The Relationship of Aquaporin-4 Expression and Brain Edema in Cirrhotic Rats with Hepatic Encephalopathy
|School||China Medical University|
|Keywords||AQP-4 Brain edema Blood ammonia Blood-brain barrier cirrhosis|
ObjectiveCerebral edema, a kind of severe complication of various craniocerebral diseases, can lead to death. Nowadays, the strategies are so limited that we can only use osmotic diuretics to dehydrate or decompression by surgery, and there’s no therapy aimed directly at the mechanism of cerebral edema. Lately, the study of aquaporin(AQP) shows that the AQP is an important way for the water transportation. It maybe participate in many kinds of cerebral edema in different diseases. The AQP is a tunnel protein, it can transport free water quickly through the biomembrane. It is the main channel for water to enter or leave cell. There are three kinds of AQPS in the brain, the AQP1,AQP4 and AQP9, among them AQP4 is most important. We now have many documents to confirm that the AQP4 participates in the formation of cerebral edema in the cerebral injury, infarction, hemorrhage and water intoxication. There are some studies that the cerebral edema occurs accompanied with hepatic encephalopathy, especially in patients with liver cirrhosis, but we still have no evidence in the expression and effects of APQ4 during that process.In this experimentation, first we made liver cirrhosis model by injecting carbon tetrachloride into the abdominal cavity, then ammonia was given in cirrhosis group and normal ammonia burden group after making successful model. EB was given from the tail vein. Blood ammonia level was measured. The water content, EB content of brain section was measured respectively, and the expression of AQP4 measured by immuohistochemistry(ISH). All these data was analyzed by statistic software. So we think that it may educe a new pathway for management of hepatic encephalopathy. MethodsAltogether 60 healthy Sprgue-Dawley(SD) rats were divided into four groups at random:(normal group, normal ammonia burden group, cirrhosis group, cirrhosis ammonia burden group). After making models successfully, the arterial plasma ammonia was measured by dry style biochemical method, and the EB content was examined by ratio color method, and the brain water content(BWC)was measured by means of wet to dry and the APQ4 in the brain tissue was assessed by immunohisto-chemistry as well as using the instrument chemiimager to get the gray scale number and positive area of AQP4. Analysis of variance was applied and P＜0.05 was considered statiscally significant.ResultsThe arterial plasma ammonia level, the EB content and the brain water content in cirrhosis ammonia burden group were higher than those of normal group(P<0.05). While the EB content and the brain water content in cirrhosis group were not different compared to normal group(P>0.05)ConclusionThere was obviously brain edema which may be aggravated by increased arterial plasma ammonia in cirrhotic rats with hepatic encephalopathy. The permeability of blood-brain barrier in cirrhotic rats with hepatic encephalopathy was increased. Aquaporin-4 expression was up-regulated in cirrhotic rats with hepatic encephalopathy which suggested that aquaporin-4 may have some function in brain edema formation of cirrhotic rats with hepatic encephalopathy.