A correlative study between the expression of aquaporin-4 and molecular mechanism of MR diffusion weighted imaging after the hepatic failure in rats

Abstract

Objective To investigate the rule of the cerebral tissues aquaporin-4(AQP-4) expression in acute and chronic hepatic failure mice.To study the molecular biologic mechanism of the diffusion weighted imaging(DWI).Methods Sixty five male Sprague-Dawley rats were divided into 3 groups randomly,including acute(n=25),chronic hepatic failure(n=25)and control group(n=15). Thioacetamide(TAA)intraperitoneal injection produces the acute and chronic hepatic failure models.All rats in groups were examined with MR DWI.We Observed the distribution of abnormal signal on DWI.The DWI single values of top and lateral cortex of parietal lobe,peripheral region of lateral ventricle in the highest hyperintensity section of brain were measured.Blood ammonia values were examined.The pathologic and immuno-histochemistry and RT-PCR examination for brain specimen were performed.All date were analyzed with statistical methods.Results The mean values of blood ammonia were significantly different (P0.01)among control group[(148±32)μmol/L],acute group[(516±46)μmol/L],and chronic group[(158±26)μmol/L].The mean values of MR DWI signal intensity for 3 region of interest(ROIs) were(516±160),(727±183),(656±181)in control group,(1766±438),(1223±503),(1216± 446)in acute group,(700±213),(820±263),(713±243)in chronic group,respectively.There were significant difference among groups,respectively(P0.05).The mean values of expression level of AQP-4 protein were(7 379±1617),(8 104±2 093),(4851±2178)in control group,(9580±2616), (11057±2334),(2949±1735)in acute group,(12137±2332),(11135±3102),(7688±2 925)in chronic group,respectively.There were significant difference among groups,respectively(P 0.05).The expression level of AQP-4 protein in acute group correlated with DWI signal intensity(r= 0.756,P0.05),but no correlations were found between the expression level of AQP-4 protein in chronic group and DWI signal intensity(r=0.236,P0.05).Conclusions Increase of the blood ammonia was the main cause for the brain energy metabolic abnormality and AQP-4 mRNA and protein expression.The hyperammonemia was the key factor in the occurrence and development of the hepatic brain edema.The abnormal findings in DWI signal could reflect the range and degree of the brain edema and AQP-4 protein expression.