同型半胱氨酸轉硫途徑和維生素B6及內源性硫化氫在慢性阻塞性肺疾病急性加重期的作用_《華西醫學》

作者：

趙麗 ,  文富強 , 左秋南 , 王業 , 陳磊 , 汪濤

四川大學華西醫院呼吸內科（成都，610041）;

關鍵詞：

同型半胱氨酸維生素B6 硫化氫氧化應激慢性阻塞性肺疾病

DOI：

CNKI: 51-1356/R.20120214.1341.014

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目的　研究同型半胱氨酸轉硫途徑、維生素B6及內源性硫化氫在慢性阻塞性肺疾病急性加重期（AECOPD）中的作用。方法　2010年2月－4月間篩選AECOPD患者16例和健康志愿者（對照組）13例，測定AECOPD患者加重期、緩解期及對照組的肺功能、血清硫化氫（H2S）、丙二醛（MDA）、葉酸、維生素B12、C反應蛋白、白介素6、血漿同型半胱氨酸、胱硫醚、半胱氨酸和維生素B6的濃度。計算半胱氨酸轉化率（半胱氨酸濃度/胱硫醚濃度）與胱硫醚轉化率（胱硫醚濃度/同型半胱氨酸濃度）參與分析。結果　 ① 加重期血清MDA水平[（7.3 ± 5.1）nmol/L ]比緩解期[（3.0 ± 1.4）nmol/L ]和對照組[（3.0 ± 2.2）nmol/L ]均升高（P＜0.01）；血清MDA水平與第1秒用力呼氣容積/用力肺活量（FEV1/FVC）、第1秒用力呼氣容積占預計值百分比（FEV1%預計值）呈負相關。② 加重期血清H2S水平與血漿維生素B6水平較緩解期與對照組降低（P＜0.01）；緩解期血清H2S水平[（47.2 ±5.1） μmol/L ]高于對照組[（38.8 ± 2.1） μmol/L ]，P＜0.01；血清H2S水平、血漿維生素B6水平均與FEV1%預計值呈正相關（r=0.651、0.680，P＜0.01），均與血清MDA水平呈負相關（r=-0.334、-0.448，P＜0.05）。③ 加重期半胱氨酸轉化率（3.97 ± 2.41）低于緩解期（5.92 ± 2.18）與對照組（6.14 ± 3.15）差異有統計學意義（P＜0.05）；而胱硫醚轉化率則相反。④ 葉酸與維生素B12水平各組間均無差異。結論　提高AECOPD患者維生素B6及H2S濃度可能能促使AECOPD患者向穩定狀態轉歸，減輕氧化應激損傷。維生素B6與H2S可能成為AECOPD患者的一個新的治療點。
Objective To study the roles of homocysteine (Hcy) transsulfuration pathway, Vitamin B6 and endogenous hydrogen sulfide in treating patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods 　Sixteen AECOPD patients and 13 healthy controls (Control group) from February to April 2010 were recruited in this study. Lung function, serum hydrogen sulfide (H2S), malondialdehyde (MDA), folate, vitamin B12, C-reactive protein (CRP), interleukin-6 (IL-6), Hcy, cystathionine, cystein (Cys) and vitamin B6 were all measured for all the patients in the acute exacerbation period and alleviation period and healthy controls. The conversion rate of Cys (expressed as Cys/cystathionine) and the conversion rate of cystathionine (expressed as cystathionine/Hcy) were calculated for analysis. Results 　Serum MDA level for patients in the acute exacerbation period (AE period) [(7.3 ± 5.1) nmol/L] was significantly higher than that in the alleviation period [(3.0 ± 1.4) nmol/L] and in the healthy controls [(3.0 ± 2.2) nmol/L] (P ＜ 0.01). Serum MDA level was negatively correlated with percentage of FEV1 in predicted FEV1 (FEV1% pred) and FEV1/FVC. Serum H2S level and plasma vitamin B6 level for patients in the AE period were significantly lower than those in the alleviation period and in the healthy controls (P ＜ 0.01), and serum H2S level was significantly higher in the alleviation period [(47.2 ± 5.1) μmol/L] than in the controls [(38.8 ± 2.1) μmol/L] (P ＜ 0.01). Both serum H2S and plasma vitamin B6 levels were correlated positively with FEV1% pred for patients in the AE period and healthy controls (r=0.651, 0.680; P ＜ 0.01), but negatively correlated with serum MDA level (r=-0.334, -0.448; P ＜ 0.05). The conversion rate of Cys for patients in the AE period (3.97 ± 2.41) was significantly lower than that in the alleviation period (5.92 ± 2.18) and the control group (6.14 ± 3.15) (P ＜ 0.05), but the conversion rate of cystathionine was just the opposite (P ＜ 0.05). There were no significant differences in the levels of serum folate and vitamin B12 among the three groups. Conclusion 　Raising the Vitamin B6 and H2S level may facilitate stabilizing of conditions in patients with AECOPD and reduce oxidative stress. Therefore, it may become a new treatment method for AECOPD.

