Effects Of Penehyclidine Hydrochloride On Acute Lung Injury Following Trauma/Hemorrhagic Shock And Resuscitation In Rats

Objective: This study is designed to investigate the effects of Penehyclidine hydrochloride on acute inflammatory injuries, degeneration of I-κB protein and translocation of NF-κB from cytoplasm to nucleus, as well as the expression of TNF-αin lung tissues in rats following trauma/hemorrhagic shock(THS) and resuscitation.Methods: 32 adult male SD rats were randomly assigned into three groups: Sham group, Resus1 group (THS and resuscitated with shed blood and Lactic Ringer's solution in 2 times of shed blood in volume) and Resus2 group (THS and resuscitation the same as Resus1 group and combined with the treatment of Penehyclidine hydrochloride). The rat model of THS and resuscitation was established according to the description of Chaudry IH. Rats in sham group were just cathetered to left femoral vein and carotid, and blood presure was monitored, but no trauma and hemorrhagic shock and resuscitation. The treatment with penehyclidine hydrochloride in dosage of 1mg/kg was combined in Resus2 group. 24 hours postprocedure, all rats were killed and the lung tissues were harvested for measuring lung wet-dry weight ratio and observing morphological changes under light microscope. The expression of TNF-αwith immunohistochemistry staining, the content of I-κB in cytoplasm with western-blotting, and NF-κB p65 in nucleus with immunohistochemistry staining and western-blotting were performed.Results: 24 hours after THS and resuscitation, inflammatory injuries could be detected in lungs in Resus1 group and Resus2 group. The most notable change observed was an increase in number of imflammatory cells. There were also an increase in interstitial thickening, alveolar disruption and alveolar edema seen more frequently in Resus1 group and Resus2 group comerpared with sham group, lung wet-dry weight ratios were also significantly higher than that in Sham group(P<0.01), the content of I-κB protein in cytoplasm decreased, and NF-κB protein in nucleus as well as TNF-αin lung increased obviously(P<0.01). However, compared with that in Resus1 group , the inflammatory injuries were significantly slighte(rP<0.05), and wet-dry weight ratios obviously lower in Resus2 group. Correspondingly, the changes of I-κB protein and TNF-αin cytoplasm, and NF-κB in nucleus in Resus2 group were more slighter too.Conclusions: The experiment has been performed indicated that trauma/hemorrhagic shock and resuscitatiocn indued lung inflammatory injuries, degeneration of I-κB protein in cytoplasm, translocation of NF-κB to nucleus, as well as an increase of proinflammatory cytokine TNF-αexpression in lung. The treatment with Penehyclidine hydrochloride in the early stage of resuscitation for trauma/hemorrhagic shock reduced the inflammatory injuries, and the mechanism of this effect may be on its inhibiting the degeneration of I-κB and preventing the activation and translocation of NF-κB to nucleus, and then inhibitting the increase of TNF-αexpression in lung following trauma/hemorrhagic shock and resuscitation. This result suggested that the using of Penehyclidine hydrochloride may get a beneficial effect to treat trauma/hemorrhagic shock and resuscitation.