Swapna I, Kumar K V Sathya Sai, Reddy P Vijaya Bhaskar, Murthy Ch R K, Reddanna P, Senthilkumaran B
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
Neurochem Int. 2006 Aug;49(3):238-44. doi: 10.1016/j.neuint.2006.01.012. Epub 2006 Mar 7.
Fulminant hepatic failure is often associated with a wide range of neurological symptoms which are collectively referred to as hepatic encephalopathy. Fulminant hepatic failure with associated hepatic encephalopathy has a poor prognosis with the currently available sure treatment being only liver transplantation. This is largely owing to the lack of understanding of critical factors involved in the etiology of the condition. Lipid changes have been implicated in cerebral derangements characteristic of hepatic encephalopathy. About 79% of the brain lipid is concentrated in the myelin fraction where they play an important role in ion balance and conduction of nerve impulses. Hence, in the present study we aimed to investigate changes in myelin lipid composition and structure. Myelin was isolated by sucrose density gradient centrifugation from cerebral cortex of male Wistar rats (250-300 g body weight) treated with 300 mg/kg body weight thioacetamide administered twice at 24h interval to induce hepatic encephalopathy. Significant decrease was observed in the cholesterol and phospholipids content of myelin from treated rats. Sphingomyelin, phosphatidylserine and phosphatidylethanolamine content also decreased significantly following 18 h of thioacetamide administration. However, phosphatidylcholine levels remained unaltered. Transmission electron microscopic observation of myelin membrane from cerebral cortex sections showed considerable disorganization in myelin structure. Increase in malondialdehyde levels precede lipid changes leading to the speculation that oxidative damage may be the critical factor leading to decrease in the anionic phospholipids. Changes in myelin were evident only in later stages of hepatic encephalopathy indicating that myelin alteration may not play a role in early stages of hepatic encephalopathy. Nevertheless, myelin alteration may have a crucial role to play in various psycho-motor alterations during later stages of hepatic encephalopathy.
暴发性肝衰竭常伴有多种神经症状，这些症状统称为肝性脑病。伴有肝性脑病的暴发性肝衰竭预后较差，目前唯一有效的治疗方法是肝移植。这主要是由于对该病症病因中关键因素缺乏了解。脂质变化与肝性脑病特有的脑功能紊乱有关。约79%的脑脂质集中在髓鞘部分，它们在离子平衡和神经冲动传导中起重要作用。因此，在本研究中，我们旨在研究髓鞘脂质组成和结构的变化。通过蔗糖密度梯度离心法从雄性Wistar大鼠（体重250 - 300 g）的大脑皮层中分离髓鞘，这些大鼠以300 mg/kg体重的硫代乙酰胺，每隔24小时给药两次以诱导肝性脑病。观察到经处理大鼠的髓鞘中胆固醇和磷脂含量显著降低。硫代乙酰胺给药18小时后，鞘磷脂、磷脂丝氨酸和磷脂酰乙醇胺含量也显著下降。然而，磷脂酰胆碱水平保持不变。对大脑皮层切片的髓鞘膜进行透射电子显微镜观察显示，髓鞘结构出现相当程度的紊乱。丙二醛水平升高先于脂质变化，这导致推测氧化损伤可能是导致阴离子磷脂减少的关键因素。髓鞘变化仅在肝性脑病后期明显，这表明髓鞘改变可能在肝性脑病早期不起作用。然而，髓鞘改变可能在肝性脑病后期的各种精神运动改变中起关键作用。
