Therapeutic Effect of Angiotensin-converting Enzyme 2 on Lipopolysaccharide-induced Acute Lung Injury in Rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZouYuekun ¹ ,  LiYi ¹ , XueQing ² , JiangFuqiang ¹ , ZhangQi ¹ , LiYanbo ¹ , ZhangChunyan ¹ , LiuYuhong ¹

1. General VIP Department of Navy General Hospital, Beijing, 100048, China;
2. ;

Corresponding author：

LiYi, Email: yuekunzou@hotmail.com

Keywords：

Acute lung injury; Lipopolysaccharide; Angiotensin-converting enzyme 2

DOI：

10.7507/1671-6205.2014122

Video：

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Objective To explore the therapeutic effect of angiotensin-converting enzyme 2 (ACE2) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a rat model. Methods Twenty-four Wistar rats were randomly divided into a control group, an ALI group, and an ACE2 group.The rat ALI model was established by intravenous injection of LPS.Then the rats in the ACE2 group received intraperitoneally injection of recombinant rat ACE2 by 0.1 mg/kg immediately after LPS injection.All rats were sacrificed 2 hours later.Rat arterial blood gas was analyzed and wet/dry (W/D) weight ratio of lung tissue was measured.Concentrations of TNF-α, IL-8 and IL-1βin lung tissue homogenates were measured by ELISA.Pulmonary pathological changes were evaluated by hematoxylin-eosin stain under light microscope. Results ALI induced by LPS was successfully established in the rats.ACE2 pretreatment markedly impoved PaO₂ level of the ALI rats(P < 0.05), and decreased the lung W/D ratio(P < 0.05).The concentration of TNF-α, IL-8 and IL-1βin lung tissue homogenates were also inhibited by ACE2.And the lung histopathological changes and score were attenuated in the ACE2 group. Conclusion ACE2 treatment has therapeutic effects on ALI induced by LPS.

Citation： ZouYuekun, LiYi, XueQing, JiangFuqiang, ZhangQi, LiYanbo, ZhangChunyan, LiuYuhong. Therapeutic Effect of Angiotensin-converting Enzyme 2 on Lipopolysaccharide-induced Acute Lung Injury in Rats. Chinese Journal of Respiratory and Critical Care Medicine, 2014, 13(5): 504-507. doi: 10.7507/1671-6205.2014122 Copy

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12.	施卉, 任成山.急性肺损伤/呼吸窘迫基础及临床研究进展.中华肺部疾病杂志(电子版), 2013, 6:350-355.

1. Blank R, Napolitano LM.Epidemiology of ARDS and ALI.Crit Care Clin, 2011, 27:439-458.
2. Imai Y, Kuba K, Penninger JM.Lessons from SARS:a new potential therapy for acute respiratory distress syndrome (ARDS) with angiotensin converting enzyme 2(ACE2).Masui, 2008, 57:302-310.
3. 沈利汉, 莫红缨, 蔡立华, 等.肾素2血管紧张素系统与ALI/ARDS的关系探讨.中国呼吸与危重监护杂志, 2010, 9:310-314.
4. Mikawa K, Nishina K, Tokao Y, et al.ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits.Anesth Analg, 2003, 97:1751-1755.
5. 陈娇, 钱晓明, 聂时南.急性肺损伤动物模型的研究现状.医学研究生学报, 2013, 26:851-854.
6. Burrell LM, Johnston CI, Tikelis C, et al.ACE2, a new regulator of the renin-angiotensin system.Trends Endocrinol Metab, 2004, 15:166-169.
7. Treml B, Neu N, Kleinsasser A, et al.Recombinant angiotensin-converting enzyme 2 improves pulmonary blood flow and oxygenation in lipopolysaccharide-induced lung injury in piglets.Crit Care Med, 2010, 38:596-601.
8. McCarter SD, Mei SH, Lai PF, et al.Cell-based angiopoietin-1 gene therapy for acute lung injury.Am J Respir Crit Care Med, 2007, 175:1014-1026.
9. Imai Y, Kuba K, Rao S, et al.Angiotensin converting enzyme 2 protects from severe acute lung failure.Nature, 2005, 436:112-116.
10. Shi Y, Zhang B, Chen XJ, et al.Osthole protects lipopolysaccharide-induced acute lung injury in mice by preventing down-regulation of angiotensin-converting enzyme 2.Eur J Pharm Sci, 2013, 48:819-824.
11. Al-Maghrebi M, Benter IF, Diz DI.Endogenous angiotensin-(1-7) reduces cardiac ischemia-induced dysfunction in diabetic hypertensive rats.Pharmacol Res, 2009, 59:263-268.
12. 施卉, 任成山.急性肺损伤/呼吸窘迫基础及临床研究进展.中华肺部疾病杂志(电子版), 2013, 6:350-355.

Chinese Journal of Respiratory and Critical Care Medicine

Therapeutic Effect of Angiotensin-converting Enzyme 2 on Lipopolysaccharide-induced Acute Lung Injury in Rats

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