Dewa Yasuaki, Kemmochi Sayaka, Kawai Masaomi, Saegusa Yukie, Harada Tomoaki, Shimamoto Keisuke, Mitsumori Kunitoshi, Kumagai Susumu, Sugita-Konishi Yoshiko, Shibutani Makoto
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Exp Toxicol Pathol. 2011 Jan;63(1-2):17-24. doi: 10.1016/j.etp.2009.09.002. Epub 2009 Sep 27.
To clarify the underlying mechanisms of IgA nephropathy (IgAN) induced by nivalenol (NIV), a trichothecene mycotoxin, we examined the time and dose relationships of glomerular deposition of IgA by NIV in BALB/c mice (Experiment 1), and also evaluated the modification of NIV on spontaneous IgAN in an inbred murine model, a high IgA strain (HIGA), during its early stage of pathogenesis (Experiment 2). In Experiment 1, female BALB/c mice were given a diet containing 0, 12, or 24 ppm concentration of NIV for 4 or 8 weeks. An increase in serum IgA levels was found at 24 ppm from 4 weeks. At week 8 of treatment, dose-dependent increases in serum IgA levels and glomerular deposition of IgA and IgG were observed without accompanying histopathological glomerular changes. On the other hand, in Experiment 2, control HIGA mice exhibited rather high levels of serum IgA as compared with BALB/c mice from 4 weeks of experiment as well as glomerular deposition of IgA and IgG and mesangial proliferation as revealed at week 8. NIV at 24ppm further increased serum IgA in this strain; however, it did not enhance glomerular immunoglobulin deposition or histopathological lesion. These results suggest that NIV-induced increase of serum IgA levels may be primarily responsible for glomerular immunoglobulin deposition; however, NIV does not enhance glomerular IgA deposition that may lead to exacerbation of predisposed IgAN in the short term, irrespective of the further elevation of serum IgA from the high basal levels.
为阐明单端孢霉烯族霉菌毒素雪腐镰刀菌烯醇（NIV）诱发IgA肾病（IgAN）的潜在机制，我们研究了NIV诱导BALB/c小鼠肾小球IgA沉积的时间和剂量关系（实验1），并评估了NIV对近交系小鼠模型（高IgA品系，HIGA）在发病早期自发性IgAN的影响（实验2）。在实验1中，给雌性BALB/c小鼠喂食含0、12或24 ppm浓度NIV的饲料，持续4周或8周。从第4周起，发现24 ppm组血清IgA水平升高。在治疗第8周时，观察到血清IgA水平、IgA和IgG的肾小球沉积呈剂量依赖性增加，且无肾小球组织病理学改变。另一方面，在实验2中，与BALB/c小鼠相比，对照HIGA小鼠从实验第4周起血清IgA水平就相当高，且在第8周时出现IgA和IgG的肾小球沉积以及系膜增生。24 ppm的NIV使该品系小鼠血清IgA进一步升高；然而，它并未增强肾小球免疫球蛋白沉积或组织病理学损伤。这些结果表明，NIV诱导的血清IgA水平升高可能是肾小球免疫球蛋白沉积的主要原因；然而，NIV不会增强肾小球IgA沉积，在短期内不会导致易感IgAN病情加重，尽管血清IgA从高基础水平进一步升高。
