Li Jun-Jie, Ji Ru, Shi Yong-Quan, Wang Ya-Yun, Yang Yan-Ling, Dou Ke-Feng
Department of Anatomy and K.K. Leung Brain Research Centre, Fourth Military Medical University; ; Departments of Hepatobiliary Surgery and.
Exp Ther Med. 2012 Dec;4(6):1075-1080. doi: 10.3892/etm.2012.721. Epub 2012 Sep 24.
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.
肝性脑病（HE）是一种常伴随肝硬化出现的神经精神异常疾病，通常难以治疗和管理。氯离子稳态的改变与多种脑部疾病的发生有关。在本研究中，我们探讨了氯离子稳态是否与肝性脑病相关。采用实时逆转录聚合酶链反应（RT-PCR）检测了29例I-II级肝性脑病肝硬化患者、36例III-IV级肝性脑病肝硬化患者、20例无肝性脑病的肝硬化患者及15名健康对照者血浆中氯离子排出系统（KCC2）和氯离子摄入系统（NKCC1）的mRNA水平。轻度和重度肝性脑病肝硬化患者KCC2的mRNA水平显著低于无肝性脑病的肝硬化患者及健康对照者。然而，不同组之间NKCC1的mRNA水平无差异。此外，对于肝性脑病肝硬化患者，KCC2水平与血氨水平及肝功能评分（Child-Pugh评分和终末期肝病模型评分）之间存在显著负相关；KCC2水平与神经状态（格拉斯哥评分）之间也存在显著正相关。总之，我们的研究表明，KCC2和NKCC1失衡可能是检测肝性脑病及监测疾病进展的一种新型生物标志物。
