Effects of losartan on renal function and expression of phospho-p38 mitogen-activated protein kinase in early diabetic glomeruli
WANG Li-Hui,DUAN Hui-Jun, SHI Yong-Hong,LIU Qing-Juan,HE Ning,LIU Shu-Xia,GAO Feng (Dept of Pathology,Hebei Medical University,Shijiazhuang 050017,China)
Aim To investigate the effects of Losartan on renal function and structure in experimental diabetic rats, to observe the function of p38 MAPK signal trusduction in this process. Methods Diabetes was induced in uninephrectomized male Wistar rats by intrapetitoneal injection of STZ(65 mg·kg -1) for 4 Weeks. Losartan(40 mg·kg -1) was administered daily by gavage from the next day of the induction for 4 weeks. Three groups were designed: Control(n=6),diabetic(n=6) and Losartan treatment(n=6) groups. Upro,Ucr in urine and Glu, Scr, BUN in serum were determined after 4wks. Immunohistochemistry combined with semi-quantitive method by computer image-pattern analysis system were used to analyze expression of p-p38 MAPK, p-CREB, FN and LN in renal glomeruli of different groups. Western blot and Flow cytometry were performed to valuate the expression of p-p38 MAPK and p-CREB in different groups. Results In diabetic rats, Losartan suppressed the expression of fibronectin and laminin in glomeruli, which was closely correlated to renal function,renal structure and renal hypertrophy index. In this study ,the activity and expression of p-p38 MAPK and p-CREB were observed in glomeruli in the diabetic group, which were inhibited by Losartan treatment. Conclusion Inhibition of glomerular p38 MAPK signal transduction pathyway may be responsible for the decrement of extracellular matrix accumulation and renal protective effects of losartan in uninephrectomized Wistar rats.