在UUO大鼠中,levosimendan通过TGF-β1/Smad轴调节减轻纤维化
Rohan Bhadange1, Neha Dagar1, Anil Bhanudas Gaikwad1
1Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Pilani Campus, Vidya Vihar, Pilani, Rajasthan 333031, India.
概括
莱沃西门丹 (LVS) 通过减少纤维化和细胞外基质积累,显示出治疗慢性病 (CKD) 的潜力. 这项研究证明了LVS.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
背景情况:
- 慢性病 (CKD) 标志着纤维化,上皮 - 介质细胞过渡 (EMT) 和细胞外基质 (ECM) 积累,通常进展到末期病 (ESKD).
- 目前用于CKD的治疗方法往往是无效的,并且伴有不良影响.
- 利沃西门丹 (LVS) 是一种敏化剂和扩散剂,用于心力衰竭.
研究的目的:
- 调查Levosimendan (LVS) 在单边尿路阻塞 (UUO) 诱导的CKD的老鼠模型中的脏保护作用.
- 评估LVS对转化生长因子-β1 (TGF-β1) 诱导的纤维化在NRK-52E细胞中的影响.
- 阐明LVS在CKD中的抗纤维作用背后的分子机制.
主要方法:
- 雄性斯普拉格-道利大鼠接受了UUO手术,并接受了LVS (3 mg/kg) 或载体治疗21天.
- NRK-52E细胞被TGF-β1和LVS (10μM) 治疗了48小时,以在体外诱导纤维化.
- 分析包括血和尿液的生物化学,组织学,免疫组织化学,免疫血栓和细胞活力测定.
主要成果:
- 在UUO大鼠中,LVS治疗显著改善了功能标志物 (肌素,BUN,尿素) 并降低了TGF-β1和纤维素蛋白水平.
- 组织学检查显示,在接受LVS治疗的老鼠中,管道亡,血球硬化和管间纤维化减少.
- 在体内,LVS抑制了EMT标记物 (α-SMA,维丁),降低了p-Smad 2/3,并上调了E-cadherin,同时在体内调节了ECM组件和Smad信号.
结论:
- 在临床前的CKD模型中,Levosimendan (LVS) 有效抑制纤维化和EMT.
- LVS通过调节TGF-β1/Smad信号通路来发挥其脏保护作用.
- 这些发现表明LVS具有作为治疗慢性病管理的治疗剂的潜力.
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