Experimental observation of cluster therapeutic regimen in early stage of blast-induced acute lung injury in rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

SU Shizhen ,  LAI Guoxiang , ZHANG Lei , PAN Jianguang

Department of Respiratory and Critical Care Medicine, Fuzhou General Hospital, Fujian Medical University, Fuzhou, Fujian 350025, P. R. China;

Corresponding?author：

LAI Guoxiang, Email: laiguoxiang2007@163.com

Keywords：

Blast injury; Acute lung injury; Ambroxol; Dexamethasone; Anisodamine; Cluster therapeutic regimen

DOI：

10.7507/1671-6205.201806050

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Objective To observe the effects of cluster therapy combined with anisodamine, dexamethasone and ambroxol on arterial blood gas, inflammatory cytokines and pulmonary pathological changes by making an early (<48 h) primary blast lung injury model in rats. Methods Eighty Wistar rats were randomly divided into six groups, ie. a control group (n=5), an injury group (n=15), an ambroxol treatment group (n=15), a dexamethasone treatment group, a scopolamine treatment group (n=15), a combination of ambroxol, dexamethasone and anisodamine group (n=15). The treatment groups were injected intraperitoneally with ambroxol 46.7 mg/kg (three times a day) or (and) dexamethasone at 5 mg·kg^–1·d^–1 or (and) anisodamine at a dose of 3.33 mg/kg (three times a day). The rats in the injury group were injected intraperitoneally with an equal volume of normal saline. Respiratory rate and weight change were observed before and after injury. Five rats were sacrificed at 6 hours, 24 hours and 48 hours after injury in each experimental group. Arterial blood gas analysis, Yelverton pathological score, lung tissue wet/dry weight ratio, serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured. The lung histopathology was observed. Results After lung blast injury, the rats in the injury group showed progressive respiratory acidosis, and hypoxemia increased with the increase of IL-6 and TNF-α in a time-dependent manner. The PaO₂ decreased in the groups with ambroxol, dexamethasone and anisodamine alone or in combination with anisodamine, and the contents of serum IL-6 and TNF-α decreased. Pathological edema and inflammatory infiltration of lung tissue were alleviated significantly. Conclusions After treatment with dexamethasone, anisodamine and ambroxol after lung blast injury, blood gas analysis is improved, inflammatory factor level is decreased and lung injury is alleviated, indicating that the three drugs can treat lung detonation injury in rats. The cluster therapy is superior to the single drug therapy.

Citation： SU Shizhen, LAI Guoxiang, ZHANG Lei, PAN Jianguang. Experimental observation of cluster therapeutic regimen in early stage of blast-induced acute lung injury in rats. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(1): 57-64. doi: 10.7507/1671-6205.201806050 Copy

