Ma Shuangtao, Zhu Xiang-Yang, Eirin Alfonso, Woollard John R, Jordan Kyra L, Tang Hui, Lerman Amir, Lerman Lilach O
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota; Department of Cardiology, Chengdu Military General Hospital, Chengdu, Sichuan, People's Republic of China.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
J Urol. 2016 Apr;195(4 Pt 1):1152-9. doi: 10.1016/j.juro.2015.08.105. Epub 2015 Sep 28.
Perirenal fat is associated with poor blood pressure control and chronic kidney disease but the underlying mechanisms remain elusive. We tested the hypothesis that perirenal fat impairs renal arterial endothelial function in pigs with obesity-metabolic derangements.
We studied 14 domestic pigs after 16 weeks of a high fat/high fructose diet (obesity-metabolic derangement group) or standard chow (lean group). Renal blood flow, glomerular filtration rate and visceral fat volumes were studied in vivo by computerized tomography. Renal arterial endothelial function was also studied ex vivo in organ baths.
Pigs with obesity-metabolic derangements demonstrated increased body weight, blood pressure, cholesterol and intra-abdominal fat compared to lean pigs and perirenal fat volume was significantly larger. Renal blood flow and glomerular filtration rate were markedly elevated while urinary protein level was preserved. Ex vivo acetylcholine induced, endothelium dependent vasodilation of renal artery rings was substantially impaired in pigs with obesity-metabolic derangements compared to lean pigs. Endothelial function was further blunted in obesity-metabolic derangement and lean arterial rings by incubation with perirenal fat harvested from pigs with obesity-metabolic derangements but not from lean pigs. It was restored by inhibiting tumor necrosis factor-α. Perirenal fat from pigs with obesity-metabolic derangements also showed increased pro-inflammatory macrophage infiltration and tumor necrosis factor-α expression.
In pigs with obesity-metabolic derangements perirenal fat directly causes renal artery endothelial dysfunction, which is partly mediated by tumor necrosis factor-α.
肾周脂肪与血压控制不佳和慢性肾脏病相关，但其潜在机制仍不清楚。我们检验了这样一个假设，即肾周脂肪会损害伴有肥胖-代谢紊乱的猪的肾动脉内皮功能。
我们对14头家猪进行了研究，其中16周给予高脂/高果糖饮食（肥胖-代谢紊乱组），另外一组给予标准饲料（ lean组）。通过计算机断层扫描在体内研究肾血流量、肾小球滤过率和内脏脂肪体积。还在离体器官浴中研究肾动脉内皮功能。
与 lean组猪相比，肥胖-代谢紊乱组猪体重、血压、胆固醇和腹内脂肪增加，肾周脂肪体积显著更大。肾血流量和肾小球滤过率明显升高，而尿蛋白水平保持不变。与 lean组猪相比，肥胖-代谢紊乱组猪离体乙酰胆碱诱导的肾动脉环内皮依赖性血管舒张功能明显受损。肥胖-代谢紊乱组和 lean组动脉环与来自肥胖-代谢紊乱组猪而非 lean组猪的肾周脂肪一起孵育后，内皮功能进一步减弱。通过抑制肿瘤坏死因子-α可使其恢复。肥胖-代谢紊乱组猪的肾周脂肪还显示促炎巨噬细胞浸润增加和肿瘤坏死因子-α表达增加。
在伴有肥胖-代谢紊乱的猪中，肾周脂肪直接导致肾动脉内皮功能障碍，这部分是由肿瘤坏死因子-α介导的。
