Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.
Am J Physiol Renal Physiol. 2020 May 1;318(5):F1074-F1085. doi: 10.1152/ajprenal.00598.2019. Epub 2020 Mar 9.
Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by circulating autoantibodies, prevalent hypertension, renal injury, and cardiovascular disease. Onset of the disease often occurs in young women of childbearing age. Although kidney involvement is common to patients with SLE, little is known about temporal changes in renal hemodynamic function and its relationship to the pathogenesis of hypertension during autoimmune diseases. We hypothesized that the loss of immunological tolerance and subsequent production of autoantibodies in SLE leads to impaired renal hemodynamic function that precedes the development hypertension. Female NZBWF1 (SLE) mice and female NZW/LacJ (control) mice were instrumented with carotid artery and jugular vein catheters to determine mean arterial pressure (MAP) and glomerular filtration rate, respectively, at ages of 15, 20, 24, 28, 31, and 34 wk. In addition, urinary albumin excretion, blood urea nitrogen, circulating autoantibodies, and glomerulosclerosis were assessed at each age. Levels of circulating autoantibodies are increased between 24 and 28 wk of age in NZBWF1 mice and were significantly greater than in control mice. Glomerular filtration rate was significantly increased at 28 wk of age in NZBWF1 mice followed by a sharp decline at 34 wk of age. NZBWF1 mice had an increase in MAP that occurred by 34 wk of age. These data show that changes in circulating autoantibodies, renal hemodynamic function, and glomerular injury occur in NZBWF1 mice before changes in MAP, suggesting an important mechanistic role for autoimmunity to directly impair renal hemodynamic function and promote the development of hypertension.
系统性红斑狼疮（SLE）是一种慢性多系统自身免疫性疾病，其特征是循环自身抗体、普遍存在的高血压、肾脏损伤和心血管疾病。疾病的发作通常发生在育龄期的年轻女性中。尽管肾脏受累是 SLE 患者的常见现象，但对于自身免疫性疾病期间肾血流动力学功能的时间变化及其与高血压发病机制的关系知之甚少。我们假设 SLE 中免疫耐受的丧失和随后自身抗体的产生导致肾血流动力学功能受损，这先于高血压的发展。15、20、24、28、31 和 34 周龄时，给 NZBWF1（SLE）雌性小鼠和 NZW/LacJ（对照）雌性小鼠安置颈动脉和颈静脉导管，分别确定平均动脉压（MAP）和肾小球滤过率（GFR）。此外，在每个年龄评估尿白蛋白排泄、血尿素氮、循环自身抗体和肾小球硬化。在 NZBWF1 小鼠中，24 至 28 周龄时循环自身抗体水平升高，明显高于对照小鼠。NZBWF1 小鼠的肾小球滤过率在 28 周龄时显著增加，随后在 34 周龄时急剧下降。NZBWF1 小鼠的 MAP 增加发生在 34 周龄时。这些数据表明，在 MAP 发生变化之前，循环自身抗体、肾血流动力学功能和肾小球损伤在 NZBWF1 小鼠中发生变化，这表明自身免疫在直接损害肾血流动力学功能和促进高血压发展方面起着重要的机制作用。
