A Correlative Study Between The Expression Of Aquaporin-4 And Molecular Mechanism Of MR DWI After The Hepatic Failure In Rats

Objective: To investigate the rule of the aquaporin-4 (AQP-4) expression in the acute and chronic hepatic failure mice cerebral tissues. To study the molecular biologic mechanism of the diffusion weighted imaging (DWI); provide experimental evidences for clinical imaging diagnosis and treatment. Methods: 25 male Sprague-Dawley rats were divided into 3 groups randomly, including acute group (n=25) chronic group (n=25) and control group (n=15). Using the thioacetamide (TAA) peritoneo-injection to produce the acute and chronic hepatic failure models, the control group using the physiologic saline for substitute. Evaluating the hepatic encephalopathy (HE) symptoms of acute group in 4th day and chronic group in 15th weeks by same grades, all rats in groups were examined with MR DWI. Observing the distribution of abnormal signal, the DWI and ADC value of parietal lobe, lateral lobe, peripheral region of lateral ventricle in the highest hyperintensity single signal section of brain were measured. After that, the animals were sacrificed and blood ammonia values were measured, the pathologic and immuno- histochemistry and reverse transcription -PCR examination were performed. The AQP-4 and glial fibrillary acidic protein (GFAP) expression were measured with the Image Analysis. All date were analyzed with statistical methods. Results: There was no significant change of the DWI and no symptom of HE and no brain edema in control group, the AQP-4 and GFAP expression did not changed obviously; In the acute group blood ammonia increased by 3.5 times more than controlgroup with moderate-severe HE symptom, abnormal high signal intensity was found in brain cortex and peripheral region of lateral ventricle, the DWI value increased and ADC value decreased with correlation with the level of blood ammonia and AQP-4 mRNA or protein expressions, while the astrocyte and endothelia edema had been found by pathologic examination. In chronic group the blood ammonia level did not increase definitely and the HE symptom was mild-moderate grade. There was slightly high signal intensity in the same areas as acute group, but the DWI and ADC value had not changed obviously as acute group, lightly brain edema and astrocyte hyperplasia had been observed, the AQP-4 mRNA and AQP-4 GFAP protein expression increased obviously. Conclusion: 1. Increase of the blood ammonia was the main cause for the brain energy metabolic abnormality and AQP-4 mRNA and protein expression, hyperammonemia was the key occurrence and development of the hepatic brain edema. 2. MR DWI was a highly sensitive imaging modality for the hepatic brain edema diagnosis, the abnormal findings in DWI signal could reflect the range and degree of the brain edema and AQP-4 protein expression. 3. In the acute hepatic failure with moderate-severe HE, MR DWI could early find the appearances of brain edema by the increase of DWI value and decrease of ADC value, which also show the increase of AQP-4 protein expression indirectly. 4. There were slight brain edema and astrocyte hyperplasia in chronic hepatic failure, the expression of AQP-4 mRNA and AQP-4 protein had increased. The signal changes in brain cortex and peripheral region of lateral ventricle could be found on MR DWI in this group, but the differences between the normal and abnormal were not obviously.