Influence of Intestinal Lymphatic Ligation on Pulmonary Injury in Rats with Severe Acute Pancreatitis

Abstract

Objective

The present study explored the mechanisms involved in intestinal lymphatic ligation in rats with severe acute pancreatitis (SAP).

Methods

Male Sprague Dawley rats were randomly divided into 4 groups: saline group, saline+ligation group, SAP group, and SAP+ligation group. Rats in the SAP group were administered sodium taurocholate solution. Isolated mesenteric lymph duct ligation was administered to the saline+ligation and SAP+ligation groups. Endotoxin (ET), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), myeloperoxidase (MPO), and superoxide dismutase (SOD) were detected. Nuclear factor-κB (NF-κB) and intercellular cell adhesion molecule-1 (ICAM-1) proteins were observed. The mRNA of inducible nitric oxide synthase(iNOS) and Toll-like receptor 4 (TLR4) was detected by PCR.

Results

Pathomorphological analysis showed that necrosis was present in the lung of rats in the SAP group, but only mild lesions in the SAP+ligation group. ET, NO, TNF-α, and IL-1 in the serum and lung tissue were significantly decreased and MPO was increased in the SAP+ligation group as compared with the SAP group. However, MPO was increased. The expression of NF-κB and ICAM-1, either iNOS or TLR4, was upregulated in the SAP group, but downregulated in the SAP+ligation group. Intestinal lymph duct ligation prevented ET translocation, the release of inflammation factors, and inflammation injury.

Conclusion

The intestinal lymph duct ligation could alleviate SAP-induced pulmonary injury by suppressing NF-κB activation in rats.

Keywords

intestinal lymphatic ligation / severe acute pancreatitis / lung injury / intestinal bacterial translocation

References

[1] FeiS, LiW, XiangL, et al.. Protective Effect of Alprostadil on Acute Pancreatitis in Rats via Inhibiting Janus Kinase 2 (JAK2)/STAT3 Signal Transduction Pathway. Med Sci Monit, 2019, 25: 7694-7701

[2] SpanierB, BrunoMJ, DijkgraafMG. Incidence and mortality of acute and chronic pancreatitis in the Netherlands: a nationwide record-linked cohort study for the years 1995–2005. World J Gastroenterol, 2013, 19(20): 3018-3026

[3] FishmanJE, LevyG, AlliV, et al.. The intestinal mucus layer is a critical component of the gut barrier that is damaged during acute pancreatitis. Shock, 2014, 42(3): 264-270

[4] ShenQ, LiZ, HuangS, et al.. Intestinal mucosal barrier dysfunction in SAP patients with MODS ameliorated by continuous blood purification. Int J Artif Organs, 2018, 41(1): 43-51

[5] SuS, LiangT, ZhouX, et al.. Qingyi decoction attenuates severe acute pancreatitis in rats via inhibition of inflammation and protection of the intestinal barrier. J Int Med Res, 2019, 47(5): 2215-2227

[6] CreasyC, SchanderA, OrlowskiA, et al.. Thoracic and abdominal lymphatic pump techniques inhibit the growth of S. pneumoniae bacteria in the lungs of rats. Lymphat Res Biol, 2013, 11(3): 183-186

[7] ButerA, ImrieCW, CarterCR, et al.. Dynamic nature of early organ dysfunction determines outcome in acute pancreatitis. Br J Surg, 2002, 89(3): 298-302

[8] SharpeSM, QinX, LuQ, et al.. Loss of the intestinal mucus layer in the normal rat causes gut injury but not toxic mesenteric lymph nor lung injury. Shock, 2010, 34(5): 475-481

[9] HouC, ZhuX, ShiC, et al.. Iguratimod (T-614) attenuates severe acute pancreatitis by inhibiting the NLRP3 inflammasome and NF-kappaB pathway. Biomed Pharmacother, 2019, 119: 109455

[10] SambolJT, LeeMA, CaputoFJ, et al.. Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction. J Appl Physiol (1985), 2009, 106(1): 57-65

