尼可地尔对慢性阻塞性肺疾病模型大鼠气道炎症的影响

Effects of Nicorandil on the Airway Inflammation of Rats with Chronic Obstructive Pulmonary Disease

目的观察钾通道开放剂尼可地尔对慢性阻塞性肺疾病(COPD)模型大鼠支气管肺泡灌洗液中白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)水平和气道炎症细胞表面黏附分子CD11b表达的影响。方法18只Wistar大鼠分为3组:对照组、模型组和治疗组,每组6只。以气道内滴注脂多糖(LPS)和熏烟法建立COPD模型,治疗组从第2天起每天熏烟前以尼可地尔3 mg.kg-1灌胃,对照组同时予0.9%氯化钠溶液。4周后收集支气管肺泡灌洗液(BALF),对炎症细胞行总数和分类记数,对大鼠肺脏行病理学检查,并采用免疫组化法检测炎症细胞表面CD11b的表达,以酶联免疫吸附法(ELISA)检测BALF中IL-6、TNF-α的表达水平。结果模型组BALF中IL-6、TNF-α及CD11b的表达明显高于对照组(P<0.05),而治疗组的表达较模型组明显降低(P<0.05)。结论IL-6、TNF-α和CD11b在COPD大鼠气道的表达明显增多,尼可地尔能抑制COPD模型大鼠气道炎症细胞表面CD11b的表达和BALF中IL-6、TNF-α的表达,从而对COPD的气道炎症起到一定的防治作用。

Objective To evaluate the protective and therapeutic effects of potassium channel opener , nicorandil （NCR）, on the expression of interleukin-6 （IL-6）, tumor necrosis factor-α （TNF-α） in the bronchoalveolar lavage fluid （ BALF）, and the adhesion molecule CD11 b on the inflammation cells in BALF of rats with chronic obstructive pulmonary disease （COPD）. Methods Eighteen Wistar rats were equally divided into 3 groups,the control, model , and treatment groups. The models of COPD were established by intratrachel instillation of lipopolysaccharide （LPS） and daily exposure to cigarette smog. From the second day the rats in treatment group received intragastric administration of NCR with a dose of 3 mg·kg^-1 before smog exposure. The control group was established by intratrachel instillation of normal saline without cigarette smog exposure. After four weeks, total and differential cell counts in bronchoalveolar lavage fluid （BALF） were observed, and the pathomorphological changes in the lung were analyzed. The expresssion of CD11b on the surface of inflammatory cells were detect by immunohistochemistry. The expressions of IL-6 and TNF- α in the BALF were evaluated by ELISA. Results Compared with the control group, the expressions of IL-6, TNF-α and CD11 b was significantly higher in model group（ P 〈 0. 05 ）, and the expressions of those in treatment group were significantly lower than those in the model group（ P 〈 0. 05 ）. Conclusion The expressions of IL-6,TNF-α and CD11b are significantly higher in the COPD group than those in the control group. Nicorandil presents preventive and therapeutic effects on the airway inflammation of COPD by decreasing the expression of CD11 b on inflammation cells and IL-6, TNF-α in the BALF.