引用本文： 趙麗,文富強,左秋南,王業,陳磊,汪濤. 同型半胱氨酸轉硫途徑和維生素B6及內源性硫化氫在慢性阻塞性肺疾病急性加重期的作用. 華西醫學, 2012, 27(2): 213-217. doi: CNKI: 51-1356/R.20120214.1341.014 復制

1.	Bai N, Khazaei M, Van Eeden SF, et al. The pharmacology of particulate matter air pollution-induced cardiovascular dysfunction[J]. Pharmacol Ther, 2007, 113(1): 16-29.
2.	Baranes PJ. Chronic obstructive pulmonary disease[J]. N Engl J Med, 2000, 343(4): 269-280.
3.	Rangasamy T, Cho CY, Thimmulappa RK, et al. Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice[J]. J Clin Invest, 2004, 114(9): 1248-1259.
4.	Donma O, Donma MM. Relationship of senescence of pulmonary system to chronic obstructive pulmonary disease in the advanced life[J]. Med Hypotheses, 2002, 59(2): 208-211.
5.	Rahman I. Antioxidant therapies in COPD[J]. Int J Chron Obstruct Pulmon Dis, 2006, 1(1): 15-29.
6.	Rahman I, Macnee W. Oxidant/antioxidant imbalance in smokers and chronic obstructive pulmonary diseases[J]. Thorax 1996, 51(4): 348-350.
7.	Ubbink JB, van der Merwe A, Delport R, et al. The Effect of a Subnormal Vitamin B-6 Status on Homocysteine Metabolism[J]. J Clin Invest, 1996, 98 (1): 177-184.
8.	Kai S, Nomura A, Morishima Y, et al. The effect of smoking-related hyperhomocysteinemia on spirometric declines in chronic obstructive pulmonary disease in elderly[J]. Arch Gerontol Geriatr, 2006, 42(2):117-124.
9.	Yan SK, Chang T, Wang H, et al. Effects of hydrogen sulfide on homocysteine-induced oxidative stress in vascular smooth muscle cells[J]. Biochem Biophys Res Commun, 2006, 315(2): 485-491.
10.	Geng BL, Pan CC, Qi Y, et al. Endogenous hydrogen sul?de regulation of myocardial injury induced by isoproterenol[J]. Biochem Biophys Res Commun, 2004, 318(3): 756-763.
11.	Chen YH, Wang PP, Wang XM, et al. Involvement of endogenous hydrogen sul?de in cigarette smoke-induced changes in airway responsiveness and in?ammation of rat lung[J]. Cytokine, 2011, 53(3): 334-341.
12.	Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary[J]. Am J Respir Crit Care Med, 2007, 176(6): 532-555.
13.	Jiang Z, Liang Q, Luo G, et al. HPLC–electrospray tandem mass spectrometry for simultaneous quantitation of eight plasma aminothiols: application to studies of diabetic nephropathy[J]. Talanta, 2009, 77(4): 1279-1284.
14.	Kitano S, Kanno T, Maekawa M, et al. Improved method for the immunological detection of malondialdehyde-modi?ed low-density lipoproteins in human serum[J]. Anal Chim Acta, 2004, 509(2): 229-235.
15.	Zhao WM, Zhang J, Lu YJ, et al. The vasorelaxant effect of H2S as a novel endogenous gaseous Katp channel opener[J].Embo J, 2001, 20(21): 6008-6016.
16.	Gan WQ, Man SF, Senthilselvan A, et al. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis[J]. Thorax, 2004, 59(7): 574-580.
17.	Repine JE, Bast A, Lankhorst I. Oxidative stress in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 1997, 156(2): 341-357.
18.	Robert E, Jemma B, Martin G, et al. Systemic inflammation and COPD[J]. Chest, 2008, 133(1): 19-25.
19.	Kuleci S, Hanta I, Kocabas A, et al. The effect of different treatment modalities on oxidative stress in COPD[J]. Adv Ther, 2008, 25(7): 710-717.
20.	Gumral N, Naziroglu M, Ongel K, et al. Antioxidant enzymes and melatonin levels in patients with bronchial asthma and chronic obstructive pulmonary disease during stable and exacerbation periods[J]. Cell Biochem Funct, 2009, 27(5): 276-283.
21.	Karadag F, C?ldag O, Alt?n?s?k M, et al. Trace elements as a component of oxidative stress in COPD[J]. Respirology, 2004, 9(1): 33-37.
22.	Seemungal TA, Lun JC, Jin HF, et al. Plasma homocysteine is elevated in COPD patients and is related to COPD severity[J]. Int J Chron Obstruct Pulmon Dis, 2007, 2(3): 313-321.
23.	Wei HL, Zhang CY, Jin HF, et al. Hydrogen sulfide regulates lung tissue-oxidized glutathione and total antioxidant capacity in hypoxic pulmonary hypertensive rats[J]. Acta Pharmacologica Sinica, 2008, 29(6): 670-679.

