Protective Effect and Mechanism of Ulinastatin for Ventilation-induced Lung Injury in Rats_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XIAOZheng-hua , GUJun , QINChao-yi , HUJia , FANGZhi ,  MENGWei

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

MENGWei, Email: meng_wei_1111@yahoo.com

Keywords：

Ventilator induced lung injury; High mobility group box-1; Toll like receptor 4; Tumor necrosis factor-α; Interleukin-6

DOI：

10.7507/1007-4848.20160238

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effect and mechanism of ulinastatin to ventilator induced lung injury (VILI). Methods Total 24 SD rats were randomly divided into a control group, a VILI group, and a VILI+ ulinastatin group. High mobility group box-1 (HMGB-1), tumor necrosis factor (TNF)-α and interleukin (IL)-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were detected in the three groups. Results HMGB-1, TNF-α, and IL-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were significantly higher in the VILI group than those in the control group with statistical differences (P<0.05). While HMGB-1, TNF-α, and IL-6 in bronchoalveolar lavage fluid, toll like receptor-4, dry/wet ratio and pathological scores of lung tissue were reduced in the VILI+ ulinastatin group compared with those in the VILI group. Conclusion Ulinastatin may protect ventilator induced lung injury by reducing inflammation level in lung through HMGB-1-TLR4 pathway.

Citation： XIAO Zheng-hua, GU Jun, QIN Chao-yi, HU Jia, FANG Zhi, MENG Wei. Protective Effect and Mechanism of Ulinastatin for Ventilation-induced Lung Injury in Rats. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2016, 23(10): 1001-1005. doi: 10.7507/1007-4848.20160238 Copy

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10.	Xiong XQ, Lin LN, LR. Wang, et al. Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in miceJ. Int J Nanomedicine, 2013, 6: 1075-81.
11.	Ma H, Feng X, Ding S. Hesperetin attenuates ventilator-induced acute lung injury through inhibition of NF-kappaB-mediated inflammation. Eur J Pharmacol, 2015, 769: 333-341.
12.	Gattinoni L, D'Andrea L, Pelosi P, et al. Regional effects and mechanism of positive end-expiratory pressure in early adult respiratory distress syndrome. JAMA, 1993, 269(16): 2122-2127.
13.	Pinhu L, Whitehead T, Evans T, et al. Ventilator-associated lung injury. Lancet, 2003, 361(9354): 332-340.
14.	Belperio JA, Keane MP, Burdick MD, et al. Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury. J Clin Invest, 2002, 110(11): 1703-1716.
15.	Andersson U, Antoine DJ, Tracey KJ. The functions of HMGB1 depend on molecular localization and post-translational modifications. J Intern Med, 2014, 276(5): 420-424.
16.	Pilzweger C, Holdenrieder S. Circulating HMGB1 and RAGE as clinical biomarkers in malignant and autoimmune diseases. Diagnostics (Basel), 2015, 5(2): 219-253.
17.	Ohndorf UM, Rould MA, He Q, et al. Basis for recognition of cisplatin-modified DNA by high-mobility-group proteins. Nature, 1999, 399(6737): 708-712.
18.	18 Anton M, Alen F, Gomez de Heras R, et al. Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration. Addict Biol, 2016, doi: 10.1111/adb.12365.[Epubaheadofprint].
19.	Saigal S, Kapoor G. Ulinastatin: is it worth using in severe sepsis. Intensive Care Med, 2014, 40(8): 1185.
20.	Wang SY, Li ZJ, Wang X, et al. Effect of ulinastatin on HMGB1 expression in rats with acute lung injury induced by sepsis. Genet Mol Res, 2015, 14(2): 4344-4353.

