The Effects of Sleeping-inclued Hypoxema at Different Time and Level on Pulmonary Emphysema and of Coagulation System Function in Rats with Pulmonary Emphysema_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YAO Wo ¹ ,  FENG Jing ¹ , WU Qi ¹ , CHEN Baoyuan ¹ , MEN Jianlong ² , RENJing ² , ZHANG Zheli ¹

Respiratory Department of Tianjin Medical University General Hospital. Tianjin，300052，ChinaCorresponding Author: FENG Jing，E-mail : zyyhxkfj@yahoo.com.cn;

Corresponding author：

FENG Jing, Email: zyyhxkfj@yahoo.com.cn

Keywords：

Chronic obstructive pulmonary disease; Pulmonary emphysema; Sleep-induced hypoxemia; Antithrombin Ⅲ; Fibrinogen; von Willebrand factor; Blood coagulation factor Ⅷ

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Objective To investigate whether the sleep-induced hypoxemia ( SIH) at different time and different level have different effects on pulmonary emphysema and coagulation systemfunction in the rats with pulmonary emphysema. Methods Thirty Wistar rats were randomly divided into three groups( n = 10 in each group) . All rats were exposed to cigarette smoke twice a day ( 30 min each time) . From29th day on, the rats in Group A ( pulmonary emphysema with short SIH) were also exposed to mixed gas of 12. 5% oxygen for 1. 5 hours during sleeping time every day ( the expose time was divided into 4 periods, 22. 5 min each) . The rats in Group B ( pulmonary emphysema with mild SIH) were also exposed to mixed gas of 15% oxygen for three hours during sleeping time every day( the expose time was divided into 4 periods, 45 min each) . The rats in Group C( pulmonary emphysema with standard SIH) were also exposed to mixed gas of 12. 5% oxygen for three hours during sleeping time every day( the expose time was divided into 4 periods,45 min each) . After continuous exposure for 56 days, the rats were sacrificed. Semi-quantitative image analytic method was employed for histopathological analysis including pathological score of lungs, mean linear intercept ( MLI) and mean alveolus number( MAN) . ATⅢ, FIB, vWF, FⅧ were measured. Results All animals in three groups manifested the histopathological features of emphysema. Pathological scores of lungs and MLI of every group were significantly different from each other( F = 21. 907, F = 18. 415, all P lt; 0. 05) , Group A [ ( 61. 90 ±4. 25) % , ( 92. 45 ±1. 78) μm] and Group B[ ( 64. 60 ±3. 95) % , ( 92. 80 ±3. 65) μm] were significantly lower than Group C[ ( 73. 30 ±3. 86) % , ( 99. 32 ±2. 81) μm, q= 8. 96, q =6. 84, q = 12. 64, q =9. 65, all P lt; 0. 05] . Levels of FIB were significantly different among three groups ( F = 20. 592, P lt; 0. 05) while FIB in Group A[ ( 189. 98 ±5. 29) mg/ dL] and Group B[ ( 182. 70 ±2. 78) mg /dL] were significantly lower than that in Group C[ ( 198. 40 ±7. 37) mg/ dL, q = 4. 86, q= 9. 07, all P lt; 0. 05] , and FIB in Group A was significantly higher than that in Group B( q = 4. 20, P lt; 0. 05) . Levels of FⅧ were significantly different from each other( F = 33. 652, P lt;0. 05) while FⅧ in Group A[ ( 232. 26 ±4. 17) % ]and Group B[ ( 242. 53 ±14. 50) % ] were significantly lower than that in Group C[ ( 303. 25 ±32. 93) % ,q= 10. 73, q = 9. 18, all P lt; 0. 05] . Conclusions Pulmonary emphysema and hypercoagulable states increases with time and severity of SIH in rats with pulmonary emphysema. The elevated activity of blood coagulation factor may be a critical role in the hypercoagulable states.

Citation： YAO Wo,FENG Jing,WU Qi,CHEN Baoyuan,MEN Jianlong,RENJing,ZHANG Zheli. The Effects of Sleeping-inclued Hypoxema at Different Time and Level on Pulmonary Emphysema and of Coagulation System Function in Rats with Pulmonary Emphysema. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(6): 524-527. doi: Copy

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8.	Orem JM，Lovering AT，Vidruk EH. Excitation of medullary respiratory neurons in REM sleep. Sleep，2005，28: 801-807.
9.	Dahl M，Tybjaerg-Hansen A，Vestbo J，et al. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease. Am J Respir Crit Care Med，2001，164: 1008-1011.
10.	姜正华，吕元文，朱慕云，等. 慢性阻塞性肺疾病患者血气分析与血浆纤维蛋白原的相关性研究. 实用诊断与治疗杂志，2006，20: 13-14.
11.	宋丽娜，董小黎，周以健. 急性缺氧时内皮细胞中vWF的变化. 中华血液学杂志，2000，21: 475-477.
12.	谢飞，王鸿利. 凝血因子Ⅷ结构与功能关系的研究进展. 国外医学临床生物化学与检验学分册，2005，26: 932-939.

1. 中华医学会呼吸病学分会慢性阻塞性肺疾病学组. 慢性阻塞性肺疾病诊治指南（2007年修订版）. 中华结核和呼吸杂志，2007，30: 8-17.
2. Casey KR，Cantillo KO，Brown LK. Sleep-Related Hypoventilation/Hypoxemic Syndromes. Chest，2007，131: 1936-1948.
3. 冯靖，朱宝玉. 慢性阻塞性肺疾病与夜间低氧血症. 国外医学呼吸系统分册，2003，23: 30-33.
4. Ashitani J，Mukae H，Arimura Y，et al. Elevated plasma procoagulant and fibrinolytic markers in patients with chronic obstructive pulmonary disease. Intern Med，2002，41: 181-185.
5. Vernooy JH，Dentener MA，van RJ，et al. Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology. Am J Respir Cell Mol Biol，2002，26: 152-159.
6. Liu F. Receptor-regulated Smads in TGF-beta signaling. Front Biosci，2003，8: S1280-S1303.
7. Nikolaou E，Trakada G，Prodromakis E，et al. Evaluation of Arterial Endothelin-1 Levels，before and during a Sleep Study，in Patients with Bronchial Asthma and Chronic Obstructive Pulmonary Disease. Respiration，2003，70: 606-610.
8. Orem JM，Lovering AT，Vidruk EH. Excitation of medullary respiratory neurons in REM sleep. Sleep，2005，28: 801-807.
9. Dahl M，Tybjaerg-Hansen A，Vestbo J，et al. Elevated plasma fibrinogen associated with reduced pulmonary function and increased risk of chronic obstructive pulmonary disease. Am J Respir Crit Care Med，2001，164: 1008-1011.
10. 姜正华，吕元文，朱慕云，等. 慢性阻塞性肺疾病患者血气分析与血浆纤维蛋白原的相关性研究. 实用诊断与治疗杂志，2006，20: 13-14.
11. 宋丽娜，董小黎，周以健. 急性缺氧时内皮细胞中vWF的变化. 中华血液学杂志，2000，21: 475-477.
12. 谢飞，王鸿利. 凝血因子Ⅷ结构与功能关系的研究进展. 国外医学临床生物化学与检验学分册，2005，26: 932-939.

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