Protective effect of imatinib on myocardial fibrosis in uremic rats / 重庆医学

ABSTRACT

Objective To evaluate the effect of imatinib in improving myocardial fibrosis in uremic rats through regulating the expression of PDGFRα.Methods Seventy two rats were divided into three groups ,which were Sham group ,5/6 group and 5/6+I group .All The rats in 5/6 group underwent the 5/6 nephrectomy and the rats in 5/6+I group were given imatinib by ga‐vage after the operation of 5/6 nephrectomy .Hearts were harvested for HE and Sirius red staining at 8 weeks post surgery .The ex‐pression of PDGFRαwas assessed with immunohistological staining .The real‐time PCR was employed to detect the PDGFRαmR‐NA level in hear samples .Results The urine protein ,Scr ,BUN of the 5/6 group and 5/6+I group were higher than that of Sham group(P<0 .01) .The myocardial pathological score in Sham group was significantly lower than that of 5/6 group (P<0 .01) ,and the score in 5/6+I group was significantly lower than that of 5/6 group (P<0 .01) .The collagen volume fraction (CVF) in 5/6 group was significantly higher than that in Sham group (P<0 .01) .And the CVF in 5/6+ I group was higher than that in Sham group (P<0 .05) ,but lower than that of 5/6 group (P<0 .05) .The expression ratio of PDGFRαmRNA and staining rate in 5/6 group and 5/6+I group were both much higher than that in Sham group (P<0 .01) ,and the expression in 5/6+I group was signif‐icantly lower than that in 5/6 group (P<0 .05) .Conclusion These data suggest that the tyrosine kinase inhibitor imatinib reduces heart injury and attenuates myocardial fibrosis in uremic rat by mechanisms associated with the inhibition of the expression of PDGFRα.