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高脂饮食诱导ApoE/CD36/SR-A三敲除小鼠肾脏损害及其机制 被引量：1

High fat diet induces renal injury in mice with CD36/SR-A/ApoE KO knockout and its mechanism
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摘要 目的探讨低密度脂蛋白受体相关蛋白(low density lipoprotein receptor-related protein,LRP1)、清道夫受体CD36、SR-A在脂质诱导肾脏损伤中的作用。方法雄性ApoE/CD36/SR-A三敲除小鼠12只,按随机数字表法分为普通组和高脂组。检测血清淀粉样蛋白(serum amyloid A protein,SAA),IL-6、脂质水平及尿蛋白。油红"O"染色及酶法检测肾组织内脂质沉积情况。HE、过碘酸-希夫(periodic acid Schiff reaction,PAS)、马松(Masson)方法观察肾脏形态学改变,定量PCR技术,Western blot与免疫组化技术检测肾组织相关因子水平。结果高脂组脂质水平[TC(51.96±5.60)、LDL(16.79±4.80)mmol/L]显著高于普通组[TC(18.11±3.07)、LDL(3.27±1.79)mmol/L](P<0.05)。肾脏脂质的沉积明显升高,高脂组尿蛋白[(2.90±0.50)mg/ml]显著高于普通组[(1.85±0.18)mg/ml](P<0.05),肾脏病理改变显著,进一步检测发现高脂组上调了LRP1(增高2.23倍)、肾脏Ⅰ型胶原蛋白、转化生长因子(TGF-β)、纤维连接蛋白(Fibronectin)mRNA与蛋白的表达。结论 LRP1可能参与肾脏泡沫细胞的形成及肾脏的损伤,SR-A,CD36不能解释泡沫细胞形成的全部机制。 Objective To study the role of low density lipoprotein receptor-related proteins,CD36 and SR-A,in lipid-mediated renal injury. Methods Male mice with their ApoE/CD36/SR-A knocked out were randomly divided into common diet group and high fat diet group. Levels of serum amyloid A （SAA）,interleukin-6 （IL-6）,lipid and urinary protein were measured. Lipid deposit in renal tissues was detected by enzyme linked immunosorbent assay with oil red O staining. Periodic acid Schiff （PAS） reaction and Masson method were used to observed changes in kidney morphology. PCR,Western blot analysis and immunohistochemistry were used to measure levels of related factors in renal tissue. Results The levels of SAA （TC=51.96±5.60 mmol/L and LDL=16.79±4.80 mmol/L）,lipid deposit in renal tissue,and urinary protein （2.90±0.50 mg/ml） were significantly higher in high fat diet group than those （TC=18.11±3.07 mmol/L and LDL=3.27±1.79 mmol/L,1.85±0.18 mg/ml） in common diet group（P0.05）. The expression levels of low density lipoprotein receptor-related proteins,type Ⅰ collagen protein,TGF-β,and fibronectin mRNA were significantly higher in high diet group than in common diet group （P0.05）. Conclusion Low density lipoprotein receptor-related proteins may play a role in formation of foam cells in kidney and renal injury. However,CD36 and SRA cannot explain the overall mechanism underlying the formation of foam cells in kidney.
作者 徐珍娥 闫凤 阮雄中 陈压西 李秋
机构地区 重庆医科大学附属儿童医院肾内科 重庆医科大学感染性疾病分子生物学教育部重点实验室脂质中心
出处 《第三军医大学学报》 CAS CSCD 北大核心 2010年第17期1828-1833,共6页 Journal of Third Military Medical University
基金 国家自然科学基金重点项目(30772295 30530360) 重庆市自然科学基金重点项目(CSTC2008BA5016 2009BA5080)~~
关键词 脂质 肾小球硬化 ApoE/CD36/SR-A敲小鼠 低密度脂蛋白受体相关蛋白 lipid glomerular sclerosis ApoE/CD36/SR-A KO knocked out mice 1ow density lipoprotein receptor-related protein
分类号 R692.02 [医药卫生—泌尿科学] R151.3 [医药卫生—营养与食品卫生学]
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参考文献16

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共引文献9

同被引文献11

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第三军医大学学报
2010年 第17期

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