[11] ShanbhagST, ChoongB, PetrovM, et al.. Acute pancreatitis conditioned mesenteric lymph causes cardiac dysfunction in rats independent of hypotension. Surgery, 2018, 163(5): 1097-1105

[12] LaiF, ZhangY, XieDP, et al.. A Systematic Review of Rhubarb (a Traditional Chinese Medicine) Used for the Treatment of Experimental Sepsis. Evid Based Complement Alternat Med, 2015, 2015: 131283

[13] YuJH, KimH. Oxidative stress and inflammatory signaling in cerulein pancreatitis. World J Gastroenterol, 2014, 20(46): 17324-17329

[14] AhoHJ, SuonpaaK, AholaRA, et al.. Experimental pancreatitis in the rat. Ductal factors in sodium taurocholate-induced acute pancreatitis. Exp Pathol, 1984, 25(2): 73-79

[15] PeridesG, van AckerGJ, LaukkarinenJM, et al.. Experimental acute biliary pancreatitis induced by retrograde infusion of bile acids into the mouse pancreatic duct. Nat Protoc, 2010, 5(2): 335-341

[16] DeitchEA, AdamsC, LuQ, et al.. A time course study of the protective effect of mesenteric lymph duct ligation on hemorrhagic shock-induced pulmonary injury and the toxic effects of lymph from shocked rats on endothelial cell monolayer permeability. Surgery, 2001, 129(1): 39-47

[17] GuoY, WangL, MaR, et al.. JiangTang XiaoKe granule attenuates cathepsin K expression and improves IGF-1 expression in the bone of high fat diet induced KK-Ay diabetic mice. Life Sci, 2016, 148: 24-30

[18] MunirF, JamshedMB, ShahidN, et al.. Advances in immunomodulatory therapy for severe acute pancreatitis. Immunol Lett, 2020, 217: 72-76

[19] FlintRS, PhillipsAR, PowerSE, et al.. Acute pancreatitis severity is exacerbated by intestinal ischemia-reperfusion conditioned mesenteric lymph. Surgery, 2008, 143(3): 404-413

[20] PandeyS, SrivastavaSK, RamanaKV. A potential therapeutic role for aldose reductase inhibitors in the treatment of endotoxin-related inflammatory diseases. Expert Opin Investig Drugs, 2012, 21(3): 329-339

[21] Romo-VaqueroM, Cortes-MartinA, Loria-KohenV, et al.. Deciphering the Human Gut Microbiome of Urolithin Metabotypes: Association with Enterotypes and Potential Cardiometabolic Health Implications. Mol Nutr Food Res, 2019, 63(4): e1800958

[22] WangY, LiuW, LiuX, et al.. Role of liver in modulating the release of inflammatory cytokines involved in lung and multiple organ dysfunction in severe acute pancreatitis. Cell Biochem Biophys, 2015, 71(2): 765-776

[23] RagyMM, AliFF, ToniN. Comparing the preventive effect of sodium hydrosulfide, leptin, and curcumin against L-arginine induced acute pancreatitis in rats: role of corticosterone and inducible nitric oxide synthase. Endocr Regul, 2019, 53(4): 221-230

[24] KantrongN, ToTT, DarveauRP. Gingival Epithelial Cell Recognition of Lipopolysaccharide. Adv Exp Med Biol, 2019, 1197: 55-67

[25] AiresRS, VieiraLD, FreitasA, et al.. NO mediates the effect of the synthetic natriuretic peptide NPCdc on kidney and aorta in nephrectomised rats. Eur J Pharmacol, 2019172780

[26] FisicE, PoropatG, Bilic-ZulleL, et al.. The Role of IL-6, 8, and 10, sTNFr, CRP, and Pancreatic Elastase in the Prediction of Systemic Complications in Patients with Acute Pancreatitis. Gastroenterol Res Pract, 2013, 2013: 282645

[27] SimsekO, KocaelA, KocaelP, et al.. Inflammatory mediators in the diagnosis and treatment of acute pancreatitis: pentraxin-3, procalcitonin and myeloperoxidase. Arch Med Sci, 2018, 14(2): 288-296

