Role of Endogenous Hydrogen Sulfide in Airway Inflammation and Airway Responsiveness in a Rat Model of Chronic Passive-Smoking_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

WANGPeipei ¹ ,  CHEN Yahong ¹ , QI Yongfen ² , WANG Xinmao ¹ , YAO Wanzhen ¹ , TANG Chaoshu. ²

Department of Respiratory Medicine, The Third Hospital, Peking University.Beijing, 100191, China;

Corresponding author：

CHEN Yahong, Email: chenyahong@vip.sina.com

Keywords：

Hydrogen sulfide; Passive smoking; Airway hyperresponsiveness; Airway inflammation; Chronic obstructive pulmonary disease

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the role of endogenous Hydrogen Sulfide ( H2S) in airway inflammation and responsiveness in a rat model of chronic passive-smoking. Methods Male SD rats were randomly divided into a control group ( breathing fresh air) and a passive smoking group [ cigarette smoking( CS) passively] , with 18 rats in each group. Six rats in each group were randomly intraperitoneally injected with normal saline, sodium hydrosulfide ( NaHS) or propargylglycine ( PPG, an irreversible inhibitor of cystathionine- γ-lyase) . The animals were divided into six subgroups, ie. Con group, NaHS group, and PPG group, CS group, CS+ NaHS group, and CS + PPG group. After 4 months, lung histological change and airway tension were measured. The H2S levels of plasma and lung tissue were analyzed by the sensitive sulphur electrode assay. The expression of cystathionine-γ-lyase ( CSE) was measured by western blot. Results Compared with the Con group, CSE protein expression in lung tissues was increased in CS group( P lt;0. 05) ; the H2 S levels of plasma were significantly higher in CS group, NaHS group and CS + NaHS group, and much lower in PPG group ( P lt; 0. 05, respectively) . Compared with CS group, the H2S levels of plasma were significantly higher in CS + NaHS group, and much lower in CS + PPG group( P lt; 0. 05, respectively) . The H2S level of lung tissue in each group had no significant difference ( P gt; 0. 05) . Compared with Con group,score of lung pathology was significant elevated, and the responsiveness of airway smooth muscles to ACh and KCl was significant augmented in CS group. Compared with CS group, the score of lung pathology was decreased, and the responsiveness of airway smooth muscles was decreased in CS +NaHS group( P lt;0. 05) , and vise versa in CS + PPG group( P lt; 0. 01) . Conclusion H2S can alleviate airway inflammation and hyperresponsiveness induced by CS, and administration of H2S might be of clinical benefit in airwayinflammation and airway responsiveness.

Citation： WANGPeipei,CHEN Yahong,QI Yongfen,WANG Xinmao,YAO Wanzhen,TANG Chaoshu.. Role of Endogenous Hydrogen Sulfide in Airway Inflammation and Airway Responsiveness in a Rat Model of Chronic Passive-Smoking. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(4): 327-332. doi: Copy

