南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (10): 1399-1405.doi: 10.12122/j.issn.1673-4254.2020.10.04

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牛蒡子苷通过抑制炎症通路降低雷公藤甲素所致肾毒性

周玉燕，陆萧雅，夏 丽，姚伟强，秦国正，王国栋   

  • 出版日期:2020-10-20 发布日期:2020-10-20

Arctiin antagonizes triptolide-induced renal toxicity in rats via anti-inflammatory pathway

  • Online:2020-10-20 Published:2020-10-20

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摘要： 目的 探讨具有抗炎活性的牛蒡子苷对雷公藤甲素（TP）所致的大鼠肾毒性的保护作用和潜在机制。方法 将40只SD大鼠随机分为4组：对照组（不含药液的PBS），牛蒡子苷组（500 mg· kg-1· d-1），雷公藤甲素组（500 μg· kg-1· d-1），联合用药组（牛蒡子苷500 mg· kg-1· d-1+雷公藤甲素500 μg· kg-1· d-1）。分别予以相应处理后，采血测定肾脏生化指标，取肾脏测定肾脏指数并用HE染色观察其组织病理学变化。进一步体外培养人肾小管上皮细胞（HK-2细胞），MTT法检测细胞的存活率变化，激光共聚焦显微镜记录各组细胞的形态变化，流式细胞术测定细胞凋亡率改变，Western blot法检测炎症相关通路蛋白表达变化。结果 在体内实验中，牛蒡子苷显著降低了TP所致的大鼠血清尿素氮（BUN），肌酐（Scr）等肾脏生化指标和肾脏指数（P<0.05）。此外，牛蒡子苷明显改善了TP所致的肾细胞的水肿，空泡化和点状坏死等组织病理学改变。在体外实验中，牛蒡子苷抑制了TP诱导的HK-2细胞毒性，24 h细胞存活率明显升高（P<0.05）；改善了凋亡的细胞形态，细胞凋亡率显著下降（P<0.05）；逆转了炎性通路中IκBα和Nuclear p65蛋白表达（P<0.05）。结论 牛蒡子苷可以减轻雷公藤甲素所致的肾损害，其机制可能与其抗炎活性有关。

关键词: 牛蒡子苷, 雷公藤甲素, 肾损伤, 抗炎通路

Abstract: Objective To investigate the protective effect of arctiin with anti-inflammatory bioactivity against triptolide-induced nephrotoxicity in rats and explore the underlying mechanism. Methods Forty SD rats were divided into 4 groups for gastric lavage of normal saline, arctiin (500 mg/kg), triptolide (500 μg/kg), or both arctiin (500 mg/kg) and triptolide (500 μg/kg). Blood samples were collected for analysis of biochemical renal parameters, and the renal tissues were harvested for determining the kidney index and for pathological evaluation with HE staining. In the in vitro experiment, HK-2 cells were treated with arctiin and triptolide either alone or in combination, and the cell viability was determined with MTT assay; the cell morphological changes was observed using laser confocal microscopy, cell apoptosis was detected using flow cytometry, and the expressions of inflammation-related protein expression were detected by Western blotting. Results In SD rats, arctiin significantly antagonized triptolide-induced elevation of BUN, Scr and kidney index (P<0.05) and obviously improved renal tissue damages induced by triptolide including cell swelling, vacuolization and spotty necrosis. Arctiin significantly inhibited triptolide-induced cytotoxicity in HK-2 cells and increased the cell viability at 24 h (P<0.05). Arctiin also attenuated triptolide-induced cell morphological changes, decreased cell apoptosis rate (P<0.05) and reversed the expressions of IκBα and nuclear p65 (P<0.05). Conclusion Arctiin can protect the kidney from triptolide-induced damages in rats possibly through the anti-inflammatory pathway.

Key words: arctiin, triptolide, renal injury, anti-inflammatory pathway