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《Chongqing Medicine》 2016-03
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Protective effect of imatinib on myocardial fibrosis in uremic rats

Ma Xin;Wang Li;Gou Fangfang;Shen Hongchun;Cao Ling;Fan Junming;Department of Nephrology,Affiliated Hospital of Luzhou Medical College;Laboratory of Organ Fibrosis Prophylaxis and Treatment by Combine Traditional Chinese and Western Medicine,Research Center of Combine Traditional Chinese and Western Medicine,the Affiliated TCM Hospital,Luzhou Medical College;College of Traditional Chinese Medicine,Luzhou Medical College;State Key Laboratory of Biotherapy,Sichuan University West China Hospital;  
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,5/6group and5/6+I group.All The rats in 5/6group underwent the 5/6nephrectomy and the rats in 5/6+I group were given imatinib by gavage after the operation of 5/6nephrectomy.Hearts were harvested for HE and Sirius red staining at 8weeks post surgery.The expression of PDGFRαwas assessed with immunohistological staining.The real-time PCR was employed to detect the PDGFRαmRNA level in hear samples.Results The urine protein,Scr,BUN of the 5/6group and 5/6+I group were higher than that of Sham group(P0.01).The myocardial pathological score in Sham group was significantly lower than that of 5/6group(P0.01),and the score in 5/6+I group was significantly lower than that of 5/6group(P0.01).The collagen volume fraction(CVF)in 5/6group was significantly higher than that in Sham group(P0.01).And the CVF in 5/6+I group was higher than that in Sham group(P0.05),but lower than that of 5/6group(P0.05).The expression ratio of PDGFRαmRNA and staining rate in 5/6group and 5/6+I group were both much higher than that in Sham group(P0.01),and the expression in 5/6+I group was significantly lower than that in 5/6group(P0.05).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.
【Fund】: 国家自然科学基金项目(81170667);; 四川省科技厅项目(2011JTD0014、2013CDLZ-S20、14JC01503-LH48);; 泸州市科技厅项目[2015-R-55(8/16)]
【CateGory Index】: R542.2;R692.5
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【Secondary Citations】
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