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目的研究在大鼠气管内滴入MARCKS相关多肽(MANS)或/和地尔硫(DTZ)对气道黏蛋白5AC(MUC5AC)分泌的影响并探讨其可能的作用机制。方法通过雾化吸入丙烯醛建立大鼠气道黏液高分泌模型后随机分为4组,对照组气管内滴入生理盐水,三个实验组即MANS组、DTZ组和联用组在气管内分别滴入MANS、DTZ以及二者同时滴入,1 h后获取支气管肺泡灌洗液(BALF)及肺组织。用ELISA法对BALF中的MUC5AC进行定量;用免疫组化染色对气道杯状细胞中MUC5AC进行特异性染色,用灰度扫描和图像分析对杯状细胞内的MUC5AC进行半定量分析。结果BALF中MUC5AC的分泌量在MANS组和联用组均较对照组明显减少(P均<0.05),在DTZ组无明显变化(P>0.05);在联用组较MANS组亦明显减少(P<0.05)。气道杯状细胞内MUC5AC的量在MANS组和联用组均较对照组显著增多(P均<0.05);在单用DTZ组没有明显变化(P>0.05)。结论在丙烯醛诱导的大鼠气道黏液高分泌模型中,气管内滴入MANS可以减少气道黏液的分泌,单用DTZ气管内滴入不能减少气道黏液的分泌。但二者联合滴入时DTZ对MANS抑制气道黏液的分泌可能具有协同作用。
Objective To investigate the effect of intranasal administration of MARCKS-related polypeptide (MANS) and / or diltiazem (DTZ) on the secretion of airway mucin 5AC (MUC5AC) in rat trachea and to explore its possible mechanism. Methods The rat model of airway mucus hypersecretion was established by inhalation of acrolein. The rats were randomly divided into 4 groups. The control group was infused with normal saline into the trachea. The three experimental groups, MANS group, DTZ group and combined group, Instillation of MANS, DTZ, and simultaneous infusion of both, 1 h after bronchoalveolar lavage fluid (BALF) and lung tissue. MUC5AC in BALF was quantified by ELISA. MUC5AC in airway goblet cells was stained immunohistochemically. MUC5AC in goblet cells was semi-quantitatively analyzed by grayscale scanning and image analysis. Results The secretion of MUC5AC in BALF was significantly decreased in both MANS group and combined group (P <0.05), but not in DTZ group (P> 0.05), but also significantly lower in combined group than in MANS group P <0.05). The amount of MUC5AC in goblet cells was significantly increased in MANS group and combined group as compared with control group (all P <0.05), but not in DTZ group (P> 0.05). Conclusions In the acrolein-induced rat model of airway mucus hypersecretion, intratracheal instillation of MANS can reduce airway mucus secretion, and tracheal instillation with DTZ alone can not reduce airway mucus secretion. However, the combination of DTZ and MANS may inhibit the secretion of mucus in the airway.