| Objective: It is to observe the effects of the increase or decrease the generation ofH2S on inflammatory factor, the nuclear factor (the NF-kappa B) and Intercellularadhesion molecule (ICAM-1) in acute lung injury of rats induced by AgkistrodonJiang Zhe Venom and to explore the possible mechanism.Methods: Methods:1. Grouping: Clean-level rats，thirty-six males，wererandomly divided into six groups(n=6): Control group; S, Agkistrodon Jiang ZheVenom group(1.5mg/kg);S+ls, Agkistrodon Jiang Zhe Venom and Low dose NaHSgroup(0.78mg/kg);S+ms, Agkistrodon Jiang Zhe Venom and Middle dose NaHSgroup(1.56mg/kg); S+hs, Agkistrodon Jiang Zhe Venom and High dose NaHSgroup(3.12mg/kg);S+PPG, Agkistrodon Jiang Zhe Venom and PPG group(30mg/kg).2. Methods in detail: Saline was administrated into Control group with intrapertionealinjection according to the dose above, and Agkistrodon Jiang Zhe venom into theother groups. Three hours later Sodium hydrosulfide(NaHS) of low, middle, highdose, and DL-propargylglycine (PPG) were respectively administrated into S+ls、S+ms、S+hs and S+PPG group.After anther three hours, all rats were killed and theplasma and the lung tissue the experiment needs is obtained. The contents ofinterleukin-1β (IL-1β) and interleukin-10(IL-10) in serum is detected in ELISAmethod; the expression of intercellular adhesion molecule-1(ICAM-1), IL-1β, IL-10mRNA in lung tissue were measured with RT-PCR method; and expression of proteinof NF-κB in lung tissue detected by western-blot method.Results:1.The histopathologic changes by light microscopes and IQA of lunginjury:①Compared with Control group, thenormal structure of pulmonary alveolarwas destroyed in Agkistrodon Jiang Zhe Venom group, along with pulmonaryinterstitial blood capillary dilation, hyperemia, interstitial oedema, and the alveolar septum thickenness, the infiltration of inflammatory cells within alveoli, increasedmicrovascular permeability and red blood cell leakage with lysis. Sometimes thealveolar collapse, even the hyaline membrane and atelectasis can also be found, andthe grade of IQA increased Significantly (P＜0.01).②C ompared with that ofAgkistrodon Jiang Zhe Venom group, the degree oflung injury was alleviated unsignificantly in Agkistrodon Jiang Zhe Venom+lsgroup(P＞0.05); in Agkistrodon Jiang Zhe Venom+ms group and Agkistrodon JiangZhe Venom+hs one, the lung injury was markedly ameliorated and the grade of IQAdecreased dramatically(P＜0.01),③w hile the lung injury ofAgkistrodon Jiang Zhe Venom+PPG group wasmarkedly aggragated compared with those of other groups and the grade of IQAincreased significantly(P＜0.05). The extensive hyaline membrane and atelectasiswere showed in Agkistrodon Jiang Zhe Venom+PPG group.2. The change of IL-1β and IL–10contents in Serum①Compared with control group, the contents of IL-1β and IL-10in serum weresignificantly increased in Agkistrodon Jiang Zhe Venom group（P＜0.01）.②Compared with Agkistrodon Jiang Zhe Venom group, the content of IL-1β inserum was significantly deceased in Agkistrodon Jiang Zhe Venom+NaHS Middleand High dose groups，but slightly deceased in Agkistrodon Jiang Zhe Venom+NaHSLow dose groups and had no statistical significance.（P＞0.05）.③Compared with Agkistrodon Jiang Zhe Venom group, the content of IL-10inserum was significantly increased in Agkistrodon Jiang Zhe Venom+NaHS Middleand High dose groups（P＜0.05或P＜0.01）,but slightly increased in AgkistrodonJiang Zhe Venom+NaHS Low dose groups and had no statistical significance.（P＞0.05）.④Compared with Agkistrodon Jiang Zhe Venom group, the content of IL-1β inserum was significantly increased and the content of IL-10in serum was significantlydecreased in Agkistrodon Jiang Zhe Venom+PPG group（P＜0.05或P＜0.01）.3. The changes of the expression of IL-1β, IL-10and ICAM-1mRNA in lungtissue. ①Compared with control group, the expression of IL-1β, IL-10and ICAM-1mRNA in lung tissue were significantly increased in Agkistrodon Jiang Zhe Venomgroup（P＜0.01）.②Compared with Agkistrodon Jiang Zhe Venom group, the expression of IL-1βand ICAM-1mRNA in lung tissue were significantly decreased in A AgkistrodonJiang Zhe Venom+NaHS Low, Middle and High dose groups (P＜0.05or P＜0.01).③Compared with Agkistrodon Jiang Zhe Venom group,the expression of IL-10mRNA in lung tissue were significantly increased in Agkistrodon Jiang Zhe Venom+NaHS Middle and High dose groups (P＜0.05or P＜0.01), but slightlyincreased in Agkistrodon Jiang Zhe Venom+NaHS Low dose groups and had nostatistical significance.（P＞0.05）.④Compared with Agkistrodon Jiang Zhe Venom group, the expression of IL-1βand ICAM-1mRNA in lung tissue were significantly increased（P＜0.05），while theexpression of IL-10mRNA was significantly decreased in the Agkistrodon Jiang ZheVenom+PPG group (P＜0.05).4. The change of the protein expression of NF-κBp65①Compared with control group, the expression of protein of NF-κBp65in lungtissue were significantly increased in Agkistrodon Jiang Zhe Venom group（P＜0.01）.②Compared with Agkistrodon Jiang Zhe Venom group, the expression of proteinof NF-κBp65in lung tissue were significantly decreased in Agkistrodon Jiang ZheVenom+NaHS High dose groups (P＜0.05),but slightly decreased in AgkistrodonJiang Zhe Venom+NaHS Middle and Low dose groups and had no statisticalsignificance.（P＞0.05）.③Compared with Agkistrodon Jiang Zhe Venom group, the expression of proteinof NF-κBp65in lung tissue were significantly increased in the Agkistrodon Jiang ZheVenom+PPG group (P＜0.05).Conclusion:1. By the exogenous increasement of the content of H2S in rats which had been exposed to the Agkistrodon Venom,the expression of the IL-1β,ICAM-1gene and the NF-κBp65protein had been decreased.And the expression of the IL-10gene had been elevated while the IQA of the lung tissue had been decreased.2. The degree of the lung injury induced by Agkistrodon Venom could be reduced byhydrogen sulphide through inhibited the release of pro-inflammatory cytokinesand increase the concentration of anti-inflammatory cytokines simultaneously. |
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