Changes in expression of the chloride homeostasis-regulating genes, KCC2 and NKCC1, in the blood of cirrhotic patients with hepatic encephalopathy.

Changes in expression of the chloride homeostasis-regulating genes, KCC2 and NKCC1, in the blood of cirrhotic patients with hepatic encephalopathy.
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肝硬化肝性脑病患者血液中氯稳态调节基因 KCC2 和 NKCC1 表达的变化

DOI:
10.3892/etm.2012.721
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发表时间:
2012-12
影响因子:
2.7
通讯作者:
Dou KF
Dou KF
中科院分区:
医学4区
文献类型:
--
作者:
Li JJ;Ji R;Shi YQ;Wang YY;Yang YL;Dou KF

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肝性脑病(HE)是一种通常伴随肝硬化的神经精神异常,通常难以治疗和管理。氯化物体内平衡的改变与许多脑部疾病的发生有关。在这项研究中,我们考虑氯离子稳态是否与HE有关。采用实时荧光定量pcr技术检测29例肝硬化ⅰ-ⅱ级HE患者、36例肝硬化ⅲ-ⅳ级HE患者、20例非HE患者和15例健康对照者血浆中Cl -挤压系统(KCC2)和Cl -侵入系统(NKCC1) mRNA水平。与无HE的肝硬化患者或健康对照组相比,轻度和重度HE肝硬化患者的KCC2 mRNA水平显著降低。然而,NKCC1 mRNA水平在不同组之间没有差异。此外,对于肝硬化HE患者,KCC2水平与血氨水平和肝功能评分(Child-Pugh和终末期肝病评分模型)呈显著负相关;KCC2水平与神经系统状态(格拉斯哥评分)之间也存在显著的正相关。总之,我们的研究表明,KCC2和NKCC1的失衡可能是检测HE和监测疾病发展的一种新的生物标志物。
Hepatic encephalopathy (HE), a neuropsychiatric abnormality that commonly accompanies cirrhosis of the liver, is often difficult to treat and manage. Changes in chloride homeostasis are involved in the generation of a number of brain disorders. In this study, we considered whether chloride homeostasis is associated with HE. The mRNA levels of the Cl− extrusion system (KCC2) and the Cl− intrusion system (NKCC1) were detected by real-time RT-PCR in the plasma of 29 cirrhotic patients with HE of grade I-II, 36 cirrhotic patients with HE of grade III–IV, 20 cirrhotic patients without HE and 15 healthy controls. The mRNA levels of KCC2 in cirrhotic patients with mild and severe HE were significantly lower compared to those in cirrhotic patients without HE or in the healthy controls. However, NKCC1 mRNA levels did not differ between the different groups. In addition, for cirrhotic patients with HE, there were significant negative correlations between KCC2 levels and the levels of blood ammonia and hepatic function scores (Child-Pugh and model for end-stage liver disease scores); there was also a significant positive correlation between KCC2 levels and neurological status (Glasgow scores). In conclusion, our study indicates that an imbalance of KCC2 and NKCC1 may be a novel biomarker for detecting HE and for monitoring disease development.
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发表时间: 2012
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