氨溴索对盐酸吸入性肺损伤保护作用的实验研究

Study on the Protection of Ambroxol Hydrochloride to Injury of Lungs from Aspiration of Hydrochloric Acid

目的观察预先使用盐酸氨溴索(沐舒坦)对盐酸吸入性肺损伤是否具有保护作用,并探讨其可能机制。方法将24只大鼠随机等分为3组:生理盐水吸入组(A 组);稀盐酸吸入组(B 组);稀盐酸吸入+沐舒坦处理组(C 组)。C 组予以50mg/kg 沐舒坦腹腔注射,1次/d,连续3 d,A、B 组则以等容积生理盐水腹腔注射代替。第3天腹腔注射沐舒坦或生理盐水30 min后,A 组以1.2 mg/kg 生理盐水经气管注入制作假盐酸吸入肺损伤作模型为对照;B,C 组则用 HCl+生理盐水配制成 pH 值为1.25的混合液以1.2 mg/kg 气管注入制成盐酸吸入肺损伤模型。观察盐酸注入5 h 后大鼠动脉血气,肺组织匀浆和血清中 TNFα、IL-8的含量。结果盐酸吸入后5 h PaO_2明显下降,而沐舒坦预先处理后能抑制 PaO_2的下降程度,3组间比较均有显著性差异(P<0.01)。盐酸吸入5 h 后肺组织匀浆中 TNFα和 IL-8值的影响,3组间两两比较差异均有显著性(P<0.05和 P<0.01)。盐酸吸入后可引起血中 IL-8明显升高,而沐舒坦能抑制 IL-8升高,3组间比较差异有显著性(P<0.01)。盐酸吸入可引起 TNFα轻度上升,但3组间比较差异无显著性(P>0.05)。结论稀盐酸吸入可造成血氧分压下降,盐酸氨溴索可能通过抑制 TNFα、IL-8炎症因子的产生和释放机制来改善氧合,对盐酸吸入性肺损伤有保护作用。

Objective To observe the protection of ambroxol hydrochloride to injury of lungs from aspiration of hydrochloric acid and approach its possible mechanism. Methods 24 rats were divided into three groups. （A）group;Isotonic Na chloride group. （B） group diluted hydrochloric acid. （C） group：Dilute hydrochloric acid group and ambroxol hydrochloride group. Group C were peritoneal injected ambroxol hydrochloride 50 mg/kg,qd for 3 days. While groups A and B were peritoneal injection of isotonic Na chloride. On the third day , group were infused 1.2 mg/kg of isotonic Na chloride through the trached as the pseudo-hydrochloric acid to form pulmonary injury which used as control ,while group B and C were infused the same amount mixture of isotonic Na chloride and hydrochloric acid （pH 1.25 ） by aspiration to compare to its pulmonary injury. 5 hours later, observed the rats＇ ABG and TNFα, IL-8 content in the homogenate lung tissue and the serum. Results PaO2 was evidently decline. Group C could inhibit the declination . There were significant difference amount the three groups （ P 〈0.01 ）. The content of TNFα and IL-8 in lung tissue were different affected evidently by infusion hydrochloric acid （ P 〈 0. 05 or P 〈0. 01 ）. Hydrochloric acid could cause the content of IL-8 raise in serum, but ambroxol hydrochloride could inhibit the affection, there were significant difference among the three groups （ P 〈0.01 ） ,hydrochloric acid could slightly raise TNFα, but there were no significant difference among the three groups （ P 〈 0.01 ）. Conclusion Oxygen partial pressure could decrease by infusion of Hydrochloric acid. Ambroxol hydrochlofide improved oxygenation by inhibition releasing of TNFα and IL-8 inflammatory factor , it could protect the injury of lungs for infusion hydrochloric acid.