目的 探討布地奈德吸入給藥對(duì)慢性支氣管哮喘模型小鼠多形螺旋線蟲預(yù)警素釋放抑制劑/轉(zhuǎn)錄因子（HpARIh/STAT）信號(hào)通路的影響。方法 30只小鼠隨機(jī)分成3組，對(duì)照組、模型組和布地奈德組，每組10只。模型組小鼠于第1天和第14天用卵白蛋白（OVA）致敏，第24天開始霧化吸入1% OVA并持續(xù)刺激至第28天，建立哮喘氣道重塑模型；布地奈德組小鼠在吸入OVA 2 h前吸入布地奈德30 min；對(duì)照組使用生理鹽水代替OVA。第28天最后一次霧化結(jié)束后24 h處死小鼠，采用病理圖像分析系統(tǒng)測(cè)量小鼠的氣道形態(tài)學(xué)參數(shù)，分別取各組小鼠外周血和肺組織，用ELISA試劑盒檢測(cè)外周血上清液腫瘤壞死因子（TNF-α）、白細(xì)胞介素13（IL-13）和轉(zhuǎn)化生長(zhǎng)因子-β（TGF-β）水平，HE染色觀察肺組織病理學(xué)變化，Western blotting檢測(cè)肺組織蛋白HpARIh、IL-13、STAT3和STAT6的表達(dá)。結(jié)果 病理組織學(xué)結(jié)果顯示布地奈德組小鼠支氣管壁的炎性細(xì)胞浸潤(rùn)明顯減少，支氣管壁結(jié)構(gòu)改變明顯減輕。HE染色結(jié)果顯示布地奈德干預(yù)后有效地減少了炎性因子對(duì)肺組織的浸潤(rùn)。ELISA結(jié)果顯示布地奈德組與模型組相比，外周血上清中TNF-α、TGF-β和IL-13等炎癥因子水平明顯降低（P<0.05），但仍高于對(duì)照組。Western blotting結(jié)果表明布地奈德通過(guò)增加HpARIh蛋白表達(dá)來(lái)激活STAT3，同時(shí)抑制STAT6，從而抑制哮喘誘發(fā)因子IL-13的表達(dá)水平。結(jié)論 早期霧化吸入布地奈德可以有效抑制TNF-α、TGF-β和IL-13等炎癥因子的表達(dá)，同時(shí)通過(guò)激活HpARIh/STAT信號(hào)通路抑制IL-13的表達(dá)，明顯減輕哮喘小鼠的氣道重塑。

Objective To investigate the effect of budesonide on HpARIh/STAT signaling pathway in chronic bronchial asthma model mice. Metheds Thirty mice were randomly divided into three groups: normal control group, model group and budesonide group, with 10 rats in each group. Mice in model group were sensitized with ovalbumin (OVA) on day 1 and day 14, and aerosolized 1% OVA on day 24 and continued drug stimulation until day 28 to establish an asthmatic airway remodeling model; mice in budesonide group were inhaled budesonide 30 min before 2 h inhalation of OVA; mice in normal control group used physiological saline instead of OVA. On the 28th day, the mice were sacrificed 24 h after the last atomization. The pathological image analysis system was used to measure the airway morphological parameters of mice. Then the peripheral blood and lung tissues of mice in each group were taken, and the peripheral blood was detected by ELISA kit. The expression levels of tumor necrosis factor (TNF-α), interleukin-13 (IL-13) and transforming growth factor-β (TGF-β) were detected in the supernatant. HE staining was used to observe the pathological changes of lung tissue. Western blotting was used to detect protein expression of HpARIh, IL-13, STAT3 and STAT6 in lung tissue. Results Histopathological results showed that the inflammatory cell infiltration of the bronchial wall and the structural changes of the bronchial wall of mice in budesonide group were reduced significantly (P<0.05). HE staining results showed that the infiltration of inflammatory factors in lung tissue of mice in budesonide group were reduced (P<0.05). The results of ELISA showed that the levels of TNF-α, TGF-β and IL-13 in peripheral blood supernatant of mice in budesonide group were significantly lower than in model group (P<0.05), but still higher than control group. Results of Western blotting indicated that budesonide inhibited the expression of the asthma-inducible factor IL-13 by increasing the expression of HpARIh and inhibiting STAT6. Conclusion Early aerosolized inhalation budesonide can effectively inhibit the expression of inflammatory factors such as TNF-α, TGF-β and IL-13, and inhibit the expression of IL-13 by activating HpARIh/STAT signaling pathway, which can significantly reduce asthma.

R974

遼寧省教育廳計(jì)劃項(xiàng)目（201602223）；遼寧省科技廳攻關(guān)項(xiàng)目（2019-ZD-0652）