1.	Ritenour AE, Baskin TW. Primary blast injury: update on diagnosis and treatment. Crit Care Med, 2008, 36(7 Suppl): S311-S317.
2.	Smith JE. The epidemiology of blast lung injury during recent military conflicts: a retrospective database review of cases presenting to deployed military hospitals, 2003-2009. Philos Trans R Soc Lond B Biol Sci, 2011, 366(1562): 291-294.
3.	Avidan V, Hersch M, Armon Y, et al. Blast lung injury: clinical manifestations treatment and outcome. Am J Surg, 2005, 190(6): 927-931.
4.	Chavko M, Prusaczyk WK, McCarron RM. Lung injury and recovery after exposure to blast overpressure. J Trauma, 2006, 61(4): 933-942.
5.	Yelveton JT. Pathology scoring system for blast injuries. J Trauma, 1996, 40(3 Suppl): S111-S115.
6.	Kirkman E, Watts S, Cooper G. Blast injury research models. Philos Trans R Soc Lond B Biol Sci, 2011, 366(1562): 144-159.
7.	Smith JE. Blast lung injury. J R Nav Med Serv, 2011, 97(3): 99-105.
8.	徐立, 金海. 大鼠肺爆震傷模型的建立與傷情分析. 海軍醫學雜志, 2016, 37(1): 9-26.
9.	范崇熙, 張志培, 程慶書, 等. 胸部爆震傷致兔急性呼吸窘迫綜合征模型的建立及相關因素分析. 中國危重病急救醫學雜志, 2011, 23(4): 243-246.
10.	吳山, 孫明, 郭金東, 等. 大鼠肺爆震傷模型的建立和病理變化觀察. 黑龍江醫藥科學, 2001, 24(1): 28-29.
11.	楊衛忠. 肺爆震傷大鼠肺泡上皮細胞通透性改變與 Claudin4 蛋白的表達研究［D］. 山西醫科大學, 2014.
12.	侯曉彬, 李廷慧, 金文波, 等. 地塞米松和山莨菪堿在胸部爆炸傷致急性肺損傷中的防治作用. 中國急救醫學, 2008, 28(6): 531-535.
13.	王靜, 秦霞, 孟偉正. 模擬礦坑瓦斯爆炸致肺部損傷動物實驗模型的建立. 中華實驗外科雜志, 2016, 33(8): 1965.
14.	付澤軍, 李強. 大鼠肺爆震傷簡易模型建立研究. 山西醫科大學學報, 2015, 46(5): 497-498.
15.	付澤軍, 劉龍, 楊衛忠, 等. 緊密連接蛋白 claudin1、3、4 與肺爆震傷致大鼠肺水腫的關系研究. 醫學研究雜志, 2015, 44(11): 31-34.
16.	潘建光, 賴國祥, 文文, 等. 利用簡易三通管路建立大鼠肺爆震傷模型的實驗方法. 醫學研究所學報, 2018, 31(4): 412-415.
17.	雷晉, 段鵬, 郝振明, 等. 成批爆炸燒沖復合傷的救治. 中華損傷與修復雜志 (電子版), 2015, 10(3): 33-36.
18.	Chavko M, Adeeb S, Ahlers ST, et al. Attenuation of pulmonary inflammation after exposure to blast overpressure by N-acetylcysteine amide. Shock, 2009, 32(3): 325-331.
19.	張波, 盧兆桐, 袁耒, 等. 家兔輕中度肺爆震傷相關指標及早期主要死亡原因的研究. 創傷外科雜志, 2012, 14(6): 535-538.
20.	郭松文, 朱哲, 孫嘉, 等. 地塞米松對大鼠內毒素急性肺損傷肺泡灌洗液中白細胞介素-1β 和腫瘤壞死因子-α 含量的影響. 中華損傷與修復雜志 (電子版), 2013, 8(5): 11-15.
21.	賀盟, 董利民, 侯曉彬. 兔胸部爆炸傷后 IL-6、IL-8 及 TNF-α 的時間相關性表達. 法醫學雜志, 2014, (2): 85-87.
22.	林瑞云, 林建浜, 戴建偉. 肝素聯合山莨菪堿治療急性肺損傷/急性呼吸窘迫綜合征的臨床觀察. 廣東醫學院學報, 2016, 34(4): 414-419.
23.	曹金鐘, 王靜, 姚麗花, 等. 大劑量氨溴索對肺保護作用的國內研究進展. 臨床肺科雜志, 2014, 19(11): 2060-2063.
24.	Kanie S, Yokohira M, Yamakawa K, et al. Suppressive effects of the expectorant drug ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats. J Toxicol Pathol, 2017, 30(2): 153-159.
25.	楊波, 張東衛, 李小飛, 等. 大劑量氨溴索對大鼠缺血再灌注損傷后的肺保護機制. 西安交通大學學報 (醫學版), 2016, 37(3): 367-371.
26.	林光建. 大劑量鹽酸氨溴索治療急性肺損傷的效果研究. 當代醫學論叢, 2017, 15(15): 33-34.
27.	Yu NB. Therapeutic experience of the application of anisodamine on acute lung injury. J Acute Dis, 2016, 5(5): 382-385.
28.	郭振輝, 洪新, 毛寶齡, 等. 山莨菪堿對 LPS 誘導的急性肺損傷大鼠肺組織 TNF-α、IL-8 表達的影響. 第三軍醫大學學報, 2000, 22(5): 410-413.

