Sex Differences in Renal Inflammation and Injury in High-Fat Diet-Fed Dahl Salt-Sensitive Rats.

Sex Differences in Renal Inflammation and Injury in High-Fat Diet-Fed Dahl Salt-Sensitive Rats.
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DOI:
10.1161/hypertensionaha.118.11485
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发表时间:
2018-11
期刊:
Hypertension (Dallas, Tex. : 1979)
影响因子:
--
通讯作者:
Xu H
Xu H
中科院分区:
其他
文献类型:
--
作者:
Fernandes R;Garver H;Harkema JR;Galligan JJ;Fink GD;Xu H

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我们研究了性别对高脂肪饮食引起的Dahl盐敏感大鼠和Sprague Dawley大鼠肾脏改变的影响。在达尔大鼠中,高脂肪饮食(从断奶开始的24-26周内,60%的卡路里来自脂肪)与对照组饮食(10%的卡路里来自脂肪)相比,雄性和雌性的血压均显著升高。与对照组相比,高脂饮食的雄性达尔大鼠在饲养10周和24周时表现出进行性肾脏组织损伤,肾脏巨噬细胞浸润适度增加。无论饮食如何,雌性Dahl大鼠的肾损伤程度较低,巨噬细胞浸润较少(17周除外)。两种饮食的雄性达尔大鼠都表现出肾脏t细胞数量的逐渐增加,而在雌性中没有观察到这种模式。高脂肪饮食本身对肾t细胞数量没有显著影响。24周时,雄性达尔大鼠的肾T-reg细胞比例低于雌性。肾巨噬细胞和t细胞浸润与最终MAP水平在男性中高度相关,而在女性中不相关。高脂饲料喂养24周后,Sprague Dawley大鼠血压正常,无明显肾损伤/炎症。综上所述,高脂饲料喂养对Sprague Dawley大鼠的动脉血压没有升高作用,但对雄性和雌性Dahl盐敏感大鼠的高血压均有强烈的促进作用。然而,只有达尔男性表现出与血压相关的肾脏炎症和损伤。维持T-reg比率可能对高血压相关的肾损伤/炎症有保护作用,但对高脂饮食引起的高血压没有保护作用。
We examined the impact of sex on high fat diet induced renal alterations in Dahl salt sensitive and Sprague Dawley rats. In Dahl rats, high fat diet (60% kcal from fat for 24–26 weeks starting at weaning) significantly and equally increased blood pressure in males and females when compared to rats fed a control diet (10% kcal from fat). Male Dahl rats on high fat diet exhibited progressive renal histological injury, and moderately increased renal macrophage infiltration at 10 and 24 weeks of feeding when compared to males on control diet. Female Dahl rats had lower grade renal injury and less macrophage infiltration (except at 17 weeks) than males regardless of diet. Male Dahl rats on both diets showed progressively increasing numbers of renal T-cells, a pattern not observed in females. High fat diet per se did not significantly affect renal T-cell number. Male Dahl rats had lower renal T-reg cell ratio than females at 24 weeks. Renal macrophage and T-cell infiltrations were highly correlated to final MAP levels in males but not in females. Sprague Dawley rats fed high fat diet were normotensive without significant renal injury/inflammation after 24 weeks of feeding. In summary, high fat diet feeding fails to increase arterial blood pressure in Sprague Dawley rats, but strongly promotes hypertension in both male and female Dahl salt sensitive rats. Only Dahl males, however, exhibited blood pressure-associated renal inflammation and injury. Maintenance of T-reg ratio may protect against hypertension associated renal injury/inflammation but not high fat diet-induced hypertension.