Effects of large dose of ambroxol hydrochloride on lung ischemia reperfusion injury in rats
10.3760/cma.j.issn.1001-8050.2009.12.355
- VernacularTitle:大剂量氨溴索对大鼠肺缺血再灌注损伤的影响
- Author:
Peng ZHANG
;
Peng ZHANG
;
Yuan CHEN
- Publication Type:Journal Article
- Keywords:
Reperfusion injury;
Transplantation;
Vascular endothelial growth factor;
Hypoxia inducible factor 1 alpha;
Ambroxol hydrochloride
- From:
Chinese Journal of Trauma
2009;25(12):1116-1122
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the protective effect of large dose of ambroxol hydrochloride on lung ischemia reperfusion injury in rats and analyze the relationship between ambroxol hydrochloride and pulmonary vascular permeability mediators including EphrinAl, HIF-1α and VEGF at mRNA and protein levels.Methods Rats were operated by the thoracic posterolateral approach.The left lung is-chemia was induced by clamping the hilum of the left inflated lung for 60 minutes, and then followed by a 6-hour reperfusion.Forty rats were divided into ischemia-reperfusion group, ambroxol hydrochloride inter-vention group, sham operation group and blank control group.At the beginning of reperfusion, rats in am-broxol hydrochloride group were infused with ambroxol hydrochloride solution (3.75 mg ·kg~(-1) ·h~(-1)) via femoral vein for six hours.Then, PaO_2, wet-to-dry lung weight ratio, concentrations of IL-1β and TNF-a, activity of myeloperoxidase (MPO), mRNA and protein expressions of EphrinAl, HIF-1a and VECF were detected.Histopathological changes were observed under light microscope.Results (1) Histo-logical observation with light microscope showed significant decrease of diffuse alveolar damage consisting of septal edema, intraalveolar hemorrhage and exsudation in ambroxol hydrochloride group compared with ischemia-reperfusion group.The wet-to-dry lung weight ratio in ambroxol hydrochloride group was de-creased and PaO_2 was elevated significantly.(2) Compared with ischemia-reperfusion group, the concen-trations of IL-1β and TNF-α and activity of MPO in ambroxol hydrochloride group were decreased signifi-cantly.(3) The mRNA and protein expressions of EphrinAl, HIF-la and VEGF in ambroxol hydrochl-oride group did not recover to normal but were down-regulated significantly compared with ischemia-reper-fusion group.Conclusions (1) Large dose of ambroxol hydrochloride can alleviate the LJRI damage by down-regulating the expressions of IL-1β and TNF-α and the activity of MPO in the lung parenchyma.(2) The mRNA and protein expressions of EphrinA1, HIF-1α and VECF can be down-regulated by large dose of ambroxol hydrochloride, which contributes to alleviation of the LJRI damage.The results indicate possible role of gene regulation and fresh pharmacological effect of ambroxol hydrochloride during forma-tion of LIRI.
