Basic Research On The Injury Of Lungs About Paraquat Poisoning Rats And The Optimum Therapeutic Dose Of Ulinastatin

BackgroundParaquat is a kind of bigeminy pyridine herbicide. It has very strong toxicity for both human and domestic animals. However, it is not transparent about the mechanism of action for paraquat. There is no special effective antidote, so the mortality rate is very high. During early period, the poisoning persons often die form acute lung injury or ARDS; during advanced stage, they can die from respiratory failure caused by lung fibrosis. The researchers found that cytokine was one of the pathogenic mechanism for lung injury due to paraquat poisoning. TNF-a plays an especially important role. So, restraining the expression of TNF-a can do favor to postpone the lung fibrosis and reduce the mortality rate.ObjectiveThe main purpose is to investigate the pathogenic mechanism of paraquat and the optimum therapeutic dose of ulinastatin in treating paraquat poisoning.MethodsAt the beginning of the experiment, we made the poisoning rats model, then extracted the middle lobe of right lung on the 1st,3rd,7th,14th,21st, and 28th day respectively. With the methods of HE stain, Masson stain and immunohistochemical, we observe the pulmonary tissue and assay the content of TNF-a in lung tissue. All of the 140 rats are provided by experimental animal center of Jilin university. The body weight of the rats is (200±20) g, including male and female half-and-half. The rats are divided into seven groups randomly. Group A is the normal control group, using lml physiological saline intragastric administration. Group B is PQ poisoning group, using PQ solution 50mg/kg intragastric administration, and isodose physiological saline intraperitoneal injection. Group C is ulinastatin therapeutic group①, using ulinastatin thirty thousand iu/kg intraperitoneal injection and then twice a day. Group D is ulinastatin therapeutic group②, using ulinastatin sixty thousand iu/kg intraperitoneal injection and then twice a day. Group E is ulinastatin therapeutic group③, using ulinastatin ninty thousand iu/kg intraperitoneal injection and then twice a day. Group F is ulinastatin therapeutic group④, using ulinastatin one hundred and twenty thousand iu/kg intraperitoneal injection and then twice a day. Group G is ulinastatin therapeutic group⑤, using ulinastatin one hundred and eighty thousand iu/kg intraperitoneal injection and then twice a day. We extracted the lung tissue on the 1st,3rd,7th,14th,21st, and 28th day respectively after poisoning, then carried out the HE stain, Masson stain and immunohistochemical to observe the pulmonary tissue and assay the content of TNF-a in lung tissue, and then made statistic analysis to do group comparison. With the methods of HE stain, Masson stain, TNF-a immunohistochemical stain and measuring the grey level, we investigate the pathogenesis about the lung injury caused PQ and the therapeutic efficacy about different dose of ulinastatin.ResultsThe results of HE stain and Masson stain suggest that, the poisoning rats mainly show phlegmonosis on the early stage, and there are a lot of cytokine. Pulmonary fibrosis is the main manifestation during the latter period. Through the methods of TNF-a immunohistochemical stain and measuring the grey level and then statistic analysis, we find that the content of TNF-a raises immediately after poisoning.ConclusionUlinastatin injecta can obviously inhibit the inflammatory reaction of the lung tissue, the genesis of cytokine, the fibrosis of pulmonary and the expression of TNF-a in the PQ poisoning rats. This research verifies that during the therapeutic dose of ulinastatin, large dose has the best therapeutic efficacy.