| Objective: Paraquat (PQ) is the world's most widely used herbicide currently. In recent years, with the growing application of PQ in China, poisoning was reported on rising trend. Although PQ is very effective in weeding, its toxicity to human and animal is much high. Currently its pathogenesis has not been completely clarified , and there is not much effective treatment measures, not to mention magic antidote. In our clinical observation, we found that the poisoning patients of larger dose often died from the heart, liver, kidney, lung and other organs failure, while the poisoning survival of smaller dose often have delayed pulmonary fibrosis, who have a relatively longer duration. Access to literature, at present there is no more comprehensive exploration of experiments between different doses of an important PQ poisoning and organ damage. So we designed a system test from the pathological changes in enzymatic targets, biochemical blood tests and other aspects of the PQ poisoning caused vital organs damage characteristics in order to seek more effective targeted therapeutic drugs.Methods : In this study we do research through the establishment of animal models. Firstly with sterile saline we configured solution concentration 5mg/ml by using 20% of the PQ. Selection adult male mice 112, weight 25±5 g were randomly divided into four groups (n = 28) : ①normal control group (intraperitoneal injection of saline 75mg/kg),②Paraquat injection of low-dose group (intraperitoneal injection of paraquat 50mg/kg),③Paraquat injection of medium-dose group (intraperitoneal injection of paraquat 75mg/kg)④Paraquat injection of high-dose group (intraperitoneal injection of paraquat 100mg/kg). The animals were tested after poisoned by 6h, 1d, 3d, 7d,14d,28d,which were observed mortality and bays for blood tests respectively, including liver function (ALT, AST) , renal function (BUN, Cr). Then we killed animals each every four respectively. Then we autopsied those mice, dislodged their right lung and some liver tissue, which were quick-frozen in liquid nitrogen and then placed in -85℃so as to detect the archaeus of superoxide dismutase(SOD) and content of malondialdehyde (MDA) in homogenate by using kit. We dyed hepatic tissue, renal tissue and left lung tissue in HE method and investigated the histopathologic changes. Lungs of low dose group, in addition to routine HE staining, were dyed bigem for collagen and elastic fiber. All test results were analyzed with the control group respectively, and did analysis of variance of the variety.Results : 1. Low-dose exposure group after poisoned appeared anorexia, slightly weight reduced, shortness of breath and the other performance, but restored around 7 days. Mice in medium and high-dose group were significantly injured to respiratory system, nervous system, digestive system, and weight loss. Most of the mice died during 3-7 days. 2. From histopathological observation, we found that in low-dose exposure group mice liver and kidney damage were more slightly than those in medium and high-dose exposure group, and high-dose exposure group in early stage appeared liver cell necrosis and large protein tubular pipe type while low-dose exposure group mainly showed pulmonary fibrosis later, high-dose exposure group can be seen early pulmonary hemorrhage, the mice of which mostly died from multiple organ failure in early stage. 3. SOD and MDA in liver tissue homogenate of low-dose exposure group was no significantly differenct(P> 0.05) , and the changes of medium and high-dose exposure group ,at most points of the time, were significant (P <0. 05 or 0.01). And at the same time, the higher the exposure dose, the more obvious changes. 4. Serum ALT, AST, BUN, Cr values of low-dose exposure group increase significantly later (P <0. 05). Early in the 3d BUN increased (P <0. 05), and at the other time points did not change significantly (P> 0. 05). All values were increased significantly (P<0.05或P<0.01) except for aminotransferase in the medium dose exposure group at the 6 hours time point. High-dose exposure group at all the time points mouse serum ALT, AST, BUN, Cr were significantly increased (P<0. 05或P<0. 01).Conclusion: According to the experimental results, we considered that: 1. In low dose exposure group, liver and kidney tissues pathological damage was slight, and circulatory obstacles was the main aspect and accompanied with light engorge of cell, its performance of small arteriovenous and capillary congestion, slow-flow blood and cytosis of dicaryocyte in liver tissue and engorge of nephric tubule cellula epithelialis. In addition to lung tissue congestion, the main change showed up pulmonary fibrosis in late stage, mainly in late stage lung fibrosis and local fibrosis tendencies. In medium and large-dose exposure group there were liver cell hydropic degeneration, point necrosis, pulmonary hemorrhage, edema , and protein and epithelium were more visible within the renal tubular in early stage. 2. SOD and MDA in liver tissue homogenate of low-dose exposure group was no significantly different, which showed up its less oxidative damage, and SOD decreased and MDA increased significantly in lung tissue, and lipid peroxidation seriously injuried. SOD and MDA in liver and lung tissue of medium and large-dose exposure group changed significantly, and lipid peroxidation seriously injuried. 3. In low dose exposure group, serum ALT and AST values did not change significantly at the beginning, but increased later, and BUN value of the third day after exposure significantly increased, Cr in 28 days have increased, which showed that in low exposure dose group liver disease accompanied with dysfunction of pulmonary and reduction of blood oxygen concentration and injured significantly in late stage; kidney as a major PQ metabolic organ remained a certain damage after poisoned in low dose. serum ALT, AST, BUN, Cr of medium and high-dose exposure group increased significantly, that is, liver and kidney both seriously injuried.
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