Effect of Dachengqi decoction on NF-κB p65 expression in lung of rats with partial intestinal obstruction and the underlying mechanism

Abstract

To investigate the effect of Dachengqi decoction on NF-κB p65 expression in lung of rats with partial intestinal obstruction and the underlying mechanism, 30 SD rats were randomly divided into three groups: sham-operation group, model group and Dachengqi decoction treatment group (Dachengqi group), with 10 animals in each group. The models were made by partially ligating their large intestines outside the body. The pathological changes were analyzed by HE staining. The expression of NF-κB p65 in rats lung were measured by using real-time polymerase chain reaction and immunohistochemistry respectively. Moreover, the expression of caveolin-1 in rats lung was also measured to. Increased edema, interstitial thickening, hemorrhage, and infiltration of inflammatory cells were found in the model group. In contrast, this change was significantly reduced in Dachengqi group as compared with model group. In addition, the up-regulated caveolin-1 and NF-κB p65 were also suppressed by Dachengqi decoction in lung of rats with partial intestinal obstruction. We are led to concluded that the caveolin-1-NF-κB pathway plays an important role in the development of lung injury of rats with partial intestinal obstruction and Dachengqi decoction could down-regulate the expression of caveolin-1 and NF-κB p65 in lung of rats with partial intestinal obstruction.

Keywords

Dachengqi decoction / partial intestinal obstruction / lung injury / NF-κB p65 / caveolin-1

References

[1] SwankG.M., DeitchE.A.. Role of the gut in multiple organ failure: bacterial translocation and permeability changes. World J Surg, 1996, 20(4): 411-417

[2] SuliburkJ., HelmerK., MooreF., et al.. The gut in systemic inflammatory response syndrome and sepsis. Enzyme systems fighting multiple organ failure. Eur Surg Res, 2008, 40(2): 184-189

[3] MooreF.A.. The role of the gastrointestinal tract in postinjury multiple organ failure. Am J Surg, 1999, 178(6): 449-453

[4] YangS.L., LiD.B.. Clinical study on therapy of clearing hallow viscera in treating critical patients with gastro-enteric function disorder. Chin J Integr Med (Chinese), 2006, 12(2): 122-125

[5] LiD., YangS., ChenR.. Experimental study on the mechanism of protective effect of free fu on gut-derived endotoxin-mediated lung damage. J Huazhong Univ Sci Technol [Med Sci], 2004, 24(5): 528-530

[6] CowardW.R., OkayamaY., SagaraH., et al.NF-kappa B and TNF-alpha: a positive autocrine loop in human lung mast cells?, 2002, 169(9): 5287-5293

[7] LiQ., VermaI.M.. NF-kappaB regulation in the immune system. Nat Rev Immunol, 2002, 2(10): 725-734

[8] SenP., WalletM.A., YiZ., et al.. Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood, 2007, 109(2): 653-660

[9] KatoT.Jr, DelhaseM., HoffmannA., et al.. CK2 is a C-terminal IkappaB kinase responsible for NF-kappaB activation during the UV response. Mol Cell, 2003, 12(4): 829-839

[10] TergaonkarV., BotteroV., IkawaM., et al.. IkappaB kinase-independent IkappaBalpha degradation pathway: functional NF-kappaB activity and implications for cancer therapy. Mol Cell Biol, 2003, 23(22): 8070-8083

[11] BaldwinA.S.Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol, 1996, 14: 649-683

[12] SweeneyC., LiL., ShanmugamR., et al.. Nuclear factor-κB is constitutively activated in prostate cancer in vitro and is overexpressed in prostatic intraepithelial neoplasia and adenocarcinoma of the prostate. Clin Cancer Res, 2004, 10(16): 5501-5507

[13] BlackwellT.S., ChristmanJ.W.. The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol, 1997, 17(1): 3-9

[14] ChristmanJ.W., LancasterL.H., BlackwellT.S.. Nuclear factor kappa B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med, 1998, 24(11): 1131-1138

[15] SiebenlistU., FranzosoG., BrownK.. Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol, 1994, 10: 405-455

[16] EverhartM.B., HanW., SherrillT.P., et al.. Duration and intensity of NF-kappaB activity determine the severity of endotoxin-induced acute lung injury. J Immunol, 2006, 176(8): 4995-5005

[17] OhmoriK., TakedaS., MiyoshiS., et al.. Attenuation of lung injury in allograft rejection using NF-kappaB decoy transfection-novel strategy for use in lung transplantation. Eur J Cardiothorac Surg, 2005, 27(1): 23-27

[18] SadikotR.T., HanW., EverhartM.B., et al.. Selective I kappa B kinase expression in airway epithelium generates neutrophilic lung inflammation. J Immunol, 2003, 170(2): 1091-1098

[19] SkerrettS.J., LiggittH.D., HajjarA.M., et al.. Respiratory epithelial cells regulate lung inflammation in response to inhaled endotoxin. Am J Physiol Lung Cell Mol Physiol, 2004, 287(1): L143-L152

[20] AlcamoE., MizgerdJ.P., HorwitzB.H., et al.. Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-kappa B in leukocyte recruitment. J Immunol, 2001, 167(3): 1592-1600

[21] CklessK., van der VlietA., Janssen-HeiningerY.. Oxidative-nitrosative stress and post-translational protein modifications: implications to lung structure-function relations. Arginase modulates NF-kappaB activity via a nitric oxide-dependent mechanism. Am J Respir Cell Mol Biol, 2007, 36(6): 645-653

[22] JohnT.A., VogelS.M., TiruppathiC., et al.. Quantitative analysis of albumin uptake and transport in the rat microvessel endothelial monolayer. Am J Physiol Lung Cell Mol Physiol, 2003, 284(1): 187-196

[23] RazaniB., CombsT.P., WangX.B., et al.. Caveolin-1-deficient mice are lean, resistant to diet-induced obesity, and show hypertriglyceridemia with adipocyte abnormalities. J Biol Chem, 2002, 277(10): 8635-8647

[24] PelkmansL., PüntenerD., HeleniusA.. Local actin poly-merization and dynamin recruitment in SV40-induced internalization of caveolae. Science, 2002, 296(5567): 535-539

[25] CouetJ., SargiacomoM., LisantiM.P.. Interaction of a receptor tyrosine kinase, EGF-R, with caveolins. Caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem, 1997, 272(48): 30429-30438

[26] WilliamsT.M., HassanG.S., LiJ., et al.. Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: genetic ablation of Cav-1 delays advanced prostate tumor development in tramp mice. J Biol Chem, 2005, 280(26): 25134-25145

[27] GarreanS., GaoX.P., BrovkovychV., et al.. Caveolin-1 regulates NF-kappaB activation and lung inflammatory response to sepsis induced by lipopolysaccharide. J Immunol, 2006, 177(7): 4853-4860