Protective Effect Of Dexamethasone On Rats With Hydrochloric Acid-induced Acute Lung Injury

Background and ObjectiveAspiration of gastric contents into the lung is a fatal complication in clinical anesthesia, but there has not been an effective strategy to treat it yet. Therefore, prevention and cure of reflu and aspiration has always been a major research subject in the field of clinical anesthesia. The previous studies on the amimal models established by aspirating acid(HCl), the main ingradients of gastric juice, revealed that the later phase induced by HC1 pathologically resemble acute distress syndrome(ARDS). The occurrence of ARDS is due to the unbalance of cytokines network, in which proinflammatory express excessively, thus activating a great number of polymorphonuclear neutrophils (PMN). It is these PMNs that aggregate in the inflammatory sites, release leactive oxygen species (ROS) and protease which result in lung tissue injury ultimately. With the clinical evaluation and empirical study, clinicians started to realize the therapeutic action of glucocorticoid on acute lung injuy, but phammacodynamic action therapeutic opportunity and dosage, course of treatment were disputed in internal country and overseas. In this article the author considered the therapeutic regimen in the earlier period, with middle or small dose, long- time and gradual decrement was acceptable. The purpuse of this experiment is to study the method of reproduce the model of acute lung injury (ALI) in rats through hydrochloric acid (HCL) intratracheal injection, study the protective effect and mechanism of small dosage dexamethasone on rats with hydrochloric acid-induced ALI.Materials and MethodsModel establishment and grouping: hydrochloric acid was used to reproduce the model of ALI in rats. Seventy two adult SD rats were randomly divided into four groups and there were eighteen rats in every group: control group(A group); injured group(B group); the first treated group(C group); the second treated group(D group), In the injured group, after their tracheas had been cut open, the rats were instillaed intraracheally with HCL(PH=1.25, 1.2ml/kg); the rats in C group andreceived intraperitoneal Dex(2mg/kg) immediately after being administered with HCL in the same way as group B; D group was given Dex(2mg/kg) through intraperitoneal injection 30min after being administered with HCL; In the control group, the same amount of normal saline was injected into the trachea, without applying any treatment. Every group has eighteen animals, the animals were killed at 1h, 2h, 6h and the samples were collected. Serum and bronchoalveolar lavage fluid(BALF) were prepared to determine the total cells count, protein concentration and the level of tumor necrosis factor alpha(TNF-α) and Interleukin-8(IL-8) in bronchoalveolar lavage fluid(BALF). The W/D ratio of the right middle lobe of lung is measured. The right bellow lobe of lung was used to histopathologic study. The data were expressed as mean±SD. Statistical package (SPSS 10.0) was used for processing data.αas 0.05 was considered to be statistical significant.Results(1) Light microscope examination:Pathological changes of lung tissue: Light microscopic findings including extensive morphologic lung damage; hemorrhage, edema, infiltration of inflammatory cells, proteinaceous, exudates of Group C and D were less severe than those of Group B. No remarkable damages were found in Group A.(2) Electron microscope observation: Lung capillary basement membranes of group A were comparatively complete, type II penumonocytes were round or ellipse, had plentiful endochylema, microvilli and laminated bodies were comparatively complete, the continuities of group B were abscised, the cells of capillary endothelium were swelling, endothelial cells' intercellular space were widen, type II penumonocyte microvilli were seriously destroyed and became fewer, even disappeared. Type II penumonocyte laminated body was empty. The microstructure of group C and D was only lightly destroyed, degree of injury was between group A and group C.(3) W/D: In the groups of B,C and D, W/D were higher than it of the control group(p<0.05), Comparing to injured group and the second treated group, W/D in the first treated group decreased(p<0.05).(4) Total leukocytes and the protein concentration in the BALF: in the group of B,C and D, the leukocytes and the protein concentration in the BALF were higher than those of the control group(p<0.05); Comparing to injured group, the protein concentration in the BALF in the first treated group decreased (p<0.05), but not in the second treated group.(5) The concentrations of TNF-αin serum and BALF: Comparing to control group, both the concentrations of TNF-αin serum and in BALF in other three group increased (p<0.05); Comparing to injured group, the concentrations of TNF-αin serum and BALF decreased in the first treated group(p<0.05). The first treated group and the second treated group had similar concentration of TNF-αin serum.(6) The concentrations of IL-8 and IL-10 in BALF: In BALF of the other three groups, the concentrations of IL-8 and IL-10 were higher than those of the control (p<0.05), comparing to injured group, the concentrations of IL-8 in BALF decreased in the first treated group (p<0.05) and the concentrations of IL-10 in BALF increased in the first treated group (p<0.05). The first treated group and the second treated group had similar concentration of IL-10 in BALF.Conclusions(1) The method of reproducing the model of ALI in rats through hydrochloric acid (HCL) intratracheal injection is good. (2) TNF-α,IL-8,IL-10 may play important role in the inflammatory process of hydrochloric acid-induced acute lung injury in rats vivo in our experiment., small dosage Dexamethasone may relieve lung injuries by intervene discharging of TNF-α,IL-8,IL-10.(3) There are be possible relation at the progress of inflammation with the intervene time of Dexamethasone, the effect of Dexamethasone is good if given early.