The Effect Of Hydrogen Sulfide On PGE₂in Acute Lung Injury Rat Induced By Agkistrodon Halys Pallas Venom

Objective: To study the effect of hydrogen sulfide （H₂S） and cystathionine-γ-lyase （CSE）,on PGE₂in acute lung injury rat induced by Agkistrodon Halys Pallas Venom and itspossible mechanism on inflammation.Methods:Rats, clean-level, thirty-six male, were randomly divided into six group（n=6）, such asN: Control group, S: Venom group（1.5mg/kg）, S+NaHS L: Venom and NaHS Lowdose（0.78mg/kg） group, S+NaHS M: Venom and NaHS Middle（1.56mg/kg） dose group,S+NaHS H: Venom and NaHS High dose （3.12mg/kg） group, and S+PPG: Venom andPPG（30mg/kg） group. Saline or Vemon were respectively administrated into Contol groupor others with intraperitoneal injection according to the dose above. Sodium hydrosulfide（NaHS） low, middle and high dose, or L-propargylglycine（PPG） were respectivelyadministrated into S+NaHS L, S+NaHS M, S+NaHS H or S+PPG group after three hours.At six hours after administration of saline or vemon, all rats were killed and obtain theplasma and the lung tissue the experiment need. The ratio of wet and dry weight of thelung tissue（W/D）, the histopathologic changes of HE-staining by light microscopes and asemi-quantitative histological index of quantitative assessment （IQA） of lung injury wererespectively detected. The content of H₂S and PGE₂in plasma, the activity of CSE and theexpression of mPGES-1mRNA in lung tissue were respectivly assayed.Results:1. The degree of acute lung injury （the histopathologic changes by light microscopesand changes of W/D）: Compared with N group, the intact structure of pulmonary alveolarwas damaged in S group, along with pulmonary interstitial blood capillary dilation,hyperemia, interstitial oedema, and the alveolar septum thickenness, the infiltration ofinflammatory cells within alveoli, increased microvascular permeability and RBC leakagewith lysis. Sometimes the alveolar collapse, even the hyaline membrane and atelectasis canalso be found, and the grade of IQA and W/D increased dramatically（P＜0.01or P＜0.05）.Compared with that of S group, two measure indices above were alleviated unsignificantlyin S+NaHS L group（P=0.193＞0.05or P=0.233＞0.05）); in S+NaHS M group andS+NaHS H one, the grade of IQA and W/D decreased dramatically（P＜0.01） and the lung injury were markedly ameliorated, while the grade of IQA and W/D increasedsignificantly（P＜0.05） was markedly aggragated compared with those of other groups andthe lung injury of S+PPG group. The extensive hyaline membrane and atelectasis wereshowed in S+PPG group.2. The level of H₂S in plasma and the activity of CSE in lung tissue: The level of H₂Sin plasma and the activity of CSE in lung tissue were significantly descended in othergroups compared with those of N group （P＜0.01or P＜0.05）. Compared with S group,the level of H₂S in plasma and the activity of CSE in lung tissue were unsignificantlychanged in S+NaHS L group （P＝0.079＞0.05or P＝0.634＞0.05）, and two measureindices above were ascended dramatically in S+NaHS M and S+NaHS H groups （P＜0.05或P＜0.01）, while were descended in S+PPG group （P＜0.01or P＜0.05）.3. The expression of mPGES-1mRNA in lung tissue: Compared with that of N group,the level of mPGES-1mRNA gene expression in S group and others was dramaticallyincreased（P＜0.01or P＜0.05）. Compared with S group, the level of mPGES-1mRNAgene expression was unchanged sinificantly in S+NaHS L group（P＝0.161＞0.05）, anddecreased dramatically in S+NaHS M and S+NaHS H group（P＜0.01）, which still higherthan that of N group. The level of mPGES-1mRNA gene expression in S+PPG group wasincreased severely compared with S group（P＜0.01）.4. The content of PGE₂in plasma:Compared with those of N group, the content ofPGE₂in plasma increased dramatically in S group and others （P＜0.01）. The contents ofPGE₂in plasma, were decreased significantly（P＜0.05or P＜0.01） in S+NaHS L,S+NaHS M, and S+NaHS H group, while was increased severely in S+PPG group（P＜0.01） compared with those of S group.5. Correlation analysis: In S+NaHS L, S+NaHS M, and S+NaHS H group, there weremediate negatively correlation between the content of H₂S in plasma and IQA of lunginjury（r＝-0.700, P＜0.01）, mediate positively correlation between the concentration ofPGE₂in plasma and IQA of lung injury（r＝0.781, P＜0.01）, mediate negatively correlationbetween the content of H₂S and the concentration of PGE₂in plasma（r＝-0.790, P＜0.01）.Conclusions:1. The upregulation of the system of Hydrogen sulfide （H₂S） andcystathionine-γ-lyase can alleviate acute lung injury （ALI） in rat induced by AgkistrodonHalys Pallas Venom. 2. H₂S involving in the possible mechanism on antiflammatory response of ALI wasrelated to the decreasement of PGE₂via the downregulation of mPGES-1mRNA.