The Mechanism Of Lung Injury Induced By Intestinal Ischemia-reperfusion In Rats And The Protective Effects Of Veratrum Nigrum Alkaloids

Background: The obstacle of intestinal ischemia-reperfusion (IIR) isnot necessarily limited to the intestine itself,but involved in the distanttissue severe destruction because of reperfused oxygenated blood.Manyreporters indicated that IIR is an important event in the pathogenesis ofMODS,which is the leading cause of death in critically ill patients.It hasincreasingly evident that lung dysfunction is responsible for the majority oftissue injury in IIR. It has been reported that nuclear factor kappa B(NF-κB)is actived during the acute lung injury. But, there have been no studies onthe relation of NF-κB and lung injury induced by IIR till now. Veratrum nigrum alkaloids(VnA) is a blocker of inactive gate ofsodium channel, which has potent capacity of modulating cellmetabolization and gene expression and which probably has protectiveeffects on lung injury induced by intestine ischemia - reperfusion. Purpose: This article is designed to examine the mechanism of lunginjury induced by intestinal ischemia reperfusion in rats and to investigatethe preconditioning protective effects of veratrum nigrum alkaloids , inorder to provide preclinical pharmacological basis for its new clinical uses. Methods: Rats were randomly divided into 3 groups: sham group,model group, and VnA preconditioning group. The IIR model wasestablished by clamping superior mesenteric artery (SMA)for 1 hour andreperfusing for 2 hours. VnA was administered (20ug/kg body weight,IP) at30 minutes before ischemia. In the sham group, SMA was only isolatedwithout clamping. Blood sample, intestine and lung tissue samples werecollected after reperfusion 2 hours, as assessed by 1) protein concentrationof bronchia alveolus lung fluid [BALF] and NF-κBp65 expression inlung,intestine and lung histology pathology. 2)lung oxidation injury(superoxide dismutase[SOD] activity, malondialdehyde [MDA] in thetissue of lung); 3)cytokines: tumor necrosis factor-α [TNF-α] in serum;4)neutrophil accumulation: (myeloperoxidase [MPO activity,intercellularadhesion molecule [ICAM-1] expression in the tissues of lung) Result: Compared with sham group, activities of SOD was decreased,MPO was increased, the level of MDA , expression of ICAM-1 ,NF-κBp65 in lung and TNF-α in serum was increased . At the same time,protein concentration of BALF was increased. Intestine and lung weredestroyed obviously on gross pathology. Compared with model group, VnApreconditioning can increase SOD activity, decrease MDA content,MPOactivity and ICAM-1,NF-κBp65 expression in lung,TNF-α in serum andprotein content in BALF were decreased. And, VnA could attenuateintestine and lung tissue injury. Conclusion: 1)This study demonstrated that intestinal I/R may result insincerely lung damage, the mechanism may be involved of oxidation injury ,activated polymorphonuclear nutrophils (PMN) accumulation and cytokinesmediators.2)The mechanism of lung injury induced by IIR is complicatedwhich has relation on the activation of NF-κB.3)VnA can protect lung againstIIR injury, which may be associated with ameliorating oxidation injury ,decreasing the aggregation and activation of PMN and the release of cytokinesmediators,which may be related with inhibiting the activition of NF-κB.