目的 探讨巴曲酶对缺血性眩晕大鼠眩晕症状、抗氧化指标、炎症因子、血液流变学指标及脑组织NF-E2-相关因子2/血红素氧合酶1（Nrf2/HO-1）信号通路的影响。方法 40只SD大鼠随机分为假手术组、模型组、巴曲酶组（尾iv 1 BU/kg）、NRF2抑制剂（ML385）组（ip 30 mg/kg）、巴曲酶+ML385组（尾iv 1 BU/kg巴曲酶后ip 30 mg/kg ML385），每组8只，除假手术组外，其余各组大鼠均通过结扎右侧颈动脉及右侧锁骨下动脉构建缺血性眩晕大鼠模型，造模成功后按照各组给药方式进行给药处理，持续1周。全自动血液流变分析仪检测各组大鼠血液流变学指标，眩晕实验测定各组大鼠眩晕症状的变化程度；苏木精-伊红染色（HE）检测大鼠脑组织病理变化；酶联免疫吸附（ELISA）试剂盒检测大鼠血清一氧化氮（NO）、内毒素（ET），脑组织肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、超氧化物歧化酶（SOD）、丙二醛（MDA）水平；蛋白免疫印迹（WB）法检测大鼠脑组织中Nrf2/HO-1通路蛋白表达。结果 与假手术组相比，模型组大鼠跳台逃避潜伏期显著延长，眩晕症状、脑组织神经细胞受损严重，血液流变学指标，血清NO和ET水平，脑组织中TNF-α、IL-1β、MDA水平显著升高，SOD水平及Nrf2、HO-1蛋白表达显著降低。与模型组相比，巴曲酶组大鼠眩晕症状、脑组织神经细胞受损得到缓解，血液流变学指标、血清NO和ET水平、脑组织中TNF-α、IL-1β、MDA水平显著降低，脑组织SOD水平及Nrf2、HO-1蛋白表达显著升高；ML385组大鼠眩晕症状及各项指标与模型组变化趋势相似且更严重；与巴曲酶组相比，巴曲酶＋ML385组大鼠眩晕症状、脑组织神经细胞受损严重，血液流变学指标，血清NO和ET水平，脑组织中TNF-α、IL-1β、MDA水平显著升高，SOD水平及Nrf2、HO-1蛋白表达显著降低。结论 巴曲酶可能通过改善血液流变学、提高抗氧化能力、抑制炎症因子分泌及启动Nrf2/HO-1通路发挥对缺血性眩晕的保护作用。

Objective To investigate the effect of batroxobin on vertigo symptoms, antioxidant indicators, inflammatory factors, blood rheological indicators, and Nrf2/HO-1 signaling pathway in the brain of ischemic vertigo rats. Methods Forty Sprague Dawley rats were randomly divided into sham operation group, model group, batroxobin group (tail vein injection of 1 BU/kg), ML385 group (intraperitoneal injection of 30 mg/kg), batroxobin + ML385 group (intraperitoneal injection of 30 mg/kg ML385 after intravenous injection of 1 BU/kg batroxobin), with 8 rats in each group, except the sham operation group, the other groups of rats were ligated right carotid artery and right subclavian artery to build ischemic vertigo rat model. After successful modeling, the rats were given drugs according to the way of administration in each group, lasting for 1 week. The indexes of hemorheology were detected by automatic hemorheology analyzer, and the severity of vertigo was measured by vertigo test; the pathological changes of brain tissue were detected by hematoxylin eosin staining (HE); the levels of serum NO, ET, TNF-α, IL-1β, SOD, and MDA were detected by enzyme-linked immunosorbent assay (ELISA), the expression of Nrf2/HO-1 pathway proteins was detected by Western blot. Results Compared with the sham operation group, the escape latency of the model group was significantly extended, the symptoms of vertigo and the damage of nerve cells in brain tissue were serious, hemorheological parameters, levels of NO, ET in serum, levels of TNF-α, IL-1β and MDA in brain tissue were significantly increased, but the level of SOD, expression of Nrf2 and HO-1 protein were significantly decreased. Compared with the model group, the symptoms of vertigo and the damage of nerve cells in brain tissue were alleviated in batroxobin group, hemorheological parameters, levels of NO, ET in serum, levels of TNF-α, IL-1β and MDA in brain tissue were significantly decreased, the levels of SOD, expression of Nrf2 and HO-1 protein were significantly increased. In ML385 group, the symptoms of vertigo and nerve cell damage were serious, hemorheological parameters, levels of NO, ET in serum, levels of TNF-α, IL-1β and MDA in brain tissue were significantly increased, but the levels of SOD, expression of Nrf2 and HO-1 protein were significantly decreased. Compared with batroxobin group, vertigo symptoms and damaged nerve cells in brain tissue in batroxobin + ML385 group were more severe, hemorheological parameters, levels of NO, ET in serum, levels of TNF-α, IL-1β and MDA in brain tissue were significantly increased, level of SOD, expression of Nrf2 and HO-1 protein were significantly decreased. Conclusion Batroxobin may protect ischemic vertigo by improve blood rheology, improve antioxidant ability, inhibit the secretion of inflammatory factors and activating Nrf2/HO-1 pathway.

R965

河南省中医药科学研究专项课题（2019ZY3035）