damage of vascular intima and vascular endothelial cells, contraction of vascular smooth muscle were significantly improved in volatile oil from Linderae Radix group. Conclusion Volatile oil from Linderae Radix can effectively improve the TCM syndrome score and blood rheology in rats with QSBSS, and exert the effect of vascular endothelial cell protection and improving blood hypercoagulation, and its mechanism is related to the regulation of NO-sGC-cGMP signaling pathway.

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湖南省自然科学基金资助项目(2018JJ6040,2020JJ5434);湖南省中医药科研计划项目(201986,2021016);湖南省教育厅重点项目(19A372);湖南中医药大学药学一流学科开放基金资助项目(2018YX05)