1.	刘辉国, 徐永健. 慢性阻塞性肺疾病: 从气道慢性炎症到全身慢性炎症. 中国呼吸与危重监护杂志, 2007, 6: 410-412.
2.	WangR.Two‘s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J, 2002, 16: 1792-1798.
3.	Chen YH, Yao WZ, Geng B, et al. Endogenous hydrogen sulfide in patients with COPD. Chest, 2005, 128: 3205-3211.
4.	Chen YH, Wu R, Geng B, et al. Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat model of asthma. Cytokine, 2009, 45: 117-123.
5.	Chunyu Z, Junbao D, Dingfang B, et al. The regulatory effect of hydrogen sulfide on hypoxic pulmonary hypertension in rats.Biochem Biophys Res Commun, 2003, 302: 810-816.
6.	Cosio M, Ghezzo H, Hogg JC, et al. The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med, 1978, 298: 1277- 1281.
7.	闫辉, 杜军保, 唐朝枢. 自发性高血压大鼠硫化氢/ 胱硫醚γ裂解酶体系的实验观察. 中华医学杂志, 2004, 84: 1114-1147.
8.	闫辉, 杜军保, 唐朝枢. 硫化氢对自发性高血压大鼠主动脉平滑肌细胞增殖与凋亡的影响. 实用儿科临床杂志, 2004,19: 188-190.
9.	闫辉, 杜军保, 唐朝枢. 气体分子硫化氢对自发性高血压大鼠主动脉结构重建的调节作用. 北京大学学报( 医学版) , 2004, 36:234-237.
10.	Xiaohui L, Junbao D, Lin S, et al. Down-regulation of endogenous hydrogen sulfide pathway in pulmonary hypertension and pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats. Circ J, 2005, 69: 1418-1424.
11.	陈晓波, 杜军保, 张春雨, 等. 新型气体信号分子硫化氢对低氧大鼠肺动脉平滑肌细胞凋亡的影响. 北京大学学报( 医学版) ,2004, 36: 341-344.
12.	Fiorucci S, Antonelli E, Distrutti E, et al. Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs. Gastroenterology, 2005, 129: 1210-1224.
13.	Zanardo RC, Brancaleone V, Distrutti E, et al. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation.FASEB J, 2006, 20: 2118-2120.
14.	Li L, Rossoni G, Sparatore A, et al. Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative. Free Radic Biol Med, 2007 , 42 : 706-719.
15.	Wallace JL, Dicay M, McKnightW, et al. Hydrogen sulfide enhances ulcer healing in rats. FASEB J, 2007, 21: 4070-4076.
16.	金红芳, 梁晨, 梁嘉敏, 等. 硫化氢对高肺血流性肺动脉高压大鼠血管炎症反应的调节作用. 中华医学杂志, 2008, 32: 2235-2239.
17.	Esechie A, Kiss L, Olah G, et al. Protective effect of hydrogen sulfide in a murine model of acute lung injury induced by combined burn and smoke inhalation. Clin Sci ( Lond) , 2008, 115: 91-97.
18.	Bhatia M, Wong FL, Fu D, et al. Role of hydrogen sulfide in acute pancreatitis and associated lung injury. FASEB J,2005, 19: 623-625.
19.	Collin M, Anuar FB, Murch O, et al. Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia. Br J Pharmacol, 2005, 146: 498-505.
20.	Zhang H, Zhi L,Moore PK, et al. Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse. Am J Physiol Lung Cell Mol Physiol, 2006, 290: L1193-L1201.
21.	Zhang H, Zhi L,Moochhala SM, et al. Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and punctureinduced sepsis. J Leukoc Biol, 2007, 82: 894-905.
22.	Zhang H, Bhatia M. Hydrogen sulfide: a novel mediator of leukocyte activation. Immunopharmacol Immunotoxicol, 2008, 30: 631-645.] 23 Bhatia M, Sidhapuriwala JN, Ng SW, et al. Pro-inflammatory effects of hydrogen sulphide on substance P in caerulein-induced acute pancreatitis. J Cell Mol Med, 2008, 12: 580-590.
23.	Kawabata A, Ishiki T, Nagasawa K, et al. Hydrogen sulfide as a novel nociceptive messenger. Pain, 2007, 132: 74-81.
24.	Zhao W, Zhang J, Lu Y, et al. The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J, 2001 ,20: 6008-6016.
25.	Cheng Y, Ndisang JF, Tang G, et al. Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. Am J Physiol Heart Circ Physiol, 2004, 287: H2316-H2323.
26.	Dombkowski RA, Doellman MM, Head SK, et al. Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder smooth muscle. J Exp Biol, 2006, 209: 3234-3240.
27.	Srilatha B, Adaikan PG, Li L, et al. Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function. J Sex Med,2007, 4: 1304-1311.
28.	Teague B, Asiedu S, Moore PK. The smooth muscle relaxant effect of hydrogen sulphide in vitro: Evidence for a physiological role to control intestinal contractility. Br J Pharmacol, 2002, 137 : 139-145.
29.	Hosoki R, Matsuki N, Kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun, 1997, 237: 527-531.
30.	Lee SW, Cheng Y, Moore PK, et al. Hydrogen sulphide regulates intracellular pH in vascular smooth muscle cells. Biochem Biophys Res Commun, 2007, 358: 1142-1147.
31.	Zhao W, Wang R. H2S-induced vasorelaxant and the underlying cellular and molecular mechanisms. Am J Physiol Heart Circ Physiol, 2002 , 283: H474-H480.

