Abstract 15250: Increased CD81 is Associated With Enhanced Apoptosis in Acute Kidney Injuries Induced by Candesartan/Low Salt Diet

Abstract

Introduction: Our previous studies have demonstrated that the upregulation of renal CD81 (cluster of differentiation 81), contributes to the sustained hypertension observed in LPS-preeclampsia rats with kidney injuries. Candesartan (Can) lowers blood pressure by selectively blocking type 1 angiotensin II receptors and results in acute kidney injury (AKI) when used together with dietary sodium restriction. Various cell deaths including apoptosis and necrosis are involved in the pathogenesis of AKI. Hypothesis: Renal CD81 may increased in candesartan/low salt diet(LS+Can) model via activation of apoptosis. Methods: Male SD rats aged 8-10 weeks were fed with LS (0.01% NaCl) or normal salt diets (NS, 0.8% NaCl) (6-10rats/group) respectively for 7 days.All rats were intraperitoneally injected with candesartan (1mg/kg/d) simultaneously.Systolic blood pressure(SBP) was monitored with tail-cuff method.The rats were sacrificed by over-anesthesia after the samples of blood and urine (metabolic cage) were collected.The kidneys were immediately removed for immunoblotting, and TUNEL(TdT-mediated dUTP Nick-End Labeling) measurements.P<0.05 was considered significant for 2 group comparison with t-test. Results: Compared with rats on NS+Can, the serum creatinine (20.3±0.3 vs 50.8±4.2 mmol/L) and BUN(4.05±0.2 vs 18.6±2.5 mmol/L) were more than doubled in LS+Can rats ;Creatinine clearance was decreased (100±4.1 vs 40.8±3.7ml/min); systolic blood pressures was lowered slightly (101.7±1.7 vs 88.9±2.7mmHg, n=7-8). Renal CD81 protein abundance by immunoblotting was increased (258.8±52.4,% of control, n=6/group,p<0.05, same as below).At the same time, there were increases in apoptosis-associated proteins including bax(312.6±71.5),caspase-3(124.6±6) ,cleaved caspase3(133.8±9.6) in Can+LS group.The rate of tunel-positive cells was elevated in the Can+LS group. (100.0±8.5 vs 482.72±59.4,p<0.05,n=10/group).However, necrosis-related inflammatory factors, including Interleukin-6,tumor necrosis factor-α, were not affected in the rat kidneys from LS+Can treated rats. Conclusions: Our findings suggest that Increased CD81 may be associated with enhanced apoptosis in rat kidneys with acute kidney injuries.