Influence Of Dexamethasone On AQP₁ Expression In Hepatobiliary System Of Rats With ANIT-induced Cholestasis

Objective:This study was to induce rat models of cholestasis byα-isothiocyanate (ANIT) and dexamethasone treatment was on . Changes of rat liver structure,liver function and the capacity of bile were observed, using immunohistochemical methods to detect the aquaporin1 expression and their expression laws. To study the influence of dexamethasone on hepatocyte function of bile secretion and explore its impact mechanism.Methods:32 healthy adult male Wistar rats were randomly divided into 4 groups. The group treated with only peanut oil is the group A.B group is the group treated with only ANIT eanut oil.C group is the group treated with ANIT eanut oil and injected with dexamethasonea at the same time.D group is the group treated with ANIT eanut oil and injected with dexamethasonea after 24 hours. All rats were killed after 48 hours to collect samples.A single oral dose of 150 mg/kg ANIT dissolved in peanut oil was given to rats by gavage(10g/l) to induce liver injury. Intraperitoneal injection was given with dexamethasone (10 mg/kg) compatibl 2 ml normal saline. The common bile duct of all rats were intubated to collect bile in one hour , portal blood were send to test liver function with automatic biochemical analyzer. Liver specimens stained HE were on light microscopic observation. Immunohistochemical methods detected aquaporin1 expression. Three sections of each rat were image analyzed and the average gray level were determined.Results:1.Bilirubin changes:TBIL, DBIL of Serum from group B are higher than that from A (P<0.01). The bilirubin indicators of group C and D were lower than that of group B (P <0.01)while D is little higher than that of Group C (P >0.05). The direct bilirubin of BCD three groups are main.2. ALP changes: ALP of serology from the B group was significantly higher than that from A group (P <0.01). Group B is higher than C (P <0.05)while B and C is lower than D (P <0.01).3. ALT changes: ALT of serology from the B group was significantly higher than that from A group (P <0.01). The CD groups have no difference (P> 0.05), The BD groups also have no difference (P> 0.05)while B is lower than C. (P <0.01).4. Capacity of bile flow: The A group is obviously more than other B group (P <0.01). In BCD three groups, Group C is more than BD groups (P <0.01)whil Group D is more than group B (P <0.01).5. Pathological changes: The contour and color of the liver from A group is normal. Pathology observation of liver tissue showed that the Hepatic Lobules structure is clear, liver cells cable is neat and orderly, the nucleus large and round , nuclear membrane clear and abundant cytoplasm. B group showed that liver appearance swelled,color was gray. Liver histological observation showed lobular hyperplasia between the bile duct and its epithelial cells swelling and necrosis ,shedding debris, and the bile duct became obstructive.The bile duct hyperplasia, Hepatic Lobules ill-defined contours, many inflammatory cells infiltrated. Liver cells cloudy swelled ,draw acuoles, eosinophilic change necrosis Obviously. The B group was the most serious. The pathological changes of Group D and Group C were slightly reduced.6. Immunohistochemical optical density value of biopsy: There are brown granules in the cytoplasmic membrane of Group A. B group were significantly lessed. The CD have some in the membrane.The value of A group is significantly higher than that of B group (P <0.01). In BCD three groups, group C is higher than group D and B(P <0.01), and Group D moderately higher than that of B (P >0.05).7. Spearman correlation analysis complied with optical density values and the capacity of bile flow, the correlation Coefficient is 0.885 (P <0.01), suggesting that the two variabls are closely related.Coclusion:A single oral administration with ANIT can induce cholestasis successfully. Dexamethasone increased the hepatobiliary AQP1 expression of the ANIT-induced cholestasis.Bile secretion of the intervention group have an increase,the OD value and the BC are closely related.The bilirubin indicators decreased.So the dexamethasone treatment have its role in model rats. We discussed that clinical cases of acute jaundice induced by chemical injury should be early intervented with hormone agents.