1. Ritenour AE, Baskin TW. Primary blast injury: update on diagnosis and treatment. Crit Care Med, 2008, 36(7 Suppl): S311-S317.
2. Smith JE. The epidemiology of blast lung injury during recent military conflicts: a retrospective database review of cases presenting to deployed military hospitals, 2003-2009. Philos Trans R Soc Lond B Biol Sci, 2011, 366(1562): 291-294.
3. Avidan V, Hersch M, Armon Y, et al. Blast lung injury: clinical manifestations treatment and outcome. Am J Surg, 2005, 190(6): 927-931.
4. Chavko M, Prusaczyk WK, McCarron RM. Lung injury and recovery after exposure to blast overpressure. J Trauma, 2006, 61(4): 933-942.
5. Yelveton JT. Pathology scoring system for blast injuries. J Trauma, 1996, 40(3 Suppl): S111-S115.
6. Kirkman E, Watts S, Cooper G. Blast injury research models. Philos Trans R Soc Lond B Biol Sci, 2011, 366(1562): 144-159.
7. Smith JE. Blast lung injury. J R Nav Med Serv, 2011, 97(3): 99-105.
8. 徐立, 金海. 大鼠肺爆震傷模型的建立與傷情分析. 海軍醫學雜志, 2016, 37(1): 9-26.
9. 范崇熙, 張志培, 程慶書, 等. 胸部爆震傷致兔急性呼吸窘迫綜合征模型的建立及相關因素分析. 中國危重病急救醫學雜志, 2011, 23(4): 243-246.
10. 吳山, 孫明, 郭金東, 等. 大鼠肺爆震傷模型的建立和病理變化觀察. 黑龍江醫藥科學, 2001, 24(1): 28-29.
11. 楊衛忠. 肺爆震傷大鼠肺泡上皮細胞通透性改變與 Claudin4 蛋白的表達研究［D］. 山西醫科大學, 2014.
12. 侯曉彬, 李廷慧, 金文波, 等. 地塞米松和山莨菪堿在胸部爆炸傷致急性肺損傷中的防治作用. 中國急救醫學, 2008, 28(6): 531-535.
13. 王靜, 秦霞, 孟偉正. 模擬礦坑瓦斯爆炸致肺部損傷動物實驗模型的建立. 中華實驗外科雜志, 2016, 33(8): 1965.
14. 付澤軍, 李強. 大鼠肺爆震傷簡易模型建立研究. 山西醫科大學學報, 2015, 46(5): 497-498.
15. 付澤軍, 劉龍, 楊衛忠, 等. 緊密連接蛋白 claudin1、3、4 與肺爆震傷致大鼠肺水腫的關系研究. 醫學研究雜志, 2015, 44(11): 31-34.
16. 潘建光, 賴國祥, 文文, 等. 利用簡易三通管路建立大鼠肺爆震傷模型的實驗方法. 醫學研究所學報, 2018, 31(4): 412-415.
17. 雷晉, 段鵬, 郝振明, 等. 成批爆炸燒沖復合傷的救治. 中華損傷與修復雜志 (電子版), 2015, 10(3): 33-36.
18. Chavko M, Adeeb S, Ahlers ST, et al. Attenuation of pulmonary inflammation after exposure to blast overpressure by N-acetylcysteine amide. Shock, 2009, 32(3): 325-331.
19. 張波, 盧兆桐, 袁耒, 等. 家兔輕中度肺爆震傷相關指標及早期主要死亡原因的研究. 創傷外科雜志, 2012, 14(6): 535-538.
20. 郭松文, 朱哲, 孫嘉, 等. 地塞米松對大鼠內毒素急性肺損傷肺泡灌洗液中白細胞介素-1β 和腫瘤壞死因子-α 含量的影響. 中華損傷與修復雜志 (電子版), 2013, 8(5): 11-15.
21. 賀盟, 董利民, 侯曉彬. 兔胸部爆炸傷后 IL-6、IL-8 及 TNF-α 的時間相關性表達. 法醫學雜志, 2014, (2): 85-87.
22. 林瑞云, 林建浜, 戴建偉. 肝素聯合山莨菪堿治療急性肺損傷/急性呼吸窘迫綜合征的臨床觀察. 廣東醫學院學報, 2016, 34(4): 414-419.
23. 曹金鐘, 王靜, 姚麗花, 等. 大劑量氨溴索對肺保護作用的國內研究進展. 臨床肺科雜志, 2014, 19(11): 2060-2063.
24. Kanie S, Yokohira M, Yamakawa K, et al. Suppressive effects of the expectorant drug ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats. J Toxicol Pathol, 2017, 30(2): 153-159.
25. 楊波, 張東衛, 李小飛, 等. 大劑量氨溴索對大鼠缺血再灌注損傷后的肺保護機制. 西安交通大學學報 (醫學版), 2016, 37(3): 367-371.
26. 林光建. 大劑量鹽酸氨溴索治療急性肺損傷的效果研究. 當代醫學論叢, 2017, 15(15): 33-34.
27. Yu NB. Therapeutic experience of the application of anisodamine on acute lung injury. J Acute Dis, 2016, 5(5): 382-385.
28. 郭振輝, 洪新, 毛寶齡, 等. 山莨菪堿對 LPS 誘導的急性肺損傷大鼠肺組織 TNF-α、IL-8 表達的影響. 第三軍醫大學學報, 2000, 22(5): 410-413.

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Experimental observation of cluster therapeutic regimen in early stage of blast-induced acute lung injury in rats

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