Published online Apr 28, 2007. doi: 10.3748/wjg.v13.i16.2344
Revised: March 3, 2006
Accepted: March 8, 2007
Published online: April 28, 2007
AIM: To delineate the mechanisms of renal vasocon-striction in hepatorenal syndrome (HRS), we investigated the expression of typeIinositol 1, 4, 5-triphosphate receptors (IP3RI) of kidney in mice with fulminant hepatic failure (FHF).
METHODS: FHF was induced by lipopolysaccharide (LPS) in D-galactosamine (GalN) sensitized BALB/c mice. There were 20 mice in normal saline (NS)-treated group, 20 mice in LPS-treated group, 20 mice in GalN-treated group, and 60 mice in GalN/LPS-treated group (FHF group). Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3RIin kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription (RT)-PCR.
RESULTS: Kidney tissues were morphologically normal at all time points in all groups. IP3RIproteins were found localized in the plasma region of glomerular mesangial cells (GMC) and vascular smooth muscle cells (VSMC) in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3RIstaining was up-regulated. Results from Western blot demonstrated consistent and significant increment of IP3RIexpression in mice with FHF at 6 h and 9 h (t = 3.16, P < 0.05; t = 5.43, P < 0.01). Furthermore, we evaluated IP3RImRNA expression by RT-PCR and observed marked up-regulation of IP3RImRNA in FHF samples at 2 h, 6 h and 9 h compared to controls (t = 2.97, P < 0.05; t = 4.42, P < 0.01; t = 3.81, P < 0.01).
CONCLUSION: The expression of IP3RIprotein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3RImRNA.