Pharmacy Department, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, China.
Medicine Department, Peking University First Hospital, Beijing 100034, China.
Aging (Albany NY). 2020 Nov 10;12(22):22744-22758. doi: 10.18632/aging.103902.
Acute kidney injury is one of the most common complications that occurs in septic shock. An effective therapeutic intervention is urgently needed. Geniposide has been reported to possess pleiotropic activities against different diseases. However, the effect of geniposide on sepsis-induced kidney injury is unexplored. Our study aims to illustrate the mitigative effects of geniposide on sepsis-induced kidney injury and its relevant mechanisms. Sepsis was induced in mice undergoing cecal ligation and puncture (CLP) surgery. Mice were intraperitoneally injected with geniposide (10, 20 and 40 mg/kg) for treatment. The results showed that geniposide ameliorated kidney injury and dysfunction in CLP-induced septic mice, accompanied by reduction of inflammatory response and oxidative stress. We also found that geniposide significantly reduced vascular permeability and cellular apoptosis of the kidney, with increase of Bcl-2 and decrease of Bax and cleaved caspase-3. Moreover, PPARγ was found to be upregulated with the increasing concentration of geniposide. The protection of geniposide against inflammation and apoptosis was recovered by inhibition of PPARγ. Collectively, these results indicate that geniposide could significantly ameliorate acute kidney injury in CLP-induced septic mice and LPS-stimulated HK-2 cells by activating PPARγ. Geniposide might be a potential drug candidate for sepsis-induced kidney injury.
急性肾损伤是脓毒症中最常见的并发症之一。迫切需要有效的治疗干预措施。栀子苷已被报道具有针对多种疾病的多种作用。然而，栀子苷对脓毒症引起的肾损伤的影响尚未得到探索。我们的研究旨在阐明栀子苷对脓毒症引起的肾损伤的缓解作用及其相关机制。通过盲肠结扎和穿刺（CLP）手术诱导小鼠发生脓毒症。用栀子苷（10、20 和 40mg/kg）对小鼠进行腹腔内注射治疗。结果表明，栀子苷改善了 CLP 诱导的脓毒症小鼠的肾损伤和功能障碍，同时减轻了炎症反应和氧化应激。我们还发现，栀子苷可显著降低肾脏的血管通透性和细胞凋亡，增加 Bcl-2 并减少 Bax 和 cleaved caspase-3。此外，随着栀子苷浓度的增加，PPARγ 被发现上调。通过抑制 PPARγ，栀子苷对炎症和细胞凋亡的保护作用得到恢复。总之，这些结果表明，栀子苷通过激活 PPARγ，可显著改善 CLP 诱导的脓毒症小鼠和 LPS 刺激的 HK-2 细胞中的急性肾损伤。栀子苷可能是治疗脓毒症引起的肾损伤的潜在药物候选物。
