目的 探究黄芩素、冰片及配伍对脑基底血管张力的影响和抗脑缺血后脑基底血管内皮功能障碍的作用及机制。方法 采用离体血管环实验分别考察累积浓度的黄芩素、冰片及不同比例配伍对静息状态和内皮素-1（endothelin-1，ET-1）、血栓素A₂类似物（U46619）、5-羟色胺（5-hydroxytryptamine，5-HT）预收缩的脑基底血管环张力的影响。利用线栓法构建局灶性脑缺血模型，给予不同比例的黄芩素-冰片，进行神经功能评分；采用红四氮唑（2，3，5-triphenyl tetrazolium chloride，TTC）染色观察脑梗死体积；荧光染色法观察缺血侧皮层CD34表达；检测缺血侧皮层一氧化氮（nitric oxide，NO）水平；苏木素-伊红（HE）染色观察脑基底动脉血管内皮完整性；Western blotting检测脑基底动脉内皮型一氧化氮合酶（endothelial nitric oxide synthase，eNOS）、诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）表达；ELISA法检测血清中炎性因子水平。结果 黄芩素、冰片和各比例配伍组对基础状态血管环张力无明显影响，但能明显舒张由ET-1、U46619、5-HT预收缩的脑基底血管环（P<0.05、0.01），且随着浓度增大，黄芩素-冰片（1∶3）对ET-1、U46619预收血管环的舒张作用具有明显的优势。大脑中动脉局灶性梗死（middle cerebral artery occlusion，MCAO）术后大鼠神经功能评分显著升高（P<0.01），药物干预24 h后，神经功能评分不同程度降低（P<0.01）；与假手术组比较，模型组大鼠脑梗死率显著升高（P<0.01），脑基底动脉内皮损伤严重、断裂，eNOS表达显著降低（P<0.05），iNOS表达显著升高（P<0.01），缺血侧皮层中CD34表达升高（P<0.01），NO水平显著降低（P<0.01），血清中白细胞介素-1β（interleukin-1β，IL-1β）、IL-6、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）水平明显升高（P<0.01），转化生长因子-β（transforming growth factor-β，TGF-β）水平明显降低（P<0.01）；而黄芩素-冰片能不同程度明显降低大鼠脑梗死率（P<0.01），改善脑基底动脉内皮状态，升高动脉中eNOS表达、缺血侧皮层中NO、CD34表达和血清中TGF-β表达（P<0.05、0.01），下调脑基底动脉中iNOS表达和血清中IL-1β、IL-6、TNF-α水平（P<0.05、0.01）。结论 黄芩素、冰片及配伍可抑制由ET-1、U46619和5-HT诱发的血管收缩，且黄芩素-冰片（1∶3）的舒张作用优于其余各组，其可抑制过度炎性反应，上调缺血后微血管eNOS表达，下调iNOS表达，促进NO合成和分泌，发挥抗缺血区微血管内皮功能障碍和促进恢复，改善微循环，减轻神经损伤的作用。

Objective To explore the effect and mechanism of baicalein, borneol and their combination on tension of cerebral basal vessels and their anti-endothelial dysfunction after cerebral ischemia. Methods In vitro vascular ring experiments was used to investigate the effects of cumulative concentrations of baicalein, borneol and different proportions of compatibility on tension of cerebral basal vascular ring pre-contracted by endothelin-1 (ET-1), thromboxane A₂ analog (U46619) and 5-hydroxytryptamine (5-HT) in resting state. A model of focal cerebral ischemia was constructed by thread occlusion method, different proportions of baicalein-borneol was given, neurological function score was performed; 2,3,5-Triphenyl tetrazolium chloride (TTC) staining was used to observe the volume of cerebral infarction; Fluorescence staining was used to observe the expression of CD34 in ischemic cortex; Level of nitric oxide (NO) in ischemic cortex was detected; Hematoxylin-eosin (HE) staining was used to observe the endothelial integrity of cerebral basal artery; Western blotting was used to detect the expressions of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) in basal artery of the brain; ELISA method was used to detect the levels of inflammatory factors in serum. Results The combination of baicalein, borneol and various proportions had no significant effect on basal vascular ring tension, but could significantly relax the brain basal vascular ring pre-contracted by ET-1, U46619 and 5-HT (P < 0.05, 0.01). As the concentration increased, baicalein-borneol (1:3) had a significant advantage in the relaxation effect of ET-1, U46619 pre-contracted vascular rings. After middle cerebral artery occlusion (MCAO) surgery, the neurological function score of rats was significantly increased (P < 0.01). After 24 h of drug intervention, the neurological function score was decreased to varying degrees (P < 0.01); Compared with sham group, cerebral infarction rate of rats in model group was significantly increased (P < 0.01), endothelial damage and rupture of cerebral basal artery were severe, eNOS expression was significantly decreased (P < 0.05), iNOS expression was significantly increased (P < 0.01), CD34 expression in ischemic cortex was increased (P < 0.01), NO level was significantly reduced (P < 0.01), levels of interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in serum were significantly increased (P < 0.01), transforming growth factor-β (TGF-β) level was significantly decreased (P < 0.01); Baicalein-borneol could significantly reduce the cerebral infarction rate to varying degrees (P < 0.01), improve the endothelial status of basal artery, increase the expressions of eNOS in arteries, NO and CD34 in ischemic cortex and TGF-β in serum (P < 0.05, 0.01), down-regulate iNOS expression in basal artery of brain and IL-1β, IL-6, TNF-α in serum (P < 0.05, 0.01). Conclusion Baicalein, borneol and their combination can inhibit vasoconstriction induced by ET-1, U46619 and 5-HT, and the relaxation effect of baicalein-borneol (1:3) is superior to other groups. It can inhibit excessive inflammatory response, upregulate the expression of eNOS in microvessels after ischemia, down-regulate the expression of iNOS, promote NO synthesis and secretion, and play a role in combating microvascular endothelial dysfunction and promoting recovery in ischemic areas, improving microcirculation and reducing nerve damage.

R285.5

陕西省教育厅专项科研计划项目（21JK0608）；陕西省中医药管理局中医药科研项目（2021-ZZ-JC023）