Inflammatory stress exacerbates lipid-mediated renal injury in ApoE/CD36/SRA triple knockout mice
Inflammatory stress exacerbates lipid-mediated renal injury in ApoE/CD36/SRA triple knockout mice
复制标题
炎症应激加剧 ApoE/CD36/SRA 三重敲除小鼠中脂质介导的肾损伤
DOI：
10.1152/ajprenal.00341.2010
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发表时间：
2011-10-01
影响因子：
4.2
通讯作者：
Ruan, Xiong Z.
中科院分区：
文献类型：
--
作者：
Xu, Zhen E.;Chen, Yaxi;Ruan, Xiong Z.
徐泽，陈毅，黄安，Varghese Z, Moorhead JF，闫峰，Powis SH，李强，阮小忠。炎症应激加重ApoE/CD36/SRA三敲除小鼠脂质介导的肾损伤。[J] .中国生物医学工程学报，2016,31(4):713- 722。首次发表于2011年7月27日；doi: 10.1152 / ajprenal.00341.2010。-脂质和炎症在肾脏疾病的进展中都起着重要作用。本研究旨在探讨炎症是否通过LDL受体（LDLr）加剧脂质积累，从而导致C57BL/6J小鼠、载脂蛋白E （ApoE）敲除（KO）小鼠和ApoE/CD36/清除率受体A三重KO小鼠肾损伤。小鼠皮下注射酪蛋白诱导炎症应激。14周后，采集晚期血样进行肾功能、血脂、淀粉样蛋白A （SAA）和IL-6检测。油红O染色观察肾脏脂质积累。检测肾组织中纤维原分子的表达。与对照组相比，所有注射酪蛋白的小鼠血清SAA和IL-6均显著升高。酪蛋白注射降低了三种类型小鼠的血清总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇，并引起肾脏脂质积累。与对照组相比，炎症小鼠LDLr及其调控蛋白SREBP 2和SREBP裂解激活蛋白（SCAP）的表达上调。酪蛋白注射诱导肾纤维化，并伴有纤维化分子的表达增加。这些数据表明，炎症通过SCAP-SREBP2-LDLr途径将脂质从血浆转移到肾脏，从而加剧了肾脏中的脂质积累，并导致肾脏损伤。由炎症引起的低血胆固醇水平可能与慢性肾纤维化的高风险有关。
Xu ZE, Chen Y, Huang A, Varghese Z, Moorhead JF, Yan F, Powis SH, Li Q, Ruan XZ. Inflammatory stress exacerbates lipid-mediated renal injury in ApoE/CD36/SRA triple knockout mice. Am J Physiol Renal Physiol 301: F713-F722, 2011. First published July 27, 2011; doi:10.1152/ajprenal.00341.2010.-Both lipids and inflammation play important roles in the progression of kidney disease. This study was designed to investigate whether inflammation exacerbates lipid accumulation via LDL receptors (LDLr), thereby causing renal injury in C57BL/6J mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE/CD36/scavenger receptor A triple KO mice. The mice were given a subcutaneous casein injection to induce inflammatory stress. After 14 wk, terminal blood samples were taken for renal function, lipid profiles, amyloid A (SAA), and IL-6 assays. Lipid accumulation in kidneys was visualized by oil red O staining. Fibrogenic molecule expression in kidneys was examined. There was a significant increase in serum SAA and IL-6 in the all casein-injected mice compared with respective controls. Casein injection reduced serum total cholesterol, LDL cholesterol, and HDL cholesterol and caused lipid accumulation in kidneys from three types of mice. The expression of LDLr and its regulatory proteins sterol-responsive element-binding protein (SREBP) 2 and SREBP cleavage-activating protein (SCAP) were upregulated in inflamed mice compared with controls. Casein injection induced renal fibrosis accompanied by increased expression of fibrogenic molecules in the triple KO mice. These data imply that inflammation exacerbates lipid accumulation in the kidney by diverting lipid from the plasma to the kidney via the SCAP-SREBP2-LDLr pathway and causing renal injury. Low blood cholesterol levels, resulting from inflammation, may be associated with high risk for chronic renal fibrosis.