1. Sutherasan Y, D'Antini D, Pelosi P. Advances in ventilator-associated lung injury: prevention is the target. Expert Rev Respir Med, 2014, 8(2): 233-248.
2. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med, 2000, 342(18): 1301-1308.
3. Muller-Redetzky HC, Felten M, Hellwig K, et al. Increasing the inspiratory time and I:E ratio during mechanical ventilation aggravates ventilator-induced lung injury in mice. Crit Care, 2015, 19 (1): 23.
4. Damas P, Frippiat F, Ancion A, et al. Prevention of ventilator-associated pneumonia and ventilator-associated conditions: a randomized controlled trial with subglottic secretion suctioning. Crit Care Med, 2015, 43(1): 22-30.
5. Muscedere J, Sinuff T, Heyland DK, et al. The clinical impact and preventability of ventilator-associated conditions in critically ill patients who are mechanically ventilatedJ. Chest, 2013, 144(5): 1453-1460.
6. Fang XZ, Huang TF, Wang CJ, et al. Preconditioning of physiological cyclic stretch attenuated HMGB1 expression in pathologically mechanical stretch-activated A549 cells and ventilator-induced lung injury rats through inhibition of IL-6/STAT3/SOCS3J. Int Immunopharmacol, 2015, 31: 66-73.
7. 潘成, 虞惠康, 罗月娥. 注射用乌司他丁. 中国新药杂志, 2000, 9(2): 123-124.
8. 姜兴权, 王育珊, 奭骥, 等. 急性肺损伤肺保护性通气乌司他丁干预的临床研究. 中国急救医学, 2006, 26(3): 161-163.
9. Qi M, Zheng L, Qi Y, et al. Dioscin attenuates renal ischemia/reperfusion injury by inhibiting the TLR4/MyD88 signaling pathway via up-regulation of HSP70. Pharmacol Res, 2015, 100: 341-352.
10. Xiong XQ, Lin LN, LR. Wang, et al. Sevoflurane attenuates pulmonary inflammation and ventilator-induced lung injury by upregulation of HO-1 mRNA expression in miceJ. Int J Nanomedicine, 2013, 6: 1075-81.
11. Ma H, Feng X, Ding S. Hesperetin attenuates ventilator-induced acute lung injury through inhibition of NF-kappaB-mediated inflammation. Eur J Pharmacol, 2015, 769: 333-341.
12. Gattinoni L, D'Andrea L, Pelosi P, et al. Regional effects and mechanism of positive end-expiratory pressure in early adult respiratory distress syndrome. JAMA, 1993, 269(16): 2122-2127.
13. Pinhu L, Whitehead T, Evans T, et al. Ventilator-associated lung injury. Lancet, 2003, 361(9354): 332-340.
14. Belperio JA, Keane MP, Burdick MD, et al. Critical role for CXCR2 and CXCR2 ligands during the pathogenesis of ventilator-induced lung injury. J Clin Invest, 2002, 110(11): 1703-1716.
15. Andersson U, Antoine DJ, Tracey KJ. The functions of HMGB1 depend on molecular localization and post-translational modifications. J Intern Med, 2014, 276(5): 420-424.
16. Pilzweger C, Holdenrieder S. Circulating HMGB1 and RAGE as clinical biomarkers in malignant and autoimmune diseases. Diagnostics (Basel), 2015, 5(2): 219-253.
17. Ohndorf UM, Rould MA, He Q, et al. Basis for recognition of cisplatin-modified DNA by high-mobility-group proteins. Nature, 1999, 399(6737): 708-712.
18. 18 Anton M, Alen F, Gomez de Heras R, et al. Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration. Addict Biol, 2016, doi: 10.1111/adb.12365.[Epubaheadofprint].
19. Saigal S, Kapoor G. Ulinastatin: is it worth using in severe sepsis. Intensive Care Med, 2014, 40(8): 1185.
20. Wang SY, Li ZJ, Wang X, et al. Effect of ulinastatin on HMGB1 expression in rats with acute lung injury induced by sepsis. Genet Mol Res, 2015, 14(2): 4344-4353.

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Protective Effect and Mechanism of Ulinastatin for Ventilation-induced Lung Injury in Rats

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