目的 探究鹽酸氨溴索對(duì)毛細(xì)支氣管炎小鼠氣道高反應(yīng)性及白細(xì)胞介素17（IL-17）/信號(hào)傳導(dǎo)轉(zhuǎn)錄激活因子3（STAT3）通路的影響。方法 采用隨機(jī)數(shù)字表法將72只Balb/c小鼠隨機(jī)分為對(duì)照組、模型組、布地奈德組（20 mg/kg）、鹽酸氨溴索高、中、低劑量（60、30、15 mg/kg）組，每組12只。除對(duì)照組外，其余各組小鼠用呼吸道合胞病毒（RSV）混懸液滴鼻法復(fù)制毛細(xì)支氣管炎小鼠模型。造模完成后，給藥組小鼠霧化吸入相應(yīng)劑量的藥物，對(duì)照組和模型組小鼠霧化吸入生理鹽水，1次/d，連續(xù)7 d。雙腔體描計(jì)法檢測(cè)小鼠清醒狀態(tài)下的小鼠氣道阻力（sRaw）；檢測(cè)血清中IL-17、IL-6、IL-23水平；空斑法測(cè)定肺組織勻漿中病毒滴度；蘇木精-伊紅染色（HE）觀察肺組織病理變化；蛋白免疫印跡法（Western blotting）檢測(cè)肺組織中IL-17、p-STAT3、STAT3蛋白的表達(dá)。結(jié)果 與對(duì)照組相比，模型組小鼠sRaw，血清IL-17、IL-6、IL-23水平，肺組織勻漿病毒滴度，IL-17、p-STAT3/STAT3蛋白表達(dá)顯著升高（P<0.05），肺部支氣管及肺泡結(jié)構(gòu)明顯破壞，大量炎性細(xì)胞浸潤(rùn)，支氣管氣道變窄；與模型組相比，布地奈德組和鹽酸氨溴索高、中劑量組小鼠sRaw，血清IL-17、IL-6、IL-23水平，肺組織勻漿病毒滴度，IL-17、p-STAT3/STAT3蛋白表達(dá)明顯降低（P<0.05），肺組織炎癥明顯減輕。結(jié)論 鹽酸氨溴索可抑制炎性因子的表達(dá)，減輕毛細(xì)支氣管炎小鼠氣道炎癥反應(yīng)和氣道高反應(yīng)性；其作用機(jī)制可能與阻斷IL-17/STAT3途徑有關(guān)。

Objective To investigate the effects of ambroxol hydrochloride on airway hyperresponsiveness and interleukin-17 (IL-17)/signal transduction activator of transcription 3 (STAT3) pathway in mice with bronchiolitis.Methods Seventy-two Balb/c mice were randomly divided into control group, model group, budesonide group (20 mg/kg), high, medium and low dose ambroxol hydrochloride groups (60, 30, 15 mg/kg) according to the random number table, with twelve mice in each group. Except for the control group. The mice in other groups were made into bronchiolitis model by nasal drip of respiratory syncytial virus (RSV) suspension. After modeling, mice in the drug groups were given the corresponding dose of drugs, while mice in the control group and model group were inhaled with normal saline, once a day, for 7 d. The airway resistance (sRaw) in conscious mice was measured by dual chamber plethysmography. The levels of serum IL-17, IL-6, and IL-23 were detected. The virus titer in lung homogenate were measured by plaque method. The pathological changes of lung tissue were observed by HE staining, the expression of IL-17, p-STAT3, and STAT3 in lung tissue were detected by Western blotting. Results Compared with those in the control group, sRaw, levels of serum IL-17, IL-6 and IL-23, virus titer in lung homogenate, protein expression of IL-17 and p-STAT3/STAT3 of mice in model group were significantly higher (P<0.05), the structure of bronchus and alveoli of lung were destroyed, a large number of inflammatory cells infiltrated, and the bronchial airway became narrow. Compared with those in the model group, sRaw, the levels of serum IL-17, IL-6, and IL-23, virus titer in lung homogenate, protein expression of IL-17 and p-STAT3/STAT3 of mice in budesonide group, high and medium dose ambroxol hydrochloride groups were significantly lower (P<0.05), the inflammation of lung tissue was significantly reduced. Conclusion Ambroxol hydrochloride can inhibit the expression of inflammatory factors, reduce airway inflammation and airway hyperresponsiveness in mice with bronchiolitis, and its mechanism may be related to blocking IL-17/STAT3 pathway.

R965

河南省中醫(yī)藥科學(xué)專(zhuān)項(xiàng)項(xiàng)目（2019ZY2042）