Dwyer T M, Banks S A, Alonso-Galicia M, Cockrell K, Carroll J F, Bigler S A, Hall J E
Departments of Physiology and Biophysics and Pathology, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Kidney Int. 2000 Aug;58(2):721-9. doi: 10.1046/j.1523-1755.2000.00218.x.
Obese individuals have an expanded interstitium in the renal inner medulla (IM), which stains positively with periodic acid-Schiff and Alcian blue. In obese dogs, the IM is also expanded, with hyaluronan (HA) content being 2.4 times control.
We determined the anatomic pattern of renal HA deposition following weight gain, using an animal model of obesity consisting of young rabbits (N = 10), representing animals entering into the study, lean rabbits (N = 19), fed a control diet, and obese rabbits (N = 19), fed a high-fat diet (15% fat, by fortifying with corn oil and lard, in a ratio of 2:1) for two to three months. Tissue was papain digested, and HA was recovered in a phosphate or a Tris buffer and detected by an indirect immunoabsorbent competition assay.
Rabbits fed a high-fat diet for 8 to 12 weeks gained weight (37%) and became mildly hypertensive (10 mm Hg). In lean rabbits, HA was low in the renal cortex (6 +/- 30 microg/g tissue), increased steadily across the outer medulla (OM; 79 +/- 28 microg/g tissue) and was uniformly high in the IM (192 +/- 28 microg/g tissue) when recovered in a Tris buffer; these levels of tissue HA did not change during the three-month period of dietary intervention. In obese rabbits, the renal medullary interstitium was expanded and stained intensely with periodic acid Schiff and Alcian blue, and tissue HA was elevated in the IM (448 +/- 25 microg/g tissue) but not the cortex (5 +/- 25 microg/g tissue) or the OM (85 +/- 25 microg/g tissue). The significant difference was due to those IM samples taken from the renal papilla; IM samples from the body of the kidney did not significantly differ among the lean, obese, and young rabbits.
The elevated renal HA associated with weight gain is limited to the IM and occurs most consistently in the papilla, which is the region of the kidney that is most vulnerable to distention caused by elevated renal interstitial hydrostatic pressure.
肥胖个体肾内髓质(IM)的间质扩张,经高碘酸-希夫染色和阿尔辛蓝染色呈阳性。在肥胖犬中,IM也会扩张,透明质酸(HA)含量是对照组的2.4倍。
我们使用肥胖动物模型来确定体重增加后肾脏HA沉积的解剖模式,该模型包括幼兔(N = 10),代表进入研究的动物;瘦兔(N = 19),喂食对照饮食;肥胖兔(N = 19),喂食高脂饮食(15%脂肪,通过用玉米油和猪油按2:1的比例强化)两到三个月。组织经木瓜蛋白酶消化,HA在磷酸盐或Tris缓冲液中回收,并通过间接免疫吸附竞争测定法检测。
喂食高脂饮食8至12周的兔子体重增加(37%)并出现轻度高血压(10 mmHg)。在瘦兔中,当在Tris缓冲液中回收时,肾脏皮质中的HA含量较低(6±30μg/g组织),在外髓质(OM)中稳定增加(79±28μg/g组织),在IM中均匀较高(192±28μg/g组织);在三个月的饮食干预期间,这些组织HA水平没有变化。在肥胖兔中,肾髓质间质扩张,经高碘酸希夫染色和阿尔辛蓝染色强烈,组织HA在IM中升高(448±25μg/g组织),但在皮质(5±25μg/g组织)或OM(85±25μg/g组织)中未升高。显著差异是由于那些取自肾乳头的IM样本;来自肾体的IM样本在瘦兔、肥胖兔和幼兔之间没有显著差异。
与体重增加相关的肾脏HA升高仅限于IM,并且最一致地发生在肾乳头,肾乳头是肾脏中最易受肾间质静水压升高引起的扩张影响的区域。