Paper - WANFANG MED ONLINE

You Position: Home > Paper

Relationship between aquaporin-4 expression and brain edema in cirrhotic rats with hepatic encephalopathy

( views:209, downloads:7 )

Author:: No author available

Journal Title:: WORLD CHINESE JOURNAL OF DIGESTOLOGY

Issue:: 23

DOI:: 10.3969/j.issn.1009-3079.2008.23.006

Key Word:: 水通道蛋白4;脑水肿;血氨;血脑屏障;肝硬化;免疫组化

Abstract：目的:探讨肝硬化肝性脑病脑水肿的发生机制,为治疗脑水肿新方法的发现提供理论依据.方法:实验大鼠随机分为正常组(n=10)、正常氨负荷组(n=10)、肝硬化组(n=20)和肝硬化氨负荷组(n=20).后2组给予400 g/L CCl4橄榄油,按0.2 mL/kg腹腔注射.2次/wk,共12wk.前两组给与橄榄油.注射剂量、部位、频次、时间同后两组.正常氨负荷组、肝硬化氨负荷组分别在最后1次给药2d后,给与乙酸胺盲肠注射.4组大鼠通过尾静脉注射伊文恩蓝(EB)应用干式生化法测量动脉血氨,比色法测量EB含量,干-湿重法测量脑含水量,免疫组化法染色并通过图像分析系统分析脑组织中AQP4的表达.结果:肝硬化组动脉血氨与正常组、正常氨负荷组比较有差异性(97.20±29.66 μmol/Lvs 42.62±10.11,59.33±15.06 μmol/L,均P＜0.05),肝硬化氨负荷组的动脉血氨(420.18±75.91 μmol/L)与其他各组比较有明显的差异性(P＜0.01).肝硬化组EB和脑含水量与正常组、正常氨负荷组比较没有差异性.而肝硬化氨负荷组与其他各组比较有差异性(1.96±0.55 μg/g vs 1.41±0.46,1.19±0.38,1.05±0.18 μg/g;75.14±5.68 vs 65.58±4.14,62.14±2.29,66.27±4.57,均P＜0.05).肝硬化大鼠AQP4表达部位与正常大鼠一致,但肝硬化大鼠给与氨负荷后,无论是平均吸光度还是显色阳性面积均较正常组增高(P＜0.05).结论:AQP4可能在肝硬化肝性脑病大鼠脑水肿形成中起一定的作用.

Reference

[1]Olivier Detry,Arnaud De Roover,Pierre Honoré,etc.Brain edema and intracranial hypertension in fulminant hepatic failure: Pathophysiology and management[J].2006,(46).
[2]吕飒,宋红丽,王静艳,等.急性肝坏死小鼠血脑屏障通透性的改变[J].2004,(6).
[3]M C, Papadopoulos,S, Saadoun,D K, Binder,etc.Molecular mechanisms of brain tumor edema.[J].2004,129(4).
[4]Asai K,Sobue K,Umenishi F,etc.Hyperosmolar mannitol simulates expression of aquaporins 4 and 9 through a p38 mitogen-activated protein kinase-dependent pathway in rat astrocytes.[J].2003,278(45).
[5]Hudson CS,Agre P,Rash JE,etc.Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord.[J].1998,95(20).
[6]Zwingmann C.The anaplerotic flux and ammonia detoxification in hepatic encephalopathy.[J].2007,22(3).
[7]Bollen AW,Chan P,Verkman AS,etc.Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.[J].2000,6(2).
[8]F, Miese,G, Kircheis,H J, Wittsack,etc.1H-MR spectroscopy, magnetization transfer, and diffusion-weighted imaging in alcoholic and nonalcoholic patients with cirrhosis with hepatic encephalopathy.[J].2006,27(5).
[9]Chen M,Rama Rao KV,Simard JM,etc.Suppression of ammonia-induced astrocyte swelling by cyclosporin A.[J].2003,74(6).
[10]Vargas V,Margarit C,Kulisewsky J,etc.The development of low-grade cerebral edema in cirrhosis is supported by the evolution of (1)H-magnetic resonance abnormalities after liver transplantation.[J].2001,35(5).
[11]Papadopoulos MC,Verkman AS.Aquaporin-4 gene disruption in mice reduces brain swelling and mortality in pneumococcal meningitis[J].2005,280(14).
[12]M D, Lee,L S, King,P, Agre.The aquaporin family of water channel proteins in clinical medicine.[J].1997,76.
[13]Norenberg MD,Jayakumar AR,Panickar KS,etc.Oxidative stress and mitogen-activated protein kinase phosphorylation mediate ammonia-induced cell swelling and glutamate uptake inhibition in cultured astrocytes.[J].2006,26(18).
[14]A, Rovira,E, Grivé,S, Pedraza,etc.Magnetization transfer ratio values and proton MR spectroscopy of normal-appearing cerebral white matter in patients with liver cirrhosis.[J].1900,22(6).
[15]Badaut J,Regli L,Lasbennes F,etc.Aquaporins in brain: distribution, physiology, and pathophysiology.[J].2002,22(4).
[16]Carpenedo R,Bergqvist PB,Apelqvist G,etc.Plasma and brain levels of oxindole in experimental chronic hepatic encephalopathy: effects of systemic ammonium acetate and L-tryptophan.[J].1999,85(3).
[17]Jalan R,Wright G.Management of hepatic encephalopathy in patients with cirrhosis.[J].2007,21(1).
[18]Panickar KS,Norenberg MD,Jayakumar AR,etc.Ammonia induces the mitochondrial permeability transition in primary cultures of rat astrocytes.[J].2001,66(5).
[19]Norenberg MD,Rama-Rao KV.Aquaporin-4 in hepatic encephalopathy.[J].2007,22(3).
[20]Clemmesen O,Ott P,Larsen FS.Cerebral metabolic disturbances in the brain during acute liver failure: from hyperammonemia to energy failure and proteolysis.[J].2005,47(1).
[21]Beyer TF,Unterberg AW,Stover JF.Riluzole reduces brain swelling and contusion volume in rats following controlled cortical impact injury.[J].2000,17(12).