The Role of Intra-abdominal Hypertension on the Expression of Aquaporin 1 and Aquaporin 5 in the Lung of Cirrhotic Mice_West China Medical Journal

Authors：

ZHANG Zhaojie ,  YANG Changqing

Division of Gastroenterology and Institute of Digestive Diseases, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, P.R.China;

Corresponding author：

YANG Changqing, Email: soramd@21cn.com

Keywords：

腹内高压; 肝硬化; 水通道蛋白; 肺水肿; 小鼠

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【摘要】　目的　探讨腹水引起的腹内高压对肝硬化小鼠肺组织水通道蛋白1（AQP1）和水通道蛋白5（AQP5）表达的影响。　方法　雄性美国癌症研究所（Institudo of Cancer Reseach，ICR）小鼠50只，随机取10只作正常对照组（腹压0 cm H2O，1 cm H2O=0.098 kPa），其余40只用四氯化碳建立肝硬化小鼠模型，并随机分为4组:肝硬化（腹压0 cm H2O）组、肝硬化（腹压5 cm H2O）组、肝硬化（腹压10 cm H2O）组、肝硬化（腹压20 cm H2O）组，通过腹腔注射不同量的白蛋白生理盐水形成不同的腹压，并维持腹压24 h后取肺组织行病理、免疫组织化学、肺湿/干比值及实时荧光定量PCR检测AQP1和AQP5 mRNA表达量。　结果　与正常对照小鼠相比，肝硬化小鼠肺AQP5、AQP1表达明显下降（P lt;0.05）；肝硬化小鼠随着腹内压的升高，肺湿/干比值升高，AQP5、AQP1表达相应增加（P lt;0.05）。　结论　肝硬化可以影响肺AQP1、AQP5的表达；肝硬化小鼠随着腹内压的升高，AQP1、AQP5表达相应增加，并与肺水肿的严重程度密切相关。
【Abstract】　Objective　 To investigate the role of intra-abdominal hypertension caused by ascites on the expression of Aquaporin (AQP) 1 and AQP 5 in the lung of cirrhotic mice.　Methods　 We randomly chose 10 from 50 male Institude of Cancer Research (ICR) mice to form the control group [intra-abdominal pressure (IAP)=0 cm H2O, 1 cm H2O=0.098 kPa]. The model of cirrhosis were prepared by subcutaneous injection of carbon tetrachloride for the rest 40 mice which were then randomly divided into 4 groups: cirrhosis (IAP=0 cm H2O) group, cirrhosis (IAP=5 cm H2O) group, cirrhosis (IAP=10 cm H2O) group, and cirrhosis (IAP=20 cm H2O) group. Saline with different volume of albumin was injected into the peritoneum of each mouse in order to form different IAP. After 24 hours, analysis of pathology, immunochemistry and wet/dry ratio was done for the lungs of these mice; and the expression of AQP1 and AQP5 at the protein and mRNA levels were analyzed by IHC and qRT-PCR.　Results　 Compared with the normal mice, the expression of AQP1 and AQP5 in lungs of cirrhotic mice were significantly lower (P lt;0.05). Both the lung wet/dry ratio and the expression of AQP1 and AQP5 raised with the increase of IAP.　Conclusion　 Cirrhosis can affect the expression of AQP1 and AQP5 in lungs. The expression of AQP5 and AQP1 in lungs of cirrhotic mice increases with the increase of IAP, which is also closely correlated with the severity of pulmonary edema.

Citation： ZHANG Zhaojie,YANG Changqing. The Role of Intra-abdominal Hypertension on the Expression of Aquaporin 1 and Aquaporin 5 in the Lung of Cirrhotic Mice. West China Medical Journal, 2011, 26(2): 165-169. doi: Copy

