Kemmochi Sayaka, Hayashi Hitomi, Taniai Eriko, Hasumi Keiji, Sugita-Konishi Yoshiko, Kumagai Susumu, Mitsumori Kunitoshi, Shibutani Makoto
J Toxicol Pathol. 2012 Jun;25(2):149-54. doi: 10.1293/tox.25.149.
Activators of tissue proteolysis including Stachybotrys microspora triprenyl phenol (SMTP)-7 are a new class of agents that are expected to be effective for amelioration of chronic tissue destructive diseases. The present study was performed to examine whether SMTP-7 is effective for the amelioration or protection of early-stage IgA nephropathy (IgAN) induced by nivalenol (NIV) in female BALB/c mice. In Experiment 1, mice were administered NIV at 24 ppm in diet for 8 weeks, and during the NIV treatment, they were intraperitoneally injected with SMTP-7 (10 mg/kg) three times a week. In Experiment 2, mice were injected similarly with SMTP-7 during the last 4 weeks of a 16-week NIV treatment. Immunofluorescence analysis revealed an inhibitory effect of SMTP-7 on the glomerular deposition of IgA in Experiment 1; however, it was ineffective in Experiment 2. On the other hand, SMTP-7 did not affect the serum concentration of IgA in both experiments. These results suggest that SMTP-7 has a potential to decrease the progression of IgAN induced by NIV through inhibition of local accumulation of IgA in the glomerular mesangium, while it was ineffective for suppression of IgA production. On the other hand, SMTP-7 was found to be ineffective for already deposited IgA, suggesting that SMTP-7 may not be effective for ameliorating advanced IgAN.
包括小孢根霉三萜酚(SMTP)-7在内的组织蛋白水解激活剂是一类新型药物,有望有效改善慢性组织破坏性疾病。本研究旨在检测SMTP-7对改善或保护雌性BALB/c小鼠中由雪腐镰刀菌烯醇(NIV)诱导的早期IgA肾病(IgAN)是否有效。在实验1中,给小鼠喂食含24 ppm NIV的饲料8周,在NIV治疗期间,每周给它们腹腔注射3次SMTP-7(10 mg/kg)。在实验2中,在为期16周的NIV治疗的最后4周,给小鼠同样注射SMTP-7。免疫荧光分析显示,在实验1中SMTP-7对IgA在肾小球的沉积有抑制作用;然而,在实验2中无效。另一方面,在两个实验中SMTP-7均未影响血清IgA浓度。这些结果表明,SMTP-7有可能通过抑制IgA在肾小球系膜中的局部蓄积来降低NIV诱导的IgAN的进展,而对抑制IgA产生无效。另一方面,发现SMTP-7对已经沉积的IgA无效,这表明SMTP-7可能对改善晚期IgAN无效。