目的 探討巴曲酶對缺血性眩暈大鼠眩暈癥狀、抗氧化指標(biāo)、炎癥因子、血液流變學(xué)指標(biāo)及腦組織NF-E2-相關(guān)因子2/血紅素氧合酶1（Nrf2/HO-1）信號通路的影響。方法 40只SD大鼠隨機(jī)分為假手術(shù)組、模型組、巴曲酶組（尾iv 1 BU/kg）、NRF2抑制劑（ML385）組（ip 30 mg/kg）、巴曲酶+ML385組（尾iv 1 BU/kg巴曲酶后ip 30 mg/kg ML385），每組8只，除假手術(shù)組外，其余各組大鼠均通過結(jié)扎右側(cè)頸動脈及右側(cè)鎖骨下動脈構(gòu)建缺血性眩暈大鼠模型，造模成功后按照各組給藥方式進(jìn)行給藥處理，持續(xù)1周。全自動血液流變分析儀檢測各組大鼠血液流變學(xué)指標(biāo)，眩暈實(shí)驗(yàn)測定各組大鼠眩暈癥狀的變化程度；蘇木精-伊紅染色（HE）檢測大鼠腦組織病理變化；酶聯(lián)免疫吸附（ELISA）試劑盒檢測大鼠血清一氧化氮（NO）、內(nèi)毒素（ET），腦組織腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素-1β（IL-1β）、超氧化物歧化酶（SOD）、丙二醛（MDA）水平；蛋白免疫印跡（WB）法檢測大鼠腦組織中Nrf2/HO-1通路蛋白表達(dá)。結(jié)果 與假手術(shù)組相比，模型組大鼠跳臺逃避潛伏期顯著延長，眩暈癥狀、腦組織神經(jīng)細(xì)胞受損嚴(yán)重，血液流變學(xué)指標(biāo)，血清NO和ET水平，腦組織中TNF-α、IL-1β、MDA水平顯著升高，SOD水平及Nrf2、HO-1蛋白表達(dá)顯著降低。與模型組相比，巴曲酶組大鼠眩暈癥狀、腦組織神經(jīng)細(xì)胞受損得到緩解，血液流變學(xué)指標(biāo)、血清NO和ET水平、腦組織中TNF-α、IL-1β、MDA水平顯著降低，腦組織SOD水平及Nrf2、HO-1蛋白表達(dá)顯著升高；ML385組大鼠眩暈癥狀及各項(xiàng)指標(biāo)與模型組變化趨勢相似且更嚴(yán)重；與巴曲酶組相比，巴曲酶＋ML385組大鼠眩暈癥狀、腦組織神經(jīng)細(xì)胞受損嚴(yán)重，血液流變學(xué)指標(biāo)，血清NO和ET水平，腦組織中TNF-α、IL-1β、MDA水平顯著升高，SOD水平及Nrf2、HO-1蛋白表達(dá)顯著降低。結(jié)論 巴曲酶可能通過改善血液流變學(xué)、提高抗氧化能力、抑制炎癥因子分泌及啟動Nrf2/HO-1通路發(fā)揮對缺血性眩暈的保護(hù)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

河南省中醫(yī)藥科學(xué)研究專項(xiàng)課題（2019ZY3035）