Published online Aug 7, 2018. doi: 10.3748/wjg.v24.i29.3273
Peer-review started: May 4, 2018
First decision: June 6, 2018
Revised: June 19, 2018
Accepted: June 27, 2018
Article in press: June 27, 2018
Published online: August 7, 2018
Hepatorenal syndrome (HRS) is one of the common and severe complications of liver failure and advanced liver disease, with approximately 55% of these patients developing this severe complication. At present, HRS has unclear pathogenesis, limited treatment options, and poor therapeutic efficacy. Once renal dysfunction aggravates rapidly, 60%-80% of patients with HRS will die. Therefore, elucidating the mechanism underlying the development and progression of HRS and taking effective preventive and therapeutic measures may improve the success rate of rescue, the incidence rate, and the mortality rate of HRS.
To detect the protein and mRNA expression of type I inositol 1,4,5-trisphosphate receptor (IP3RI) in the kidney of rats with HRS by Western blot and real-time PCR.
To explore whether high expression of renal IP3RI is associated with Ca2+ influx in vascular smooth muscle cells of glomerular afferent arteries and glomerular mesangial cells in rats with HRS.
D-galactosamine (D-GalN) and/or lipopolysaccharide (LPS) were used to treat male Sprague-Dawley (SD) rats via the tail vein. Twelve hours after injection, massive hepatocyte necrosis with severe hemorrhage occurred in the liver, while renal tissue had a normal morphology. In addition, liver and kidney function was impaired severely, and serum biochemical indexes exhibited significant changes. These changes were consistent with the clinical features of HRS. Western blot and real-time PCR were then used to detect the protein and mRNA expression of renal IP3RI, respectively.
IP3RI protein expression was significantly elevated in rats with HRS. The elevation began at 3 h and reached the peak at 12 h. IP3RI mRNA expression was also significantly elevated in rats with HRS. The elevation began at 3 h and peaked at 9 h.
Joint D-GalN/LPS administration can induce HRS in SD rats at 12 h, which is concomitant with peaked IP3RI protein and mRNA expression in the kidney. Increased expression of IP3RI may be closely associated with HRS development and progression.
Our results suggest that IP3RI may be a signal molecule involved in the reduction of renal blood flow induced by renal vasoconstriction in HRS, thus providing a theoretical basis for further research of the pathogenesis of HRS. Gene silencing technology may be adopted to further elucidate the role of IP3RI in the pathogenesis of HRS.