Effect Of Citric Acid Atomizaiton Inhalation On Toxicity Of Depleted Uranium Instillation In Rats’ Lung

Background Military and terrorist attacks, depleted uranium (DU) weapons, includingDU bombs and DU dirty bombs etc, has been widely used. Radioactive aerosol of DUproduced in DU ammunition explosion, may lead to long-term low levels ofradioactive pollution damage inside to the large crowds mainly by inhalation. Theinhaled of DU radioactive aerosol, especially the insoluble DU aerosol long-termretention in the lungs tissue and nearly lymph nodes, can cause serious damage to thelung tissue, including emphysema and pulmonary fibrosis and other respiratorydiseases, and even resulting lung cancer.Accelerate the rate of elimination, shorten residence time and concentration ofinsoluble DU aerosol deposited in interstitial lung, which is the most fundamentalmeasures to mitigate the DU aerosol inhalation caused damage to body. There is noeffective clinical treatment for pulmonary disease caused by insoluble DU aerosolsinhalation deposited, except whole lung lavage for the therapy at home and abroad. Inorder to reduce the damage of the inhalation of DU aerosol, it is necessary to researchand develop new drugs eliminating insoluble DU aerosol particles in lung.Objective To investigate the promoting effect of citric acid atomization inhalation onDU instillation dissolution and it,s involved mechanisms, and to further study on thetreatment for pulmonary disease caused by insoluble DU aerosol inhalation deposited.Methods Selecting Wister rats as subjects and the applying the way of orotracheal intubation giving suspension of insoluble DU particles, establish insoluble DUexposure animal model.30min after the exposure DU by orotracheal intubation, givenaerosol inhalation of20%(w v-1) citric acid, at a flow rate of1.44mL min-1,continuous administration once daily for7days, each for20min, observe thedissolution of DU and detoxification effect. The rats were randomly divided into salinecontrol group (control group), DU model group, citric acid inhalation group.respectively, after exposure7d,15d,30d killed rats, detection of the content of U inlung and kidney with wet digestion; count of whole blood cell, serum biochemistry,detection of serum biochemical indicator, thymic T cell subsets, observation of lungand kidney pathological changes by HE staining, collagen deposition in lung tissue byMasson staining, immunohistochemical analysis of matrix metalloproteinase-9(MMP-9) and woven metalloproteinase inhibitor-1(TIMP-1) expression in lungtissue.Results1) Compare with the control group, on day15day to30day, citric acidinhalation group and DU model group rats week weight gain was not inhibited, andeach group organ coefficient did not change significantly;2) Citric acid inhalationgroup and DU model group rats,7d,15d WBC tended to rise, but30d each groupWBC has been restored to normal level. RBC, HGB and PLT did not changesignificantly;3) Serum biochemical testing found that7d citric acid inhalation groupGOT, LDH, UA was significantly lower than DU model group. On day7d,15d and30d citric acid inhalation group CRE was lower than DU model group, but serummagnesium level is higher than DU model group;4)7d and15d, compared with DUmodel group, citric acid inhalation group rats peripheral blood of CD3+CD4+andCD3+CD4+/CD3+CD8+was significantly high, citric acid inhalation group and controlgroup no significant difference;30d the trend is not obvious, with the extension of exposure time, the DU model rats peripheral blood CD3~+CD4~+and CD3~+CD4~+/CD3~+CD8~+gradually increased, close to the ratio of control group;5) citric acid inhalationgroup lung uranium content is lower DU model group at the same time point, and withthe extension of exposure time, lung, kidney uranium content gradually decreased;6)fibroblast proliferation, bronchial epithelial cell loss, lymphocyte infiltration in citricacid inhalation group is lower than DU model group. Renal tubular epithelial celldegenerated;8) Masson staining observed that15d,30d citric acid inhalation groupcollagen deposition in lung is less than that in DU model group;8)Immunohistochemical analysis showed that DU model group lung interstitial MMP-9and TIMP-1increased gradually,15d and30d citric acid inhalation group weresignificantly reduced, compared with DU model group.Conclusion1) Establishment of inhalation of insoluble DU animal model wassuccessful, by the way of orotracheal intubation under the direction of the naked eyeperfusing DU particles suspension;2) Atomization inhalation of citric acid cansignificantly reduce acute lung injury caused by insoluble DU particles inhaled. It,smechanism may be is to improve pH microenvironment in lung, reduced DU content,the destruction of the alveolar wall, and inhibited fibroblast proliferation, regulate theamount of MMP-9and TIMP-1protein expression and extracellular matrix in adynamic equilibrium, to play a protective role.