ApoE-/-小鼠肾动脉粥样硬化斑块破裂的肾损害

目的 探讨ApoE^-/-小鼠肾动脉粥样硬化斑块破裂对下游肾脏的损伤机制。 方法 采用ApoE^-/-小鼠建立粥样硬化性肾动脉狭窄(ARAS)动物模型。选择肾动脉狭窄程度 <50％的ApoE^-/-小鼠，按斑块分为破裂组和未破裂组；选择同条件喂养的C57BL/6J 野生型小鼠为对照组。常规检测Scr及尿 N-乙酰-β-氨基葡萄糖苷酶(NAG)活性；Western印迹检测细胞核中核转录因子κBp65（NF-κBp65）、细胞间黏附分子1（ICAM-1）及P-选择素（P-sel）表达； RT-PCR检测白细胞介素6 （IL-6）mRNA表达；免疫组化染色检测巨噬细胞浸润情况。 结果破裂组Scr和尿NAG活性明显升高（均P < 0.01）；肾组织出现病理改变，肾间质中巨噬细胞浸润增加（P < 0.05）；细胞核中NF-κBp65表达增加（P < 0.05）；ICAM-1、P-sel、IL-6 mRNA表达增加（P < 0.05）。未破裂组上述指标与对照组比较，差异无统计学意义（P > 0.05）；肾脏未见明显病理改变。 结论 肾动脉粥样硬化斑块破裂可引起肾脏病理改变和肾功能受损；在粥样硬化性肾动脉狭窄的肾损害机制中，炎性反应是重要因素之一。

Renal damage due to rupture of atherosclerotic plaque of renal artery in ApoE-/- mice

Objective To investigate the mechanism of renal damage due to rupture of atheroselerotic plaque of renal artery in apolipoprotein E (ApoE) knock-out mice. Methods The model for atherosclerotie renal artery stenosis (ARAS) was established by using ApoE knockout mice. The model mice with renal artery stenosis <50% were divided into the plaque rupture group and the non-plaque rupture group. Wild-type C57BL/6J mice were used as the control group. All the mice were raised under the same conditions. The renal arteries and kidneys were collected for the following analysis. Nuclear factor-kappa-Bp65 (NF-kBp65), intercellular adhesion molecule 1 (ICAM-1) and P-selectin (P-sel) were determined by Western blotting. The expression of interleukin 6 (IL-6) mRNA was detected by RT-PCR. Immunohistochemistry was performed by using serial sections to detect F4/80-related macrophages. Urine n-acetyl-β-d-glucosaminidase (NAG) activity was determined by direct enzyme-substrate coloration. Results In comparison with the nonplaque rupture group and the control group, the expression of NF-kBp65 protein in the blood, renal artery and kidney increased significantly in the plaque rupture group (P<0.05). The expression of F4/80, ICAM-1, P-sel, and IL-6 mRNA were increased significantly in the plaque rupture group (P<0.05), as compared with the non-plaque rupture group and the control group. The Ser and the activity of urine NAG in the plaque rupture group were higher than those in the non-plaque rapture group. The expression of NF-KBp65 protein differed insignificantly between the control group and the non-plaque rupture group (P>O.05). The group differences in the expression of F4/80, ICAM-1, P-sel, and IL-6 mRNA were similar to those in the expression of NF-KBp65 protein. The group differences in the activity of urine NAG and the Scr were similar to those in the expression of NF-kBp65 protein. Conclusion Rupture of atherosclerotic plaque of renal artery causes renal pathology change and renal function damage, which is mediated by inflammation.