贝母辛通过抑制JAK/STAT通路减轻炎症和铁死亡，从而改善糖尿病肾病
Peimisine ameliorates diabetic nephropathy by attenuating inflammation and ferroptosis through inhibition of the JAK/STAT pathway.
摘要(中文译文)
本研究旨在探讨贝母素甲对糖尿病肾病(DN)的影响，并在高脂饮食和链脲佐菌素诱导的DN小鼠模型及高糖(HG)处理的MPC5细胞模型中探索其潜在机制。通过测定体重、空腹血糖、血浆总胆固醇、血浆甘油三酯、血清肌酐、血尿素氮、病理变化、氧化应激标志物、炎症细胞因子和铁死亡相关指标，分析贝母素甲对DN小鼠的有益作用。此外，采用CCK-8实验、流式细胞术、炎症细胞因子检测、线粒体膜电位(MMP)检测、DCFH-DA探针、BODIPY 581/591 C11探针、氧化应激标志物和铁死亡相关指标检测，评估贝母素甲对HG处理的MPC5细胞的有益作用。采用qRT-PCR和蛋白质印迹法测定Janus激酶-信号转导子和转录激活子(JAK-STAT)通路相关基因的表达。通过使用RO8191(JAK激活剂)进行 rescue 实验，进一步探讨潜在机制。我们发现贝母素甲可改善DN小鼠的代谢功能障碍以及肾功能和结构损伤。此外，贝母素甲可改善DN小鼠的炎症和铁死亡。同样，贝母素甲也被证明可改善HG处理的MPC5细胞中的炎症和铁死亡。在机制上，贝母素甲在体外和体内均可抑制JAK/STAT通路。贝母素甲对HG处理的MPC5细胞中炎症和铁死亡的抑制作用可被RO8191逆转。我们的研究结果表明，贝母素甲通过抑制JAK/STAT信号通路来减轻炎症反应和铁死亡，从而改善DN。
Abstract
This study aimed to investigate the effect of peimisine on diabetic nephropathy (DN) and explore its potential mechanisms in a mouse model of high-fat diet and streptozocin-induced DN and cell model of high glucose (HG)-treated MPC5 cells. The beneficial effects of peimisine in DN mice were analyzed via determining body weight, fasting blood glucose, plasma total cholesterol, plasma triglyceride, serum creatinine, blood urea nitrogen, pathological changes, oxidative stress markers, inflammatory cytokines, and ferroptosis-related indicators. Furthermore, CCK-8 assay, flow cytometry, inflammatory cytokines, mitochondrial membrane potential (MMP) detection, DCFH-DA probe, BODIPY 581/591 C11 probe, oxidative stress markers, and ferroptosis-related indicators were conducted to measure the beneficial effects of peimisine on HG-treated MPC5 cells. qRT-PCR and western blotting were employed for determining Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway-associated genes expression. The potential mechanism was further investigated through rescue experiments using RO8191 (a JAK activator). We discovered that peimisine could ameliorate metabolic dysfunction, and the impairment of renal function and structure in DN mice. Moreover, peimisine could ameliorate inflammation and ferroptosis in DN mice. Similarly, peimisine was also demonstrated to ameliorate inflammation and ferroptosis in HG-treated MPC5 cells. Mechanistically, peimisine could inhibit the JAK/STAT pathway in vitro and in vivo. The inhibitory effects of peimisine on inflammation and ferroptosis in HG-treated MPC5 cells were reversed by RO8191. Our findings demonstrated that peimisine could ameliorate DN by attenuating inflammatory responses and ferroptosis through inhibition of the JAK/STAT signaling.
如何引用
AMA
Junsheng Qu, Shihua Wang, Jie Wang, Dehong Fan, Xue Liu, Xuan Zhang, et al. Peimisine ameliorates diabetic nephropathy by attenuating inflammation and ferroptosis through inhibition of the JAK/STAT pathway.. Experimental cell research. 2026; doi:10.1016/j.yexcr.2026.115125.
APA
Junsheng Qu, Shihua Wang, Jie Wang, Dehong Fan, Xue Liu, Xuan Zhang, et al (2026). Peimisine ameliorates diabetic nephropathy by attenuating inflammation and ferroptosis through inhibition of the JAK/STAT pathway.. Experimental cell research. https://doi.org/10.1016/j.yexcr.2026.115125
GB/T 7714
Junsheng Qu, Shihua Wang, Jie Wang, Dehong Fan, Xue Liu, Xuan Zhang, et al. Peimisine ameliorates diabetic nephropathy by attenuating inflammation and ferroptosis through inhibition of the JAK/STAT pathway.[J]. Experimental cell research, 2026 doi:10.1016/j.yexcr.2026.115125.
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