辛伐他汀对大鼠气道黏液高分泌的影响和机制研究

Effect of simvastatin on airway mucus hypersecretion in rats and its molecular mechanism

目的了解辛伐他汀对丙烯醛引起的气道黏液高分泌的作用及其可能的机制。方法大鼠雾化吸入丙烯醛,建立气道黏液高分泌模型。将42只雄性SD大鼠按随机数字表法分为7组:对照组(A组)、辛伐他汀自身对照组(B组)、模型组(C组)、低剂量辛伐他汀组(D组)、中剂量辛伐他汀组(E组)、高剂量辛伐他汀组(F组)和甲羟戊酸组(G组),每组6只。分别用阿辛蓝-过碘酸雪夫(AB-PAS)和免疫组化染色检测气道黏蛋白和黏蛋白5ac(mucin5ac,MUC5ac)的表达。RT-PCR检测MUC5ac mRNA的表达。结果丙烯醛刺激可以使大鼠气道黏蛋白、MUC5ac蛋白和mRNA表达增高,使支气管肺泡灌洗液中巨噬细胞数增多。结论辛伐他汀可以抑制丙烯醛所致的气道黏液高分泌,甲羟戊酸可以部分逆转辛伐他汀的作用,其机制可能是通过甲羟戊酸途径减少巨噬细胞在肺中的浸润。

Objective To explore the effect of simvastatin on airway mucus hypersecretion in rats. Methods Rat airway mucus hypersecretion was induced by acrolein. Forty-two male SD rats were randomly divided into 7 groups, with 6 rats in each group. The rats in groups D, E, F were intragastfically administered simvastatin （5, 10, 20 mg/kg respectively） 1 d before spray atomization of acrolein once a day for 12 d and those in group G were simultaneously given 20 mg/kg simvastatin and 20 mg/kg mevalonate intraperitoneally. The rats in groups A and B received no spray atomization of acrolein, and those in group B were given 20 mg/kg simvastatin intragastically once a day, which both served as control. Mucin and mucinSac were detected with Alcian blue-periodic acid sthiff and immunohistochemistry, and mucinSac mRNA by RT-PCR. Results Acrolein significantly induced the expression of mucinSac mRNA and protein in bronchial epithelium, and increased the concentration of mucin and macrophage number in BALF. Simvastatin significantly suppressed bronchial mucinSac expression and reduced the number of macrophages and the concentration of mucin. The effect of simvastatin can be partly reversed by mevalonate. Conclusion Simvastatin inhibits airway mucus hypersecretion induced by acrolein, which might be related to the reduction of macrophage infiltration through mevalonic acid pathway.