1. Bai N, Khazaei M, Van Eeden SF, et al. The pharmacology of particulate matter air pollution-induced cardiovascular dysfunction[J]. Pharmacol Ther, 2007, 113(1): 16-29.
2. Baranes PJ. Chronic obstructive pulmonary disease[J]. N Engl J Med, 2000, 343(4): 269-280.
3. Rangasamy T, Cho CY, Thimmulappa RK, et al. Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice[J]. J Clin Invest, 2004, 114(9): 1248-1259.
4. Donma O, Donma MM. Relationship of senescence of pulmonary system to chronic obstructive pulmonary disease in the advanced life[J]. Med Hypotheses, 2002, 59(2): 208-211.
5. Rahman I. Antioxidant therapies in COPD[J]. Int J Chron Obstruct Pulmon Dis, 2006, 1(1): 15-29.
6. Rahman I, Macnee W. Oxidant/antioxidant imbalance in smokers and chronic obstructive pulmonary diseases[J]. Thorax 1996, 51(4): 348-350.
7. Ubbink JB, van der Merwe A, Delport R, et al. The Effect of a Subnormal Vitamin B-6 Status on Homocysteine Metabolism[J]. J Clin Invest, 1996, 98 (1): 177-184.
8. Kai S, Nomura A, Morishima Y, et al. The effect of smoking-related hyperhomocysteinemia on spirometric declines in chronic obstructive pulmonary disease in elderly[J]. Arch Gerontol Geriatr, 2006, 42(2):117-124.
9. Yan SK, Chang T, Wang H, et al. Effects of hydrogen sulfide on homocysteine-induced oxidative stress in vascular smooth muscle cells[J]. Biochem Biophys Res Commun, 2006, 315(2): 485-491.
10. Geng BL, Pan CC, Qi Y, et al. Endogenous hydrogen sul?de regulation of myocardial injury induced by isoproterenol[J]. Biochem Biophys Res Commun, 2004, 318(3): 756-763.
11. Chen YH, Wang PP, Wang XM, et al. Involvement of endogenous hydrogen sul?de in cigarette smoke-induced changes in airway responsiveness and in?ammation of rat lung[J]. Cytokine, 2011, 53(3): 334-341.
12. Rabe KF, Hurd S, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary[J]. Am J Respir Crit Care Med, 2007, 176(6): 532-555.
13. Jiang Z, Liang Q, Luo G, et al. HPLC–electrospray tandem mass spectrometry for simultaneous quantitation of eight plasma aminothiols: application to studies of diabetic nephropathy[J]. Talanta, 2009, 77(4): 1279-1284.
14. Kitano S, Kanno T, Maekawa M, et al. Improved method for the immunological detection of malondialdehyde-modi?ed low-density lipoproteins in human serum[J]. Anal Chim Acta, 2004, 509(2): 229-235.
15. Zhao WM, Zhang J, Lu YJ, et al. The vasorelaxant effect of H2S as a novel endogenous gaseous Katp channel opener[J].Embo J, 2001, 20(21): 6008-6016.
16. Gan WQ, Man SF, Senthilselvan A, et al. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis[J]. Thorax, 2004, 59(7): 574-580.
17. Repine JE, Bast A, Lankhorst I. Oxidative stress in chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 1997, 156(2): 341-357.
18. Robert E, Jemma B, Martin G, et al. Systemic inflammation and COPD[J]. Chest, 2008, 133(1): 19-25.
19. Kuleci S, Hanta I, Kocabas A, et al. The effect of different treatment modalities on oxidative stress in COPD[J]. Adv Ther, 2008, 25(7): 710-717.
20. Gumral N, Naziroglu M, Ongel K, et al. Antioxidant enzymes and melatonin levels in patients with bronchial asthma and chronic obstructive pulmonary disease during stable and exacerbation periods[J]. Cell Biochem Funct, 2009, 27(5): 276-283.
21. Karadag F, C?ldag O, Alt?n?s?k M, et al. Trace elements as a component of oxidative stress in COPD[J]. Respirology, 2004, 9(1): 33-37.
22. Seemungal TA, Lun JC, Jin HF, et al. Plasma homocysteine is elevated in COPD patients and is related to COPD severity[J]. Int J Chron Obstruct Pulmon Dis, 2007, 2(3): 313-321.
23. Wei HL, Zhang CY, Jin HF, et al. Hydrogen sulfide regulates lung tissue-oxidized glutathione and total antioxidant capacity in hypoxic pulmonary hypertensive rats[J]. Acta Pharmacologica Sinica, 2008, 29(6): 670-679.

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同型半胱氨酸轉硫途徑和維生素B6及內源性硫化氫在慢性阻塞性肺疾病急性加重期的作用

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同型半胱氨酸轉硫途徑和維生素B6及內源性硫化氫在慢性阻塞性肺疾病急性加重期的作用

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