实验动物与比较医学2026，Vol.46Issue(2)：205-211,7.DOI:10.12300/j.issn.1674-5817.2025.092
溶质载体家族7成员5抑制剂JPH203对单侧输尿管梗阻诱导小鼠肾纤维化的抑制作用
Inhibitory Effect of Solute Carrier Family 7 Member 5 Inhibitor JPH203 on Renal Fibrosis Induced by Unilateral Ureteral Obstruction in Mice
崔畅婉 1路一平 1于淼 1王爽 1吴思 1孙峥嵘1
作者信息
- 1. 中国医科大学附属盛京医院人类遗传资源库,沈阳 110001
- 折叠
摘要
Abstract
Objective To investigate the effect of solute carrier family 7 member 5(SLC7A5)inhibitor JPH203 on renal fibrosis induced by unilateral ureteral obstruction in mice.Methods Sixteen SPF male C57BL/6 mice were randomly divided into the control group and the experimental group,with 8 mice in each group.The mouse model of renal fibrosis was established by unilateral ureteral obstruction.From the third day after surgery,the mice in the control group were intraperitoneally injected with phosphate-buffered saline(PBS)for 11 consecutive days,and the injection dose was 200 μL/d.Mice in the experimental group received intraperitoneal injection of JPH203(50 mg/kg)every day for 11 days.On day 14,the mice were euthanized,then the kidney tissues were obtained.Hematoxylin and eosin(HE)staining was used to assess renal tissue damage,Masson staining was used to evaluate collagen fiber deposition in the extracellular matrix,and immunohistochemistry was used to detect the levels of fibroblast activation markers α-smooth muscle actin(α-SMA)and collagen type Ⅰ(COL-Ⅰ)in kidney tissues.Western blotting was further performed to measure the expression levels of SLC7A5 and transforming growth factor-β1(TGF-β1),as well as the phosphorylation levels of mammalian target of rapamycin complex 1(mTORC1)signaling pathway-related molecules.Real-time quantitative PCR was used to verify changes in the mRNA levels of SLC7A5,α-SMA,and COL-Ⅰ in kidney tissues.Results Compared with the control group,the experimental group showed reduced destruction of renal tissue structure and a significantly lower pathological injury score(P＜0.05).Additionally,collagen deposition in the extracellular matrix was decreased,and the percentage of collagen fiber area was significantly reduced(P＜0.001)in the experimental group.The levels of fibroblast activation markers α-SMA and COL-Ⅰ were significantly lower in the experimental group(both P＜0.001).The expression levels of SLC7A5 and TGF-β1 were also significantly decreased(P＜0.001),and the phosphorylation levels of mTORC1 signaling pathway-related proteins 4E-BP1 and mTORC1 were significantly reduced(P＜0.001).Real-time quantitative PCR confirmed that the mRNA levels of SLC7A5,α-SMA,and COL-Ⅰ in kidney tissues were significantly lower in the experimental group(P＜0.001).Conclusion JPH203 may inhibit the progression of renal fibrosis in mice by suppressing SLC7A5 expression,regulating the mTORC1 signaling pathway,and altering fibroblast activation status.关键词
溶质载体家族7成员5抑制剂/JPH203/哺乳动物雷帕霉素靶蛋白复合物1/肾纤维化/单侧输尿管梗阻模型/小鼠Key words
Solute carrier family 7 member 5 inhibitor/JPH203/Mammalian target of rapamycin complex 1/Renal fibrosis/Unilateral ureteral obstruction model/Mice分类
生物科学引用本文复制引用
崔畅婉,路一平,于淼,王爽,吴思,孙峥嵘..溶质载体家族7成员5抑制剂JPH203对单侧输尿管梗阻诱导小鼠肾纤维化的抑制作用[J].实验动物与比较医学,2026,46(2):205-211,7.
