Aging-related kidney damage is associated with a decrease in klotho expression and an increase in superoxide production
Aging-related kidney damage is associated with a decrease in klotho expression and an increase in superoxide production
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DOI：
10.1007/s11357-010-9176-2
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发表时间：
2011-09-01
期刊：
影响因子：
--
通讯作者：
Sun, Zhongjie
中科院分区：
文献类型：
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作者：
Zuo, Zhong;Lei, Han;Sun, Zhongjie
本研究的目的是确定老年大鼠肾脏Klotho、ET受体和超氧化物歧化产物的变化，以及这些变化在老年认知障碍大鼠中是否加剧。老年大鼠20只(雄性，27月龄)，按认知功能测试分为老年损伤组(n=9)和老年正常组(n=11)。一组12月龄大鼠(n=10)作为青年正常组。老年受损组血清肌酐显著升高，提示肾功能受损。老年大鼠肾小球硬化，肾小管间质纤维化。这些病理改变在老年认知受损的动物中比在认知正常的老年动物中明显加重。值得注意的是，老年大鼠肾皮质和髓质中Klotho蛋白的表达显著减少。老年大鼠肾脏IL-6、NOX2、ETA受体蛋白表达增加，超氧化物歧化产物生成增加，线粒体超氧化物歧化酶(MnSOD)、ETB受体表达降低。有趣的是，这些变化在老年受损的大鼠中比在老年正常的大鼠中更明显。综上所述，认知损害的老年大鼠与衰老相关的肾损害加重。Klotho、ETB和MnSOD在增龄性肾损伤中表达下调，而ETA、IL-6、NOX2和超氧化物歧化产物表达上调。这些变化在认知障碍的大鼠中更加明显。
The purpose of this study was to determine changes in klotho, endothelin (ET) receptors, and superoxide production in kidneys of aged rats and whether these changes are exacerbated in aged rats with cognitive impairment. Twenty aged rats (male, 27 months) were divided into an Old Impaired group (n = 9) and an Old Intact group (n = 11) according to a cognitive function test. A group of 12-month-old rats (n = 10) was used as a Young Intact group. Serum creatinine was increased significantly in the Old Impaired group, suggesting impaired renal function. Aged rats showed glomerulosclerosis and tubulointerstitialfibrosis. These pathological changes were markedly aggravated in the old cognitively impaired than in the old cognitively intact animals. Notably, aged rats demonstrated a significant decrease in klotho protein expression in renal cortex and medulla. Protein expression of IL-6, Nox2, ETa receptors and superoxide production were increased whereas mitochondrial SOD (MnSOD) and ETb receptors expression were decreased in kidneys of the aged rats. Interestingly, these changes were more pronounced in the old impaired than in the old intact rats. In conclusion, the aging-related kidney damage was exacerbated in aged rats with cognitive impairment. Klotho, ETB, and MnSOD were downregulated but ETa, IL-6, Nox2, and superoxide production were upregulated in the aging-related kidney damage. These changes were more pronounced in rats with cognitive impairment.