Effects of Tiotropium Bromide on Inflammatory Factors in Serum, BALF and Lung Tissue of COPD Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZhangJinmei ,  SunLihua , GuWei , TanYan , FangSurong

Department of Respiratory Medicine, Nanjing Hospital Affiliated to Nanjing Medical University(Nanjing First Hospital), Nanjing, Jiangsu, 210006, China;

Corresponding author：

SunLihua, Email: nfhsun@sina.com

Keywords：

Tiotropium bromide; Chronic obstructive pulmonary disease; Rats; Inflammatory factors

DOI：

10.7507/1671-6205.2014115

Video：

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Objective To investigate the changes of interleukin-8 (IL-8), tumor necrosis factor-α(TNF-α) and phospholipase A2 (PLA2) in serum, bronchoalveolar lavage fluid (BALF) and lung tissue of COPD rats and the effects of tiotropium.To identify the anti-inflammatory function of tiotropium. Methods Rat COPD model was established by passive smoking as well as intratracheal instillation of lipopolysaccharide(LPS).Thirty male SD rats were randomly divided into a control group, a COPD group and a tiotropium bromide treatment group (n=10 in each group).The pathologic changes of the lung tissue and airway were observed by HE staining.The total and differential cell counts in BALF were observed.The levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue were measured by enzyme-linked immunosorbent assay. Results HE staining revealed that the rat COPD model was successfully established.The COPD group appeared obvious emphysema, while the treatment group appeared mild emphysema.The total inflammatory cells, the proportion of neutrophils and lymphocyte, and the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue in the COPD group were obviously higher than those in the control group (P < 0.01).The total inflammatory cells, the proportion of neutrophils and lymphocyte, and the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue in the treatment group were significantly lower than those in the COPD group but higher than those in the control group (P < 0.01). Conclusions Tiotropium bromide can reduce the levels of IL-8, TNF-α, PLA2 in serum, BALF and lung tissue of COPD rats by reducing the leakage of inflammatory cells, and alleviate the airway inflammation and the degree of emphysema.

Citation： ZhangJinmei, SunLihua, GuWei, TanYan, FangSurong. Effects of Tiotropium Bromide on Inflammatory Factors in Serum, BALF and Lung Tissue of COPD Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2014, 13(5): 469-473. doi: 10.7507/1671-6205.2014115 Copy

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4.	李红梅, 崔德健, 佟欣, 等.熏香烟加气管注内毒素和单纯熏香烟法建立大鼠COPD模型.中国病理生理杂志, 2002:808-812.
5.	管小俊.肺内输入骨髓间充质干细胞对肺气肿大鼠慢性炎症的调控.中国呼吸与危重监护杂志, 2011, 10:520-526.
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7.	田春燕, 张继红, 李伟国, 等.细胞因子与COPD炎症机制研究进展.临床肺科杂志, 2011, 16:248-249.
8.	吴纪珍, 马利军, 李素云, 等.慢性阻塞性肺疾病发作期与缓解期体内胶原、细胞因子变化及临床意义.中国实用内科杂志, 2005, 25:703-704.
9.	陈丽, 刘升明.慢性阻塞性肺疾病的气道炎症及治疗新进展.实用医学杂志, 2008:4170-4171.
10.	Pourfarzam S, Ghazanfari T, Yaraee R, et al.Serum levels of IL-8 and IL-6 in the long term pulmonary complications induced by sulfur mustard:Sardasht-Iran Cohort Study.Int Immunopharmacol, 2009, 9:1482-1488.
11.	王红阳, 赵雪峰, 李球兵, 等.COPD及其吸烟患者IL-8、TNF-α、hsCRP的检测及意义.山东医药, 2007, 47:42-44.
12.	Wood LG, Gibson PG, Garg ML.Biomarkers of lipid peroxidation, airway inflammation and asthma.Eur Respir J, 2003, 21:177-186.
13.	Churg A, Dai J, Tai H, et al.Tumor necrosis factor-alpha is central to acute cigarette smoke-induced inflammation and connective tissue breakdown.Am J Respir Crit Care Med, 2002, 166:849-854.
14.	Mayer RJ, Marshall LA.New insights on mammalian phospholipase A2(s), comparison of arachidonoyl-selective and-nonselective enzymes.FASEB J, 1993, 7:339-348.
15.	Kim DK, Fukuda T, Thompson BT, et al.Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome.Am J Physiol, 1995, 269(1 Pt 1):L109-L118.
16.	Currie GP, Rossiter C, Miles SA, et al.Effects of tiotropium and other long acting bronchodilators in chronic obstructive pulmonary disease.Pulm Pharmacol Ther, 2006, 19:112-119.
17.	李莉芳, 李建强.噻托溴铵在慢性阻塞性肺疾病大鼠模型气道炎症和重塑中的保护作用.山西医药杂志, 2008, 37:103-104.

