Renal injury: Similarities and differences in male and female rats with the metabolic syndrome
Renal injury: Similarities and differences in male and female rats with the metabolic syndrome
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DOI：
10.1038/sj.ki.5000406
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发表时间：
2006-06-01
影响因子：
19.6
通讯作者：
Peterson, R.
中科院分区：
文献类型：
--
作者：
Dominguez, J. H.;Wu, P.;Peterson, R.
在人类和大鼠中，代谢综合征并发肾病，并且雄性比雌性更受影响。我们假设雌性大鼠肾小球氧化低密度脂蛋白（oxLDL）受体1（LOX-1）表达减少，伴随肾小球氧化损伤和肾脏炎症。研究了Zucker脂肪糖尿病（ZDF）品系和自发性高血压心力衰竭大鼠（SHHF/Gmi-fa）的第一代（F-1）杂种大鼠的三组肥胖雄性（OM）、肥胖雌性（OF）和瘦雄性（LM），从6周龄至41周龄。OM存在严重的肾脏氧化损伤和肾衰竭。他们的肾小球表达LOX-1，并表现出较重的脂质过氧化物4-羟基壬烯醛（4-HNE）的积累。OM损害了线粒体酶功能，更多的肾纤维化和血管渗漏。对6 - 16周龄的较年轻的LM、OM和OF ZS（ZDF/SHHF F-1杂交大鼠）大鼠进行研究，结果表明OM和OF中未利用的肾脂质相当，尽管年轻的OM有更严重的肾病和炎症。总之，肾小球LOX-1的表达与OM中4-HNE的沉积和肾小球硬化有关。我们推测LOX-1增强肾小球对氧化脂质的摄取和肾脏炎症，导致更大的氧化应激和严重的肾小球硬化。在OF中，肾保护免受脂质氧化剂的影响似乎是由肾小球LOX-1表达减弱和肾脏炎症引起的。
The metabolic syndrome is complicated by nephropathy in humans and rats, and males are more affected than females. We hypothesized that female rats had reduced expression of glomerular oxidized low-density lipoprotein (oxLDL) receptor 1 (LOX-1), attendant glomerular oxidant injury, and renal inflammation. Three groups, obese males (OM), obese females (OF), and lean males (LM) of first-generation (F-1) hybrid rats derived from the Zucker fatty diabetic (ZDF) strain and the spontaneous hypertensive heart failure rat (SHHF/Gmi-fa) were studied from 6 to 41 weeks of age. OM had severe renal oxidant injury and renal failure. Their glomeruli expressed the LOX-1, and exhibited heavier accumulation of the lipid peroxide 4-hydroxynonenal (4-HNE). OM had compromised mitochondrial enzyme function, more renal fibrosis, and vascular leakage. Younger LM, OM, and OF ZS (ZDF/SHHF F-1 hybrid rat) rats, studied from 6 to 16 weeks of age, showed that unutilized renal lipids were comparable in OM and OF, although young OM had worse nephropathy and inflammation. In conclusion, glomerular LOX-1 expression is coupled to deposits of 4-HNE and glomerulosclerosis in OM. We presume that LOX-1 enhances glomerular uptake of oxidized lipids and renal inflammation, causing greater oxidant stress and severe glomerulosclerosis. In OF, renal protection from lipid oxidants appears to be conferred by blunted glomerular LOX-1 expression and renal inflammation.