The Regulating Action Of Hydrogen Sulfide On Oxidative Stress In Acute Lung Injury Induced By Agkistrodon Venom In Rats

Objective: To create a model of acute lung injury by injecting intraperitoneal Agkistrodonvenom in rats and study the increase or decrease H₂S content would affect the index ofantioxidation and oxidation, to explore the regulating action of H₂S on oxidative stress inacute lung injury rats induced by Agkistrodon Venom and the conceivable mechanisms.Methods:1. Grouping: Randomly, divided thirty-six male rats which were clean-level intosix groups, and there were six rats in each group. As follow:①Control group （Group N）;②Venom group（Group S）;③Venom and Low dose NaHS group（Group S+L）;④Venom and Middle dose NaHS group（Group S+M）;⑤Venom and High dose NaHSgroup（Group S+H）;⑥Venom and PPG group（Group S+PPG）.2. Method in detail:①Saline was injected into the abdominal cavity of Group N;Venom was respectively injected into the abdominal cavity of other groups.②3hourslater,Group N and Group S rats were injected intraperitoneally by saline;Group S+L,S+M, S+H rats were respectively injected intraperitoneally by Sodium hydrosulfide （NaHS）0.78mg/kg,1.56mg/kg and3.12mg/kg dose; Group S+PPG rats were administrated intoL-propargylglycine（PPG）.③6hours later, all of the rats were killed and the plasma andthe lung tissue were reserved.④Light microscopes were used to observe thehistopathological changes of HE-staining and a semi-quantitative histological index ofquantitative assessment （IQA） of lung injury was detected; the ratio of wet and dry weightof the lung tissue （W/D） were setting-out also. The contents of H₂S in plasma and theactivities of CSE in lung tissue were respectively assayed. The contents of8-Iso-Prostaglandin-F2α（8-iso-PGF2α）, and the activities of superoxide dismutase （SOD）and the activities of glutathione peroxidase （GSH-Px） in lung tissue were respectivelymeasured.Results:1. The changes of W/D: Compared with those of Group N, W/D increasedsignificantly in Group S （P＜0.01）. Compared with those of Group S, W/D did not varysignificantly in Group S+L （P＞0.05）, while both Group S+M and Group S+H decreased dramatically （P＜0.01）, and Group S+PPG increased significantly （P＜0.05）.2. The histopathological changes and IQA of lung injury: The normal structure ofpulmonary alveolar was damaged in S group versus the N group, such as the dilation of thecapillary in the interstitial of lung tissue, the thickened alveolar septum associated with theinterstitial edema, the increased capillary permeability, the infiltration of inflammatorycells and RBC into alveoli, and large tracts of pulmonary hyaline membrane either.Furthermore, the alveolar collapse and atelectasis also can be observed, and the grade ofIQA increased evidently （P＜0.01）. Compared with the Group S, the level of lung injurydid not alleviate significantly in Group S+L （P＞0.05）; while both the Group S+M and theGroup S+H, the level of lung injury was markedly relieved and the grade of IQAdecreased dramatically （P＜0.01）, and the level of lung injury of Group S+PPG wasmarkedly exacerbated and the grade of IQA increased dramatically （P＜0.05）.3. The contents of H₂S in plasma and the activities of CSE in lung tissue: Comparedwith Group N, contents of H₂S in plasma and the activities of CSE in lung tissuedescended markedly in Group S （P＜0.01）. Compared with Group S, the contents of H₂Sin plasma and the activities of CSE in lung tissue changes was no statistical mean in GroupS+L （P＞0.05）, but the two measure index above ascended significantly in the GroupS+M and the Group S+H （P＜0.01）, and descended in the Group S+PPG （P＜0.01or P＜0.05）.4. The activities of SOD and GSH-Px in lung tissue: Compared with Group N,activities of SOD and GSH-Px in lung tissue were significantly descended in Group S （P＜0.01）. Compared with Group S, the activities of SOD and GSH-Px in lung tissue changeswas no statistical mean in Group S+L （P＞0.05）, but the two index above ascendedsignificantly in the Group S+M and the Group S+H （P＜0.01）, and descended in the GroupS+PPG （P＜0.01or P＜0.05）.5. The contents of8-iso-PGF2α in lung tissue: Compared with Group N, contents of8-iso-PGF2α in lung tissue ascended significantly in Group S （P＜0.01）. Compared with Sgroup, Compared with Group S, the contents of8-iso-PGF2α in lung tissue changes was nostatistical mean in Group S+L （P＞0.05）, but in the Group S+M and the Group S+Hdescended dramatically （P＜0.01）, and ascended dramatically in the Group S+PPG （P＜0.01）.Conclusion:1.By way of exogenous increase the contents of H₂S can ascend the activities of SOD and GSH-Px in lung tissue and descend the contents of8-iso-PGF2α,can alleviatethe lung injury induced by Agkistrodon Venom; while restrain the produce of H₂S candescend the activities of SOD and GSH-Px in lung tissue and ascend the contents of8-iso-PGF2α, aggravate the lung injury.2. H₂S relieve the hyperoxidation in acute lung injury （ALI） in rat induced byAgkistrodon Venom maybe across to improve the imbalance of oxidant/antioxidant status.