Abstract:

【Abstract】Objective： To investigate whether Rho-kinase inhibition has a therapeutic role on the peritoneal mesothelium EMT in a rat model of peritoneal dialysis. Methodology: A rat model of peritoneal dialysis was induced by a daily intraperitoneal infusion of 4.25% Dianeal. Twenty four SD rats were divided into four groups: N Group is normal control group (n=6), PD Group is peritoneal dialysis group (n=6), Fas 5mg (n=6) and Fas 10mg group (n=6) was daily received respectively intraperitoneal injection of 4.25% Dianeal and 5mg/kg or 10 mg/kg fasudil. Immunofluorescence, Western blot and RT-PCR were used to detect the expression of TGF-β, I, αSMA and E-cadherin in each group. The activity of Rho-kinase was determined by western immunoblotting.  Results: Rho-kinase was activated in the peritoneum of the PD group, which was inhibited by fasudil in a dose-dependent manner. Compared with normal group, the expressions of TGF-β and αSMA in PD group were significantly increased, and the expression of E-cadherin was also markedly decreased. Compared with PD group, the mRNA and protein expressions of TGF-β and αSMA were significantly downregulated in fasudil treatment groups in a dose-dependent manner, while the expression of E-cadherin was markedly upregulated in fasudil treatment groups in a dose-dependent manner. Conclusion: Rho-kinase activation play an important role in peritoneal mesothelium EMT in peritoneal dialysis rats, and the inhibition of Rho-kinase by fasudil can significantly inhibit peritoneal mesothelium EMT and improve peritoneal structure and function.

Key words: Rho-kinase, Peritoneal Dialysis, Fasudil, EMT;