1. Hanania NA, Marciniuk DD.A unified front against COPD:clinical practice guidelines from the American College of Physicians, the American College of Chest Physicians, the American Thoracic Society, and the European Respiratory Society.Chest, 2011, 140:565-566.
2. 何牡丹, 荣令, 周新.噻托溴铵在COPD大鼠气道炎症中的作用.中国呼吸与危重监护杂志, 2009, 8:212-215.
3. 单淑香, 陈宝元.慢性阻塞性肺疾病患者诱导痰中白介素8、白三烯B4、髓过氧化物酶的变化以及噻托溴铵对其的影响.国际呼吸杂志, 2010, 30:1153-1156.
4. 李红梅, 崔德健, 佟欣, 等.熏香烟加气管注内毒素和单纯熏香烟法建立大鼠COPD模型.中国病理生理杂志, 2002:808-812.
5. 管小俊.肺内输入骨髓间充质干细胞对肺气肿大鼠慢性炎症的调控.中国呼吸与危重监护杂志, 2011, 10:520-526.
6. 高洁, 王旭红, 陈茜.皱肺平喘胶囊对COPD大鼠血清IL-8和TNF-α表达的影响.陕西中医, 2009:1551-1553.
7. 田春燕, 张继红, 李伟国, 等.细胞因子与COPD炎症机制研究进展.临床肺科杂志, 2011, 16:248-249.
8. 吴纪珍, 马利军, 李素云, 等.慢性阻塞性肺疾病发作期与缓解期体内胶原、细胞因子变化及临床意义.中国实用内科杂志, 2005, 25:703-704.
9. 陈丽, 刘升明.慢性阻塞性肺疾病的气道炎症及治疗新进展.实用医学杂志, 2008:4170-4171.
10. Pourfarzam S, Ghazanfari T, Yaraee R, et al.Serum levels of IL-8 and IL-6 in the long term pulmonary complications induced by sulfur mustard:Sardasht-Iran Cohort Study.Int Immunopharmacol, 2009, 9:1482-1488.
11. 王红阳, 赵雪峰, 李球兵, 等.COPD及其吸烟患者IL-8、TNF-α、hsCRP的检测及意义.山东医药, 2007, 47:42-44.
12. Wood LG, Gibson PG, Garg ML.Biomarkers of lipid peroxidation, airway inflammation and asthma.Eur Respir J, 2003, 21:177-186.
13. Churg A, Dai J, Tai H, et al.Tumor necrosis factor-alpha is central to acute cigarette smoke-induced inflammation and connective tissue breakdown.Am J Respir Crit Care Med, 2002, 166:849-854.
14. Mayer RJ, Marshall LA.New insights on mammalian phospholipase A2(s), comparison of arachidonoyl-selective and-nonselective enzymes.FASEB J, 1993, 7:339-348.
15. Kim DK, Fukuda T, Thompson BT, et al.Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome.Am J Physiol, 1995, 269(1 Pt 1):L109-L118.
16. Currie GP, Rossiter C, Miles SA, et al.Effects of tiotropium and other long acting bronchodilators in chronic obstructive pulmonary disease.Pulm Pharmacol Ther, 2006, 19:112-119.
17. 李莉芳, 李建强.噻托溴铵在慢性阻塞性肺疾病大鼠模型气道炎症和重塑中的保护作用.山西医药杂志, 2008, 37:103-104.

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Effects of Tiotropium Bromide on Inflammatory Factors in Serum, BALF and Lung Tissue of COPD Rats

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