1. 刘辉国, 徐永健. 慢性阻塞性肺疾病: 从气道慢性炎症到全身慢性炎症. 中国呼吸与危重监护杂志, 2007, 6: 410-412.
2. WangR.Two‘s company, three’s a crowd: can H2S be the third endogenous gaseous transmitter? FASEB J, 2002, 16: 1792-1798.
3. Chen YH, Yao WZ, Geng B, et al. Endogenous hydrogen sulfide in patients with COPD. Chest, 2005, 128: 3205-3211.
4. Chen YH, Wu R, Geng B, et al. Endogenous hydrogen sulfide reduces airway inflammation and remodeling in a rat model of asthma. Cytokine, 2009, 45: 117-123.
5. Chunyu Z, Junbao D, Dingfang B, et al. The regulatory effect of hydrogen sulfide on hypoxic pulmonary hypertension in rats.Biochem Biophys Res Commun, 2003, 302: 810-816.
6. Cosio M, Ghezzo H, Hogg JC, et al. The relations between structural changes in small airways and pulmonary-function tests. N Engl J Med, 1978, 298: 1277- 1281.
7. 闫辉, 杜军保, 唐朝枢. 自发性高血压大鼠硫化氢/ 胱硫醚γ裂解酶体系的实验观察. 中华医学杂志, 2004, 84: 1114-1147.
8. 闫辉, 杜军保, 唐朝枢. 硫化氢对自发性高血压大鼠主动脉平滑肌细胞增殖与凋亡的影响. 实用儿科临床杂志, 2004,19: 188-190.
9. 闫辉, 杜军保, 唐朝枢. 气体分子硫化氢对自发性高血压大鼠主动脉结构重建的调节作用. 北京大学学报( 医学版) , 2004, 36:234-237.
10. Xiaohui L, Junbao D, Lin S, et al. Down-regulation of endogenous hydrogen sulfide pathway in pulmonary hypertension and pulmonary vascular structural remodeling induced by high pulmonary blood flow in rats. Circ J, 2005, 69: 1418-1424.
11. 陈晓波, 杜军保, 张春雨, 等. 新型气体信号分子硫化氢对低氧大鼠肺动脉平滑肌细胞凋亡的影响. 北京大学学报( 医学版) ,2004, 36: 341-344.
12. Fiorucci S, Antonelli E, Distrutti E, et al. Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs. Gastroenterology, 2005, 129: 1210-1224.
13. Zanardo RC, Brancaleone V, Distrutti E, et al. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation.FASEB J, 2006, 20: 2118-2120.
14. Li L, Rossoni G, Sparatore A, et al. Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative. Free Radic Biol Med, 2007 , 42 : 706-719.
15. Wallace JL, Dicay M, McKnightW, et al. Hydrogen sulfide enhances ulcer healing in rats. FASEB J, 2007, 21: 4070-4076.
16. 金红芳, 梁晨, 梁嘉敏, 等. 硫化氢对高肺血流性肺动脉高压大鼠血管炎症反应的调节作用. 中华医学杂志, 2008, 32: 2235-2239.
17. Esechie A, Kiss L, Olah G, et al. Protective effect of hydrogen sulfide in a murine model of acute lung injury induced by combined burn and smoke inhalation. Clin Sci ( Lond) , 2008, 115: 91-97.
18. Bhatia M, Wong FL, Fu D, et al. Role of hydrogen sulfide in acute pancreatitis and associated lung injury. FASEB J,2005, 19: 623-625.
19. Collin M, Anuar FB, Murch O, et al. Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia. Br J Pharmacol, 2005, 146: 498-505.
20. Zhang H, Zhi L,Moore PK, et al. Role of hydrogen sulfide in cecal ligation and puncture-induced sepsis in the mouse. Am J Physiol Lung Cell Mol Physiol, 2006, 290: L1193-L1201.
21. Zhang H, Zhi L,Moochhala SM, et al. Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and punctureinduced sepsis. J Leukoc Biol, 2007, 82: 894-905.
22. Zhang H, Bhatia M. Hydrogen sulfide: a novel mediator of leukocyte activation. Immunopharmacol Immunotoxicol, 2008, 30: 631-645.] 23 Bhatia M, Sidhapuriwala JN, Ng SW, et al. Pro-inflammatory effects of hydrogen sulphide on substance P in caerulein-induced acute pancreatitis. J Cell Mol Med, 2008, 12: 580-590.
23. Kawabata A, Ishiki T, Nagasawa K, et al. Hydrogen sulfide as a novel nociceptive messenger. Pain, 2007, 132: 74-81.
24. Zhao W, Zhang J, Lu Y, et al. The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener. EMBO J, 2001 ,20: 6008-6016.
25. Cheng Y, Ndisang JF, Tang G, et al. Hydrogen sulfide-induced relaxation of resistance mesenteric artery beds of rats. Am J Physiol Heart Circ Physiol, 2004, 287: H2316-H2323.
26. Dombkowski RA, Doellman MM, Head SK, et al. Hydrogen sulfide mediates hypoxia-induced relaxation of trout urinary bladder smooth muscle. J Exp Biol, 2006, 209: 3234-3240.
27. Srilatha B, Adaikan PG, Li L, et al. Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function. J Sex Med,2007, 4: 1304-1311.
28. Teague B, Asiedu S, Moore PK. The smooth muscle relaxant effect of hydrogen sulphide in vitro: Evidence for a physiological role to control intestinal contractility. Br J Pharmacol, 2002, 137 : 139-145.
29. Hosoki R, Matsuki N, Kimura H. The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. Biochem Biophys Res Commun, 1997, 237: 527-531.
30. Lee SW, Cheng Y, Moore PK, et al. Hydrogen sulphide regulates intracellular pH in vascular smooth muscle cells. Biochem Biophys Res Commun, 2007, 358: 1142-1147.
31. Zhao W, Wang R. H2S-induced vasorelaxant and the underlying cellular and molecular mechanisms. Am J Physiol Heart Circ Physiol, 2002 , 283: H474-H480.

Next Article
From Trunk to Leaves: Exploration and Practice of Conformity in Eight Years’Medical Education Courses

Chinese Journal of Respiratory and Critical Care Medicine

Role of Endogenous Hydrogen Sulfide in Airway Inflammation and Airway Responsiveness in a Rat Model of Chronic Passive-Smoking

Abstract Full text Figures/Tables Video References Cited by

Next Article

Format

Content