ATRA 通过下调阿霉素诱导肾小球硬化大鼠 TRPC6 减轻蛋白尿。
ATRA attenuate proteinuria via downregulation of TRPC6 in glomerulosclerosis rats induced by adriamycin.
机构信息
a Department of Pediatric Nephrology , The First Affiliated Hospital of GuangXi Medical University , Nanning , China.
b Department of Pediatric , Affiliated Hospital of Hebei University , Baoding , China.
出版信息
Ren Fail. 2018 Nov;40(1):266-272. doi: 10.1080/0886022X.2018.1456459.
OBJECTIVE
In this research, we explored the molecular mechanism of proteinuria in glomerulosclerosis rats and the protective effects of ATRA.
METHODS
This research set up three groups: SHO group, GS group, and ATRA group (15 mg/(kg d), Sigma, St. Louis, MO). The serum creatinine (Scr), urea nitrogen (BUN), and 24-h proteinuria were detected 12 weeks after administration of ATRA. The pathological and ultrastructure changes were observed under light microscope and transmission electron microscope. The protein expression of TGF-β and Col-IV in glomerulus was detected by immunohitochemistry method. The mRNA and the protein expression of glomerular TRPC6 were detected by RT-PCR and Western blot.
RESULTS
In the rat model of GS, the expressions of TRPC6 were significantly elevated compared with the normal rat group; however, the use of ATRA down-regulated the expression of TRPC6 in the glomeruli and attenuated glomerulosclerosis and proteinuria. Scr and BUN were also improved by the treatment of ATRA.
CONCLUSIONS
Our results demonstrated that ATRA could ameliorate glomerulosclerosis and proteinuria in GS, which may be related to suppressed expression of TRPC6.
目的
本研究旨在探讨肾小球硬化大鼠蛋白尿的分子机制及 ATRA 的保护作用。
方法
本研究设立三组：SHO 组、GS 组和 ATRA 组（15mg/（kg·d），Sigma，圣路易斯，密苏里州）。给药 12 周后检测血清肌酐（Scr）、尿素氮（BUN）和 24 小时尿蛋白。光镜和透射电镜观察病理和超微结构变化。免疫组织化学法检测肾小球 TGF-β和 Col-IV 蛋白表达。用 RT-PCR 和 Western blot 检测肾小球 TRPC6 的 mRNA 和蛋白表达。
结果
在 GS 大鼠模型中，TRPC6 的表达明显高于正常大鼠组；然而，ATRA 的使用下调了肾小球中 TRPC6 的表达，减轻了肾小球硬化和蛋白尿。ATRA 治疗还改善了 Scr 和 BUN。
结论
我们的结果表明，ATRA 可改善 GS 中的肾小球硬化和蛋白尿，这可能与抑制 TRPC6 的表达有关。
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