Yashima Akihito, Mizuno Masashi, Yuzawa Yukio, Shimada Koki, Suzuki Norihiko, Tawada Hideo, Sato Waichi, Tsuboi Naotake, Maruyama Shoichi, Ito Yasuhiko, Matsuo Seiichi, Ohno Tamio
Division of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Clin Exp Nephrol. 2017 Aug;21(4):589-596. doi: 10.1007/s10157-016-1339-8. Epub 2016 Nov 4.
Malaria is an important tropical disease and has remained a serious health problem in many countries. One of the critical complications of malarial infection is renal injury, such as acute renal failure and chronic glomerulopathy. Few animal models of nephropathy related to malarial infection have been reported. Therefore, we developed and investigated a novel malarial nephropathy model in mice infected by murine malaria parasites.
NC mice and C57BL/6J mice were infected with Ttwo different murine malaria parasites, Plasmodium (P.) chabaudi AS and P. yoelii 17X. After the infection, renal pathology and blood and urinary biochemistry were analyzed.
NC mice infected by the murine malaria parasite P. chabaudi AS, but not P. yoelii 17X, developed mesangial proliferative glomerulonephritis with endothelial damage, and decreased serum albumin concentration and increased proteinuria. These pathological changes were accompanied by deposition of immunoglobulin G and complement component 3, mainly in the mesangium until day 4 and in the mesangium and glomerular capillaries from day 8. On day 21, renal pathology developed to focal segmental sclerosis according to light microscopy. In C57BL/6J mice, renal injuries were not observed from either parasite infection.
The clinical and pathological features of P. chabaudi AS infection in NC mice might be similar to quartan malarial nephropathy resulting from human malaria parasite P. malariae infection. The NC mouse model might therefore be useful in analyzing the underlying mechanisms and developing therapeutic approaches to malaria-related nephropathy.
疟疾是一种重要的热带疾病，在许多国家仍然是一个严重的健康问题。疟疾感染的关键并发症之一是肾损伤，如急性肾衰竭和慢性肾小球病。很少有关于疟疾感染相关肾病动物模型的报道。因此，我们建立并研究了一种由鼠疟原虫感染小鼠的新型疟疾肾病模型。
将NC小鼠和C57BL/6J小鼠分别感染两种不同的鼠疟原虫，即查巴迪疟原虫AS株（P. chabaudi AS）和约氏疟原虫17X株（P. yoelii 17X）。感染后，分析肾脏病理学以及血液和尿液生化指标。
感染鼠疟原虫查巴迪疟原虫AS株而非约氏疟原虫17X株的NC小鼠，出现了伴有内皮损伤的系膜增生性肾小球肾炎，血清白蛋白浓度降低，蛋白尿增加。这些病理变化伴随着免疫球蛋白G和补体成分3的沉积，主要在第4天前沉积于系膜区，从第8天起沉积于系膜区和肾小球毛细血管。在第21天，根据光学显微镜观察，肾脏病理发展为局灶节段性硬化。在C57BL/6J小鼠中，两种寄生虫感染均未观察到肾损伤。
NC小鼠感染查巴迪疟原虫AS株的临床和病理特征可能类似于人类疟原虫三日疟原虫感染导致的三日疟肾病。因此，NC小鼠模型可能有助于分析疟疾相关肾病的潜在机制并开发治疗方法。
