CALL FOR PAPERS Sex and Gender Differences in Renal Physiology
CALL FOR PAPERS Sex and Gender Differences in Renal Physiology
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DOI：
10.1152/ajprenal.00676.2013
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发表时间：
2014-12-01
影响因子：
4.2
通讯作者：
Brown, Lindsay
中科院分区：
文献类型：
--
作者：
Diwan, Vishal;Small, David;Brown, Lindsay
性别导致慢性肾脏疾病（CKD）和相关心血管疾病的发病率和进展存在差异。为了在雄性和雌性Wistar大鼠（n = 12/组）中诱导肾损伤，使用0.25%腺嘌呤饮食16周。肾功能（血尿素氮、血浆肌酐、蛋白尿）和结构（肾小球损伤、肾小管间质萎缩、纤维化、炎症）;心血管功能（血压、心室僵硬度、血管反应、超声心动图）和结构（心脏纤维化）;血浆睾酮和雌激素浓度;和氧化应激的蛋白质表达[血红素氧合酶-1，炎症在雄性和雌性中比较了TNF-α、纤维化（转化生长因子-β）、ERK 1/2和雌激素受体-α（ER-α）]。尽管肾脏萎缩、炎症和纤维化相似，但喂食腺嘌呤的雌性肾脏功能下降的程度低于喂食腺嘌呤的雄性。血浆雌激素浓度增加，血浆睾酮浓度下降腺嘌呤喂养的男性，与女性的变化较小。肾脏中CKD相关的分子变化在雄性中比雌性更明显，但肾脏中ER-α的表达除外，其在腺嘌呤喂养的雄性中被完全抑制，但在腺嘌呤喂养的雌性中无变化。两种性别都显示出腺嘌呤饮食增加血压，心室僵硬度和心脏纤维化。腺嘌呤对雄性和雌性动物的心血管变化相似，但雄性动物发生了向心性肥大，雌性动物发生了离心性心脏肥大。在腺嘌呤喂养的雄性和雌性大鼠的心脏中，ER-α的表达和ERK 1/2通路的激活增加，部分解释了心脏肥大的变化。总之，由于ER-α的抑制，腺嘌呤诱导的肾损伤可能在雄性中增加
Gender contributes to differences in incidence and progression of chronic kidney disease (CKD) and associated cardiovascular disease. To induce kidney damage in male and female Wistar rats (n = 12/group), a 0.25% adenine diet for 16 wk was used. Kidney function (blood urea nitrogen, plasma creatinine, proteinuria) and structure (glomerular damage, tubulointerstitial atrophy, fibrosis, inflammation); cardiovascular function (blood pressure, ventricular stiffness, vascular responses, echocardiography) and structure (cardiac fibrosis); plasma testosterone and estrogen concentrations; and protein expression for oxidative stress [heme oxygenase-1, inflammation (TNF-alpha), fibrosis (transforming growth factor-beta), ERK1/2, and estrogen receptor-alpha (ER-alpha)] were compared in males and females. Adenine-fed females had less decline in kidney function than adenine-fed males, although kidney atrophy, inflammation, and fibrosis were similar. Plasma estrogen concentrations increased and plasma testosterone concentrations decreased in adenine-fed males, with smaller changes in females. CKD-associated molecular changes in kidneys were more pronounced in males than females except for expression of ER-alpha in the kidney, which was completely suppressed in adenine-fed males but unchanged in adenine-fed females. Both genders showed increased blood pressure, ventricular stiffness, and cardiac fibrosis with the adenine diet. Cardiovascular changes with adenine were similar in males and females, except males developed concentric, and females eccentric cardiac hypertrophy. In hearts from adenine-fed male and female rats, expression of ER-alpha and activation of the ERK1/2 pathway were increased, in part explaining changes in cardiac hypertrophy. In summary, adenine-induced kidney damage may be increased in males due to the suppression of ER-alpha