新型氣體信號分子硫化氫對吸煙大鼠氣道炎癥和氣道張力的影響_《中國呼吸與危重監護雜志》

作者：

王配配 ¹ ,  陳亞紅 ¹ , 齊永芬 ² , 王新茂 ¹ , 姚婉貞 ¹ , 唐朝樞 ²

1 北京大學第三醫院呼吸科（北京 100191）;;
2 北京大學醫學部生理系（北京 100191）;

關鍵詞：

硫化氫被動吸煙氣道高反應性氣道炎癥慢性阻塞性肺疾病

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目的探討氣體信號分子硫化氫( H2S) 對被動吸煙大鼠氣道炎癥和氣道反應性的影響。方法 36 只SD 雄性大鼠隨機分為對照組和被動吸煙組, 每組18 只。被動吸煙組給予被動吸入香煙煙霧( CS) 處理, 對照組呼吸清潔空氣。兩組按照處理方式不同[ 腹腔注射生理鹽水、硫氫化鈉( NaHS) 、炔丙基甘氨酸( PPG) ] 相應分別下分為Con 組、NaHS 組和PPG 組, 以及CS組、CS + NaHS組和CS + PPG組。4 個月后取大鼠左肺進行病理學觀察并予評分, 測定各組大鼠氣道反應性, 采用敏感硫電極測定血漿及肺組織H2S 水平, Western blot 測定肺組織胱硫醚γ裂解酶( CSE) 蛋白表達。結果 CS 組肺組織CSE 蛋白表達較Con 組增加( P lt;0. 05) 。與Con 組比較, NaHS 組、CS 組、CS +NaHS 組血漿H2 S含量顯著增高, 而PPG 組明顯降低( P 均 lt; 0. 05) ; 與CS 組比較, CS+NaHS組血漿中H2S 含量顯著增加, 而CS+ PPG 組顯著降低( P 均 lt;0. 05) 。各組大鼠肺組織勻漿中H2S 含量差異無統計學意義。與Con 組比較, CS組大鼠氣道壁炎癥病理評分明顯升高, 氣道對乙酰膽堿( ACh) 和氯化鉀( KCl) 的反應性增高; 與CS 組比較, CS+ NaHS組氣道壁炎癥病理評分降低( P lt;0. 05) , 氣道反應性下降( P lt;0. 05) , 而CS + PPG組氣道壁炎癥病理評分明顯升高( P lt;0. 05) , 氣道反應性進一步升高( P lt;0. 01) 。結論新型氣體信號分子H2S 能夠減輕吸煙導致的氣道炎癥和氣道高反應性, 為內源性保護因子之一。

引用本文： 王配配,陳亞紅,齊永芬,王新茂,姚婉貞,唐朝樞. 新型氣體信號分子硫化氫對吸煙大鼠氣道炎癥和氣道張力的影響. 中國呼吸與危重監護雜志, 2009, 09(4): 327-332. doi: 復制

1.	劉輝國, 徐永健. 慢性阻塞性肺疾病: 從氣道慢性炎癥到全身慢性炎癥. 中國呼吸與危重監護雜志, 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.	閆輝, 杜軍保, 唐朝樞. 自發性高血壓大鼠硫化氫/ 胱硫醚γ裂解酶體系的實驗觀察. 中華醫學雜志, 2004, 84: 1114-1147.
8.	閆輝, 杜軍保, 唐朝樞. 硫化氫對自發性高血壓大鼠主動脈平滑肌細胞增殖與凋亡的影響. 實用兒科臨床雜志, 2004,19: 188-190.
9.	閆輝, 杜軍保, 唐朝樞. 氣體分子硫化氫對自發性高血壓大鼠主動脈結構重建的調節作用. 北京大學學報( 醫學版) , 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.	陳曉波, 杜軍保, 張春雨, 等. 新型氣體信號分子硫化氫對低氧大鼠肺動脈平滑肌細胞凋亡的影響. 北京大學學報( 醫學版) ,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.	金紅芳, 梁晨, 梁嘉敏, 等. 硫化氫對高肺血流性肺動脈高壓大鼠血管炎癥反應的調節作用. 中華醫學雜志, 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. 劉輝國, 徐永健. 慢性阻塞性肺疾病: 從氣道慢性炎癥到全身慢性炎癥. 中國呼吸與危重監護雜志, 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. 閆輝, 杜軍保, 唐朝樞. 自發性高血壓大鼠硫化氫/ 胱硫醚γ裂解酶體系的實驗觀察. 中華醫學雜志, 2004, 84: 1114-1147.
8. 閆輝, 杜軍保, 唐朝樞. 硫化氫對自發性高血壓大鼠主動脈平滑肌細胞增殖與凋亡的影響. 實用兒科臨床雜志, 2004,19: 188-190.
9. 閆輝, 杜軍保, 唐朝樞. 氣體分子硫化氫對自發性高血壓大鼠主動脈結構重建的調節作用. 北京大學學報( 醫學版) , 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. 陳曉波, 杜軍保, 張春雨, 等. 新型氣體信號分子硫化氫對低氧大鼠肺動脈平滑肌細胞凋亡的影響. 北京大學學報( 醫學版) ,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. 金紅芳, 梁晨, 梁嘉敏, 等. 硫化氫對高肺血流性肺動脈高壓大鼠血管炎癥反應的調節作用. 中華醫學雜志, 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.

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