Study on functional damage mechanism of the hepatocellular mitochondria in the rats with sepsis

Abstract

Objective To study the effect on the expression of the aquaporin 8 (AQP8) in inner mitochondrial membrane of the liver cells in the rats with sepsis, and on the function of the liver cells and mitochondria. Methods 24 SD rats were divided into the control group and the septic group with 12 rats respectively. The sepsis model of the rats was established by the cecal ligation and puncture. After 18 h of moulding, killing the rats and taking the blood, the alanime aminotransferase (ALT), aspartate aminotransferase (AST) and mitochondrial aspartate aminotransferase (m-AST) were detected. The content of Adenosine Triphosphate (ATP) in the liver cells, mitochondrial membrane potential levels, and the activity of the mitochondrial membrane Na+ -K+ -ATPase, Mg2+ -ATPase, Ca2+ -ATPase and Ca2+ -Mg2+ -ATPase were tested. The expression quantity of AQP8 and AQP8 mRNA were measured with Western blotting and Real-time quantitative polymerase chain reaction (Real-time PCR). Results Compared with the control group, the serum ALT, AST and m-AST was higher that in the septic group and the content of ATP in the liver cells was lower significantly [(233.02±110.16) U/L vs. (29.81±13.16) U/L, (742.56±441.41) U/L vs. (99.78±41.67) U/L, (412.78±252.56) U/L vs. (46.23±24.24) U/L, (19.27±8.76) nmol/mg vs. (94.65±17.79) nmol/mg, P<0.01), the activity of the ATPases of the mitochondria and the mitochondrial membrane potential level was decreased significantly [(2.81±0.81) U/mgprot vs. (4.74±0.84) U/mgprot, (2.59±1.03) U/mgprot vs. (4.49±0.73) U/mgprot, (1.63±1.26) U/mgprot vs. (3.48±0.43) U/mgprot, (2.54±0.97) U/mgprot vs. (4.68±0.81) U/mgprot, 1.73±1.06 vs 7.65±3.54, P<0.01], the expression quantity of AQP8 and the transcription quantity of AQP8 mRNA were reduced (0.68±0.03 vs. 1.24±0.05, 0.34±0.19 vs. 1.00, P<0.01). Conclusion The reduction of the expression quantity of AQP8 in hepatocellular mitochondrial membrane and dysfunction of the ionic channel in sepsis, result in the significant reduction of the mitochondrial membrane potential level and content of ATP in the liver cell, and acute damage to the liver cells finally. Key words: Sepsis; Liver; Mitochondrial; Aquaporin 8