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Pesticides are the people security, the promotion the important agricultural means of production, the growth of plants and crops essential paraquat (paraquat, PQ) is a non-selective contact herbicide organic heterocyclic, because of their herbicidal performance, low pollution rapidly inactivated, contact with soil, residue, etc. are widely used in the world. PQ to humans and animals have strong toxicity, showed an increasing trend with the the PQ widely used in the world of PQ poisoning events, especially in rural areas, most farmers due to oral suicide. Since there was no magic antidote, PQ poisoning mortality as high as 80%. PQ can enter the body through the respiratory tract, in contact with skin and gastrointestinal absorption of a variety of ways, and with the blood distributed to body tissues and organs, causing organ damage, especially in acute lung injury (Acute lung injury, ALI) and pulmonary fibrosis, is the leading cause of death by poisoning PQ poisoning mechanism is not yet entirely clear. PQ has a strong affinity for lung tissue, lung is the main target organ for PQ injury, type I and type II alveolar epithelial cells PQ selective cytotoxicity of target cells. PQ in the lung tissue, an unusually large number of aggregation, PQ, and a diamine, a polyamine having the structural similarity exists polyethylene amines pickup system because the lungs, PQ by alveolar type Ⅱ cells with amines competition energy dependence of the polyamine uptake pathways selectively gathered in the lung, and low concentrations of PQ throughput energy dependence of the polyamine uptake system gathered in the lung tissue, but in the high concentration of PQ role in the case of the system deactivation, primarily through diffusion pathway into the cell. Early in the PQ poisoning, mainly for acute alveolar inflammation, pulmonary edema, congestion and other symptoms of ALI, and then induced acute respiratory distress syndrome (the Acute Respiratory distresssyndrome ARDS), and eventually died of respiratory failure, even in the early stages of poisoning survived, the number of weeks later, there will still be an irreversible pulmonary fibrosis, leads to death. Therefore, to clarify the mechanism of PQ-induced ALI, looking for a PQ blockers or looking to be able to promote the PQ as soon as possible as soon as possible metabolic toxic substances, is the key to effective treatment and prevention of PQ poisoning. In recent years, some studies suggest that PQ poisoning caused by ALI mainly related to excessive production of reactive oxygen species (Reactive oxygen species, ROS). PQ after entering the body through a series of oxidation reduction reaction can rapidly produce a large amount of ROS excess ROS attack lung tissue, causing oxidative damage of the lung. Metallothionein (Metallothionein, MT) is a class of low molecular weight present in vivo, a mercapto group-rich, the metal is induced by the metal binding protein. MT has a variety of biological effects, its anti-oxidation, free radical scavenging capabilities of particular concern. Therefore, the subject of choice of MT gene knockout animals by observing the MT-I / II genotype sensitivity of the knockout (MT-/ -) mice and with the corresponding wild-type (MT /) mice PQ poisoning difference-depth study of the body at the molecular level, an important endogenous protective protein MT PQ-induced ALI any protective effect explore MT PQ-induced ALI and possible mechanisms, looking for to be able to effectively antagonize the toxic effects of PQ endogenous material to provide a theoretical and experimental basis. In this study, application of cadmium - hemoglobin saturation assay C57BL/OLA129 MT-Ⅰ / Ⅱ gene knockout (MT-/ -) mice and their homologous wild-type (MT /) mouse lung tissue content of MT, the results show MT / MT of mouse lung tissue content of approximately MT-/ - mice three times, and thereby verify the reliability of the experimental model. 24 hours after the PQ, MT / mice lung tissue was significantly higher than MT MT-/ - mice. MT / 'mice and MT-/ - mice given 24 hours after the PQ treatment, there are loss of appetite, food intake and water intake significantly reduced, weight loss, slow performance, shortness of breath. PQ-treated MT / mice with untreated MT / mice compared lung wet weight / body weight ratio was no significant difference (P gt; 0.05), and MT-/ - mice were given PQ treatment of lung wet weight / body weight ratio increased significantly, significantly higher than the untreated MT / mice (P lt; 0.05) PQ before MT / mice, and the WBC number close to the MT-/ - mice blood. 24 hours after the PQ, mice blood WBC number was significantly higher (P lt; 0.05) between the two mice, the number of WBC was no significant difference (P gt; 0.05) PQ poisoning can change the structure of the lung tissue, the study showed that 24 hours after the PQ Both mouse alveolar wall thickening, capillary dilatation and congestion, inflammatory cell infiltration in the lung tissue, severe pulmonary hemorrhage, alveolar spaces disappear , which were filled with a large number of inflammatory cells and exudate; the MT / mouse and MT-/ mice mice compared visible MT-/ - mice lung lesions compared with the MT / mouse serious. Malondialdehyde (MDA) is one of the end products of lipid peroxidation products, and its content reflects the tissue cells of the degree of lipid peroxidation, thiobarbituric acid (TBA) chromogenic method for the determination of the content of MDA. The results showed that exposure, MT / mice and MT-/ - mouse lung tissue MDA content close; the PQ exposed mice lung tissue MDA content were significantly increased, and MT-/ - mice lung lipid peroxidation was significantly higher than MT / mouse. MT PQ induced lung tissue antioxidant defense system from the damage of a protective effect, compared with the MT / mice, MT-/ - mice after the PQ, the lung tissue of non-enzymes antioxidants GSH content and antioxidant enzymes SOD, CAT, GSH-Px and GR activities were significantly lower. These results indicate that the mechanism of PQ induced ALI with free radicals and oxidative damage, MT has a significant protective effect on the PQ-induced lung tissue toxicity. Apoptosis of lung tissue caused by the ALI another mechanism, PQ In recent years, studies have shown that free radical-mediated apoptosis in lung tissue may play a key role in the PQ-induced lung tissue lesions. Mitochondrial damage and dysfunction of the early signs of PQ induced apoptosis in lung tissue. In this study, TUNEL immunohistochemical assay of apoptosis in lung tissue, and the application of Western blotting method for determination of Bax, Bcl-2 and Caspase-3 protein expression. The results show that the PQ-induced lung tissue of mice severe apoptosis, compared with the MT / mice, MT-/ - mice after the PQ, the lung tissue apoptotic index was significantly increased, Bax, Bcl-2, Cleaved-caspase-3 protein expression and Bax/Bcl-2 value of significantly increased. It is suggested that MT can inhibit the PQ-induced apoptosis in lung tissue. MT can inhibit the expression of Bax, reduce the ratio of Bax/Bcl-2 of cells known as \Consolidated results of this study, PQ can lead to acute injury of the lungs of mice, the PQ cause acute lung injury in mice with free radicals and oxidative damage. The PQ also be induced severe apoptosis in mouse lung tissue. MT can reduce the PQ-induced acute lung injury in mice extent and apoptosis in lung tissue specific antagonistic mechanism MT radical scavenging and antioxidant related.
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