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8.	King LS, Agre P. Pathophysiology of the aquaporin-water channel[J]. Ann Rev Physio, 1996, 58: 619-648.
9.	Towse JE, Harrod KS, Krane CM, et al. Decreased expression of AQP1 and AQP5 in mouse lung after acute viral infection[J]. Am J Respir Cell Mol Bio, 2000, 22(1): 34-44.
10.	Jiao GY, Li ER, Yu RJ. Decreased expression of AQP1 and AQP5 in acute injured lung in rats[J]. Chin Med J, 2002, 115(7): 963-967.
11.	Bai C, Fukuda N, Song Y, et al. Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice[J]. J Clin Invest, 1999, 103(4): 555-561.
12.	高巨, 招伟贤, 肖建斌, 等. “失血性休克-内毒素”二次打击所致肺损伤水通道蛋白的表达[J]. 中国急救医学, 2007, 27(6): 546-549.
13.	谢艳萍, 陈才平, 王建春, 等. 急性肺损伤大鼠肺水通道蛋白1和5表达及功能的实验研究[J]. 中华结核和呼吸杂志, 2005, 28(6): 385-389.
14.	Song Y. Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice[J]. J Physiol, 2000, 15(3): 771-779.
15.	Lai KN, Leung JC, Metz CN, et al. Role for macrophage migration inhibitory factor in acute respiratory distress syndrome[J]. J Patho, 2003, 199(4): 496-508.
16.	Jang AS, Lee JU, Choi IS, et al. Expression of nitric ocide synthase, aquaporin1 and aquaporin5 in rat after bleomycin inhalation[J]. Intensive Care Med, 2004, 30(3): 489-495.

1. 　Agre P, Kozono D. Aquaporin water channels molecular mechanisms for human diseases[J]. FEBS Lett, 2003, 27, 555(1): 72-78.
2. 　Erik J. Teicher, Micheal D. Pasquale, et al. Abdominal compartment syndrome[J]. Operat Tech Gen Surg, 2008, 10(1): 39-59.
3. 　Scheppach W. Abdominal compartment syndrome[J]. Best Pract Res Clin Gastroenterol, 2009, 23(1): 25-33.
4. 　Towse JE, Harrod KS, Krane CM, et al. Decreased expression of AQP1 and AQP5 in mouse lung after acute viral infection[J]. Am J Respir Cell Mol Bio, 2000, 22(1): 34-44.
5. 　Ma T, Fukuda N, Song Y, et al. Lung fluid transport in aquaporin-5 knockout mice[J]. J Clin Invest, 2000, 105 (1): 93-100.
6. 　Jiao G, Li E, Yu R. Decreased expression of AQP1 and AQP5 in acute injured lungs in rats[J]. Chin Med J, 2002, 115(7): 963-967.
7. 　岳冬梅, 薛辛东. 水通道蛋白1, 5与新生鼠高氧肺损伤脑水肿的关系研究[J]. 中国当代儿科杂志, 2006, 2(4): 147-150.
8. 　King LS, Agre P. Pathophysiology of the aquaporin-water channel[J]. Ann Rev Physio, 1996, 58: 619-648.
9. 　Towse JE, Harrod KS, Krane CM, et al. Decreased expression of AQP1 and AQP5 in mouse lung after acute viral infection[J]. Am J Respir Cell Mol Bio, 2000, 22(1): 34-44.
10. 　Jiao GY, Li ER, Yu RJ. Decreased expression of AQP1 and AQP5 in acute injured lung in rats[J]. Chin Med J, 2002, 115(7): 963-967.
11. 　Bai C, Fukuda N, Song Y, et al. Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice[J]. J Clin Invest, 1999, 103(4): 555-561.
12. 　高巨, 招伟贤, 肖建斌, 等. “失血性休克-内毒素”二次打击所致肺损伤水通道蛋白的表达[J]. 中国急救医学, 2007, 27(6): 546-549.
13. 　谢艳萍, 陈才平, 王建春, 等. 急性肺损伤大鼠肺水通道蛋白1和5表达及功能的实验研究[J]. 中华结核和呼吸杂志, 2005, 28(6): 385-389.
14. 　Song Y. Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice[J]. J Physiol, 2000, 15(3): 771-779.
15. 　Lai KN, Leung JC, Metz CN, et al. Role for macrophage migration inhibitory factor in acute respiratory distress syndrome[J]. J Patho, 2003, 199(4): 496-508.
16. 　Jang AS, Lee JU, Choi IS, et al. Expression of nitric ocide synthase, aquaporin1 and aquaporin5 in rat after bleomycin inhalation[J]. Intensive Care Med, 2004, 30(3): 489-495.

West China Medical Journal

The Role of Intra-abdominal Hypertension on the Expression of Aquaporin 1 and Aquaporin 5 in the Lung of Cirrhotic Mice

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