| 1Objective1.1To determine the effect of androgen depletion on the pathology changeof lung tissue in male rats with OA-induced ALI/ARDS;1.2To determine the effect of androgen depletion on the ratio of wet/day oflung tissue in male rats with OA-induced ALI/ARDS;1.3To determine the the effect of androgen depletion on the expression ofalveolar ENaC-ａmRNA and protein in male rats with OA-inducedALI/ARDS;1.4To determine the effect of androgen on the degree of lung injury inmale rats with OA-induced ALI/ARDS by the way of gonad castration;2Method20healthy male SD rats(180-220g) provided by the experimentalanimal center of Chongqing Medical University were randomly dividedinto four group(n=5) according to the random digits table with5rats ineach group, they were normal control group,OA model group,castratedmodel group and sham-castrated model group according to the random digits table with5rats in each group. The model was copied by injection ofOA (0.15ml/kg) through tail vein, and the castrated model group andsham-castrated model group were castrated2weeks before exposure to OA.After6h exposure to OA, The behavior、color of skin-mucous membraneand respiratory rate of all rats were observed to judge whether the ALImodel was successful or not after6-hour injection of OA. Then the chestwas opened to retrieve lung issues after all rats were fully anesthetized by3.5%chloral hydrate(10ml/kg), the hemorrhage and edema of lung tissueswere observed after thoracotomy,the upper right lung tissues were excisedfor measurement of lung wet/dry weight(W/D)ratio,the middle right lungtissues were used to histopathology analysis; the lower right lung tissueswere packed to store at-80℃refrigerator for use to detect the level ofENaC-ａmRNA in lung tissue by PCR, the left lung tissues were used todetermine the expression of ENaC-ａprotein by Western blot.3Result3.1The behavior, color of skin-mucous membrane and respiratory rate ofall ratsThe rats in control group,their normal condition and mental state werewell, breath steadily and respiratory rate was (84.50±3.749), their lips andskin were pink with no cyanosis, no death. In a short period of time aftermodeling, rats in OA model group, castrated model group andsham-castrated model group showed that respiratory rate significantly increased(OA model group:119.10±7.172; castrated model group:106.70±8.920; sham-castrate model group:118.20±5.808),body hairserected, activities reduced and cyanosis of lips was more obvious comparedwith control group, but the condition in castrated model group wassignificantly attenuated compared with OA model group such as therespiratory rate was reduced from119.10±7.172to106.70±8.920, andthere is no significant difference between OA model group andsham-castrated model group (p>0.05).3.2The pathology change of lung tissueLung tissue of rats in control group was pink, with no significantcongestion, bleeding and swelling in naked eyes. The structure of the lungtissue including the alveolar wall was intact and clear under lightmicro-scope, there were hardly inflammatory cells infiltration in thealveolar interstitium and no edema fluid in cavity. In OA model group, thelung tissue was dark red and swollen signifcantly, with visible bleeding andcongestion. A large area of the alveolar wall was destructed with thealveolar cavity filled with pink edema fluid, alveolar septum widened andedema. Inflammatory cells infiltration, leakage of red blood cells as wellas pulmonary vascular congestion were also seen in this group. The samepathological changes observed in OA model group could be seen incastrated model group, but the damaged area was significantly reduced,with less alveolar space edema fluid, alveolar interstitial edema, inflammatory cells infiltration and red blood cells leakage. Lung tissue ofrats in sham-castrated model group was similar to that of OA model groupboth by naked eyes and light microscopy.3.3The effect of androgen depletion on the ratio of wet to dryW/D ratio in OA model group were significantly increased comparedwith normal group （model group vs. control group,P=0.000;sham-castrated model group vs. control group, P=0.000;castratedgroup vs. control group，P=0.000）, W/D ratio in castrated model groupwere significantly attenuated compared with OA model group（P=0.000）,there is no significant difference between OA model groupand sham-castrated model group(P=0.183).3.4The effect of androgen depletion on expression of ENaC-ａmRNAthe expression of mRNA of ENaC-ａin OA model group weresignificantly lower than that of normal group（model group vs. controlgroup, P=0.000; sham-castrated model group vs. control group, P=0.000;castrated group vs. control group，P=0.001）, the expression of mRNA ofENaC-ａin castrated model group were significantly up-regulated than OAmodel group（castrated group vs. model group, P=0.002）, there is nosignificant difference between OA model group and sham-castrated modelgroup（P=0.940）.3.5The effect of androgen depletion on expression of ENaC-ａproteinthe expression of protein of ENaC-ａin OA model group were significantly lower than that of normal group（model group vs. controlgroup, P=0.000; sham-castrated model group vs. control group, P=0.000;castrated group vs. control group，P=0.045）, the expression of protein ofENaC-ａin castrated model group were significantly up-regulated than OAmodel group（castrated group vs. model group, P=0.030）, there is nosignificant difference between OA model group and sham-castrated modelgroup（P=0.834）.4conclusion1) Androgen depletion by the way of castration of both gonad can alleviatethe degree of lung injury and decrease the accumulation of fluid intoalveolar after injection of OA;2) Androgen depletion by the way of castration of both gonad canup-regulate the expression of ENaC-ａmRNA;3) Androgen depletion by the way of castration of both gonad canup-regulate the expression of ENaC-ａprotein;4) Androgen may aggravate the degree of lung injury,increase the fluidand imflammatory cell sequestered into alveolar, and restrain theexpression of ENaC-ａmRNA and protein. |
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