[28] XuXW, YangXM, JinZX, et al.. Effect of Ginkgo biloba extract on the function of alveolar polymorphonuclear neutrophils in severe acute pancreatitis rats complicated with lung injury. Zhongguo Zhong Xi Yi Jie He Za Zhi, 2014, 34(4): 460-465

[29] HuangL, JiangY, SunZ, et al.. Autophagy Strengthens Intestinal Mucosal Barrier by Attenuating Oxidative Stress in Severe Acute Pancreatitis. Dig Dis Sci, 2018, 63(4): 910-919

[30] LiA, HuWM, LuHM, et al.. Study of the function and mechanism of interleukin cytokines in acute pancreatitis rats. Sichuan Da Xue Xue Bao Yi Xue Ban, 2011, 42(3): 358-363

[31] ParkAM, KudoM, HagiwaraS, et al.. p38MAPK suppresses chronic pancreatitis by regulating HSP27 and BAD expression. Free Radic Biol Med, 2012, 52(11–12): 2284-2291

[32] WonJH, ShinJS, ParkHJ, et al.. Anti-inflammatory effects of madecassic acid via the suppression of NF-kappaB pathway in LPS-induced RAW 264.7 macrophage cells. Planta Med, 2010, 76(3): 251-257

[33] DuanPY, MaY, LiXN, et al.. Inhibition of RIPK1-dependent regulated acinar cell necrosis provides protection against acute pancreatitis via the RIPK1/NF-kappaB/AQP8 pathway. Exp Mol Med, 2019, 51(8): 90

[34] MoXJ, YeXZ, LiYP. Effects of euphorbia kansui on the serum levels of IL-6, TNF-alpha, NF-kappaB, sTNFR and IL-8 in patients with severe acute pancreatitis. J Biol Regul Homeost Agents, 2019, 33(2): 469-475

[35] JaworekJ, SzklarczykJ, KotM, et al.. Chemerin alleviates acute pancreatitis in the rat thorough modulation of NF-kappaB signal. Pancreatology, 2019, 19(3): 401-408

[36] WoodfinA, BeyrauM, VoisinMB, et al.. ICAM-1-expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia. Blood, 2016, 127(7): 898-907

[37] LiuJ, WangG, LiuY, et al.. Effects of Somatostatin Combined with Pantoprazole on Serum C-Reactive Protein and Intercellular Adhesion Molecule-1 in Severe Acute Pancreatitis. J Coll Physicians Surg Pak, 2019, 29(7): 683-684

[38] El-AshmawyNE, KhedrNF, El-BahrawyHA, et al.. Anti-inflammatory and Antioxidant Effects of Captopril Compared to Methylprednisolone in L-Arginine-Induced Acute Pancreatitis. Dig Dis Sci, 2018, 63(6): 1497-1505

[39] D’AlessioFR, TsushimaK, AggarwalNR, et al.. Resolution of experimental lung injury by monocyte-derived inducible nitric oxide synthase. J Immunol, 2012, 189(5): 2234-2245

[40] PlociennikowskaA, Hromada-JudyckaA, DembinskaJ, et al.. Contribution of CD14 and TLR4 to changes of the PI(4,5)P2 level in LPS-stimulated cells. J Leukoc Biol, 2016, 100(6): 1363-1373

[41] LiuC, ZhangC, MitchelRE, et al.. A critical role of tolllike receptor 4 (TLR4) and its’ in vivo ligands in basal radio-resistance. Cell Death Dis, 2013, 4: e649

[42] Matas-CobosAM, Redondo-CerezoE, Alegria-MotteC, et al.. The role of Toll-like receptor polymorphisms in acute pancreatitis occurrence and severity. Pancreas, 2015, 44(3): 429-433

[43] HuangL, ZhuH, GuJ. Octreotide and Continuous Hemofiltration versus Continuous Hemofiltration Alone in Severe Acute Pancreatitis Complicated with Acute Respiratory Distress Syndrome. J Coll Physicians Surg Pak, 2019, 29(8): 785-787

[44] JinYH, LiuY. Efficacy of blood purification for severe pancreatitis and acute respiratory distress syndrome. Medicine (Baltimore), 2019, 98(38): e17284