Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Kita 18-Nishi 9, Kita-ku, Sapporo060-0818, Japan.
Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
Microsc Microanal. 2021 Aug;27(4):897-909. doi: 10.1017/S143192762100057X.
Diabetes mellitus (DM) is a predisposing factor for renal disorder progression and is referred to as diabetic kidney disease (DKD). However, there are no reports of DKD with an underlying autoimmune disorder. In this study, we compared the pathophysiological changes caused by DM induction after streptozotocin (STZ) injection in comparison with that in a control group receiving citrate buffer (CB) in the autoimmune disease model mice “BXSB/MpJ-Yaa” (Yaa) and the wild-type strain BXSB/MpJ. Both strains showed hyperglycemia after 12 weeks of STZ injection. Interestingly, the Yaa group developed membranous and proliferative glomerulonephritis, which tended to be milder glomerular lesions in the STZ group than in the CB group, as indicated by a decreased mesangial area and ameliorated albuminuria. Statistically, the indices for hyperglycemia and autoimmune abnormalities were negatively and positively correlated with the histopathological parameters for mesangial matrix production and glomerular proliferative lesions, respectively. STZ treatment induced renal tubular anisonucleosis and dilations in both strains, and they were more severe in Yaa. Significantly decreased cellular infiltration was observed in the Yaa group compared to the CB group. Thus, in DKD related to autoimmune nephritis, hyperglycemia modifies its pathology by decreasing the mesangial area and interstitial inflammation and aggravating renal tubular injury.
糖尿病（DM）是肾脏疾病进展的易患因素，被称为糖尿病肾病（DKD）。然而，目前还没有报道称自身免疫性疾病会导致 DKD。在这项研究中，我们比较了链脲佐菌素（STZ）注射后在自身免疫疾病模型小鼠“BXSB/MpJ-Yaa”（Yaa）和野生型 BXSB/MpJ 中 DM 诱导的病理生理变化与对照组（接受柠檬酸盐缓冲液（CB））的变化。两种品系在 STZ 注射 12 周后均出现高血糖。有趣的是，Yaa 组发生了膜性和增生性肾小球肾炎，与 CB 组相比，STZ 组肾小球病变趋于较轻，表现为系膜区面积减少和白蛋白尿改善。统计学分析表明，高血糖和自身免疫异常的指标与系膜基质产生和肾小球增生病变的组织病理学参数呈负相关和正相关。STZ 处理诱导了两种品系的肾小管不均匀核和扩张，在 Yaa 中更严重。与 CB 组相比，Yaa 组的细胞浸润明显减少。因此，在与自身免疫性肾炎相关的 DKD 中，高血糖通过减少系膜区面积和间质炎症以及加重肾小管损伤来改变其病理。
