[Renal type I inositol 1,4,5-triphosphate receptors expression increases in fulminant hepatic failure in mice]

To study the changes of expression of type I inositol 1,4,5 triphosphate receptors (IP3RI) in the kidneys of mice with fulminant hepatic failure (FHF) in order to understand the role renal vasoconstriction plays in the development of hepatorenal syndrome (HRS).

One hundred twenty male Balb/c mice were divided into 4 groups. In the fourth group (60 mice) lipopolysaccharide with D-galactosamine was injected intraperitoneally to induce acute liver necrosis. The first-third groups (20 mice in each group) served as controls and those mice were given NS, LPS or GalN intraperitoneally. At the end of 2 h, 6 h, and 9 h, mice were sacrificed and their livers and kidneys were removed and examined histologically. Immunohistochemistry, Western blot and reverse transcription PCR (RT-PCR) were used to detect the distribution and expression of IP3RI in the kidneys.

IP3RI protein was localized in the cytoplasma of glomerular mesangial cells and vascular smooth muscle cells in the kidneys. In the kidney tissues from mice with FHF at 6 h and 9 h, IP3RI-positive staining cells increased significantly (6 h: chi(2)=7.11, P less than 0.01; 9 h: (chi)2=9.15, P less than 0.01). Western blot demonstrated a consistent and significant increase of IP3RI expression in mice with FHF at 6 h and 9 h (6 h: t=3.16, P less than 0.05; 9 h: t=5.43, P less than 0.01). Using RT-PCR we observed that IP3RI mRNA in FHF samples at 2 h, 6 h and 9 h was markedly up-regulated in comparison to that of the controls (2 h: t=2.47, P less than 0.05; 6 h: t=4.42, P less than 0.01; 9 h: t=2.16, P less than 0.05).

The expression of IP3RI protein increased in glomerular mesangial cells and renal vascular smooth muscle cells of FHF mice. Perhaps this was caused by IP3RI mRNA up-regulation.