摘要Background Intrarenal activation of the renin angiotensin system (RAS) plays an important role in mediating renal fibrosis. Both angiotensin converting enzyme inhibitors (ACEIs) and angiotensin I (Ang Ⅱ) receptor antagonists have been shown to exert a protective role against diabetic and nondiabetic nephropathy. However, the exact mechanism of how blocking local RAS prevents renal fibrosis is unclear. The present study was to investigate the influence of a new Ang Ⅱ receptor antagonist, irbesartan (Irb), on Ang Ⅱ-induced hypertrophy in human proximal tubular cell line (HK2).Methods The cell line, HK-2, was grown in Dulbeccos's Modified Eagle's Medium containing 10%heat-inactivated fetal calf serum. After rested in serum-free medium for 24 hours, the effects of Irb on Ang Ⅱ (10-7 mol/L)-induced [3H]-Ieucine incorporation, total protein content (measured by the Coomassie brilliant blue G250 method), and change in cell size (determined by scanning electron microscopy) were observed. The influence of Irb on the cell cycle was analyzed by fluorescence activated cell sorter (FACS) flow cytometry.Results Ang Ⅱ induced cell hypertrophy in a time and dose dependent manner. Stimulation of cells with Ang Ⅱ for 48 hours resulted in a increase in [ 3 H ] -leucine incorporation [ 0 hour: (5584 ± 1016)cpm/105cells vs 48 hours: (10741 ± 802) cpm/105cells, P＜0. 05 ], which was significantly attenuated by treatment with Irb. Ang Ⅱ significantly increased the total protein content in HK-2 cells [control: (0. 169 ±0. 011) mg/105cells vs Ang Ⅱ group: (0. 202 ±0. 010) mg/105 cells, P＜0.05],which was also markedly inhibited by cotreatment with Irb (P ＜0. 01). Scanning electron microscopy showed that Ang Ⅱ induced an increase in average physical cell size, which was significantly inhibited by Irb [control: (11.92 ±1.62)μm; Ang Ⅱ group: (20. 63 ±3.83) μm; Ang Ⅱ +lrb group: (13.59±3. 15) μm; P ＜ 0.01 vs control, respectively]. Furthermore, flow cytometry revealed that Ang Ⅱarrested cells in the G0-G1 phase, which was significantly reversed by treatment with Irb [ G0-G1 cells in Ang Ⅱ group: (76. 09 ±1.82)%, in Ang Ⅱ +lrb group: (67. 00 ±2.52)%, P＜0.05].Conclusion Irb can inhibit Ang Ⅱ-inducedhypertrophy in HK-2 cells.