Yamaleyeva Liliya M, Pendergrass Karl D, Pirro Nancy T, Gallagher Patricia E, Groban Leanne, Chappell Mark C
Hypertension & Vascular Research Center, Wake Forest University Health Sciences, Winston-Salem, NC 27157-1095, USA.
Am J Physiol Heart Circ Physiol. 2007 Oct;293(4):H2064-71. doi: 10.1152/ajpheart.00427.2007. Epub 2007 Jul 13.
Studies in experimental animals and younger women suggest a protective role for estrogen; however, clinical trials may not substantiate this effect in older females. Therefore, the present study assessed the outcome of ovariectomy in older mRen2. Lewis rats subjected to a high-salt diet for 4 wk. Intact or ovariectomized (OVX, 15 wk of age) mRen2. Lewis rats were aged to 60 wk and then placed on a high-salt (HS, 8% sodium chloride) diet for 4 wk. Systolic blood pressures were similar between groups [OVX 169 +/- 6 vs. Intact 182 +/- 7 mmHg; P = 0.22] after the 4-wk diet; however, proteinuria [OVX 0.8 +/- 0.2 vs. Intact 11.5 +/- 2.6 mg/mg creatinine; P < 0.002, n = 6], renal interstitial fibrosis, glomerular sclerosis, and tubular casts were lower in OVX vs. Intact rats. Kidney injury molecule-1 mRNA, a marker of tubular damage, was 53% lower in the OVX HS group. Independent from blood pressure, OVX HS rats exhibited significantly lower cardiac (24%) and renal (32%) hypertrophy as well as lower C-reactive protein (28%). Circulating insulin-like growth factor-I (IGF-I) levels were not different between the Intact and OVX groups; however, renal cortical IGF-I mRNA and protein were attenuated in OVX rats [P < 0.05, n = 6]. We conclude that ovariectomy in the older female mRen2. Lewis rat conveys protection against salt-dependent increase in renal injury.
对实验动物和年轻女性的研究表明雌激素具有保护作用;然而,临床试验可能无法证实这种作用在老年女性中也存在。因此,本研究评估了高盐饮食4周的老年mRen2. Lewis大鼠卵巢切除术后的结果。将完整或卵巢切除(15周龄)的mRen2. Lewis大鼠饲养至60周龄,然后给予高盐(HS,8%氯化钠)饮食4周。4周饮食后,各组间收缩压相似[卵巢切除组169±6 vs. 完整组182±7 mmHg;P = 0.22];然而,卵巢切除组大鼠的蛋白尿[卵巢切除组0.8±0.2 vs. 完整组11.5±2.6 mg/mg肌酐;P < 0.002,n = 6]、肾间质纤维化、肾小球硬化和肾小管管型均低于完整组大鼠。肾小管损伤标志物肾损伤分子-1 mRNA在卵巢切除高盐组中降低了53%。与血压无关,卵巢切除高盐组大鼠的心脏肥大(24%)和肾脏肥大(32%)明显较低,C反应蛋白也较低(28%)。完整组和卵巢切除组之间循环胰岛素样生长因子-I(IGF-I)水平无差异;然而,卵巢切除组大鼠肾皮质IGF-I mRNA和蛋白水平降低[P < 0.05,n = 6]。我们得出结论,老年雌性mRen2. Lewis大鼠卵巢切除可防止盐依赖性肾损伤增加。