Experimental Study On The Therapeutic Effect Of High Dose Ambroxol Against Acute Lung Injury Caused By Paraquat Poisoning

0bjectiveParaquat poisoning in the early phase can cause acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Patients usually die of multi-organ function failure or respiratory failure. The undermining pathogenesis is unclear. There is no ideal therapy at present. Modern research assume that lipid peroxidation impairment induced by hyper production of free radical may play an important role in the pathogenesis of ALI/ARDS caused by paraquat poisoning. Anti-oxidation and oxygen free radicals clearance drugs have been little effect when used in clinic. Previous study showed that ALI/ARDS patients had abnormal pulmonary surfactant(PS)system. PS inducer therapy could ease ALI/ARDS and retain pulmonary function. But little is reported in ALI/ARDS caused by paraquat. Ambroxol is a multibioactivity mucolytic agents. A great deal of studies showed that high dose ambroxol has effection on facilitating pulmonary surfactant synthesis, anti-oxidative injuries, cleaning free radical and anti-inflammation. We observed high dose ambroxol affecting on redox cycling and pulmonary surfactant-associated protein A(SP-A) through animal acute lung injury model caused by peritoneally paraquat injection and evaluate therapeutic effect of high dose ambroxol in the early phase of paraquat poisoning.Materials and Methods 1 Preparations One hundred and thirty-six healthy male Sprague-Dawley rats , weighting 240-350gm , were divided into three groups randomly and each of the three groups were separately divided into four subgroups randomly according to four different intervals(1, 3, 5 and 7 days ). (1) NS group (n=24) :the same volume of 0.9% saline solution was injected into peritoneal cavity every day. (2) PQ group(n=56): 2% paraquat (25mg/kg) was injected into peritoneal cavity at the first day. (3) AT group(n=56): ambroxol (35mg/kg) was injected into peritoneum daily after praraquat intoxication . There were twenty-four rats in NS group and each of subgroups has six rats. Each of 1d, 3d, 5d subgroups in PQ group and AT group had twelve rats and there were twenty rats in 7d subgroups respectively. Fatality rate was observed in 7d subgroups.2 Measurements Venous blood was obtained from heart under anesthesia. Isolated left lung tissue and collected right bronchoalveolar lavage fluid (BALF) .Protein content in BALF was measured . The number of WBC ,the percentage of PMN , the content of MDA and GSH-Px , SOD activity in blood and BALF were routinely measured . Left lung tissue were observed through both light microscope (LM) and electron microscope (TEM). The expression of SP-A was observed under multimedia color pathological image pattern after immunohistochemical SP staining .3 Statistical MethodsAnalysis was performed for statistical analysis with aid of SPSS11.5 software .All data were expressed as mean+standard error of the mean. Differences among groups were tested by one-way analysis of variance (ANOVA) followed by a least significant difference (LSD) test when significant differences were detected .P values less than 0.05 were considered statistically significant. Results 1 The fatality rate of group 7days There were no dead in NS group. Fifteen rats were dead in PQ group (fatality rate 75%). Eight rats were dead in AT group (fatality rate 40%) .There is significant difference between PQ group and group AT. (x2=5.01,P<0.05) 2 Protein contents in BALF There was no significant difference among NS group(P＞0.05). Protein content was increased after the administration of praraquat. PQ group or AT group comparied with NS group at the same time had significant difference(P<0.01) . Protein contents was obviously lower in AT group then that in PQ group at the same time(P<0.01).3 The results of blood and BALF 3.1 The quantity of WBC in blood .There was no significant difference among NS group .The quantity of WBC was increased after the administration of praraquat. PQ group or AT group comparied with NS group at the same time had signi...