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β-石竹烯可能通过调节应激标志物KIM-1/MCP-1和NF-κB信号通路减轻大鼠高草酸尿症诱导的肾功能障碍。

β-Caryophyllene may attenuate hyperoxaluria-induced kidney dysfunction in rats by regulating stress marker KIM-1/MCP-1 and NF-κB signaling pathway.

作者信息

Xu Xia, Yan Jiamiao

机构信息

Department of Pharmacy, Ankang Hospital of Traditional Chinese Medicine, Ankang, China.

出版信息

J Biochem Mol Toxicol. 2021 Nov;35(11):e22891. doi: 10.1002/jbt.22891. Epub 2021 Aug 31.

DOI:10.1002/jbt.22891
PMID:34468068
Abstract

β-Caryophyllene (BCP), a bicyclic sesquiterpene, has proved to exhibit antioxidant and anti-inflammatory activities. The present study is carried out to investigate BCP impact on hyperoxaluria-induced kidney dysfunction in male Wistar rats. The animals were categorized into four groups, namely, Group I, control rats; Group II, ethylene glycol (inducer); Group III, inducer + BCP (100 µM/kg bw); Group IV, BCP alone. After the treatment period, the rate of creatinine clearance and the concentration of urea in urine and serum were assessed. Histopathology reports were conducted to study renal and liver tissues, while the reverse transcription-polymerase chain reaction studies were carried out for messenger RNA expression of inflammatory (nuclear factor kappa B) and endoplasmic reticulum (ER) stress (kidney dysfunction molecule-1, monocyte chemoattractant protein-1, glucose binding protein 78, CHOP, activating factor 4, and X-box binding protein-1) markers as well as antioxidant activity for the hyperoxaluric rats. Western blot was performed to investigate the level of protein expression by the treatment group on apoptotic (Bcl-2, Bax, caspase-3, and caspase-9) proteins. The results show BCP to possess a renoprotective effect under hyperoxaluric conditions by decreasing the level of the inflammatory and ER stress markers and restoring the enzymes' antioxidant activities. The histology reports depicted the satisfactory morphology of glomerulus in diseased rats. Furthermore, the results of Western blot suggested that BCP may possess inhibitory action on apoptosis by affecting the mitochondrial-dependent apoptotic pathway. Therefore, BCP can be considered as a potential candidate for the therapy of hyperoxaluric-induced kidney complications.

摘要

β-石竹烯(BCP)是一种双环倍半萜烯,已被证明具有抗氧化和抗炎活性。本研究旨在探讨BCP对雄性Wistar大鼠高草酸尿症诱导的肾功能障碍的影响。动物被分为四组,即第一组,对照大鼠;第二组,乙二醇(诱导剂);第三组,诱导剂 + BCP(100 μM/kg体重);第四组,单独使用BCP。治疗期结束后,评估肌酐清除率以及尿液和血清中尿素的浓度。进行组织病理学报告以研究肾脏和肝脏组织,同时对高草酸尿症大鼠进行炎症(核因子κB)和内质网(ER)应激(肾功能障碍分子-1、单核细胞趋化蛋白-1、葡萄糖结合蛋白78、CHOP、激活因子4和X盒结合蛋白-1)标志物的信使核糖核酸表达以及抗氧化活性的逆转录-聚合酶链反应研究。进行蛋白质印迹法以研究治疗组对凋亡(Bcl-2、Bax、半胱天冬酶-3和半胱天冬酶-9)蛋白的蛋白质表达水平。结果表明,BCP在高草酸尿症条件下具有肾脏保护作用,可通过降低炎症和ER应激标志物水平并恢复酶的抗氧化活性来实现。组织学报告显示患病大鼠肾小球形态良好。此外,蛋白质印迹结果表明,BCP可能通过影响线粒体依赖性凋亡途径对凋亡具有抑制作用。因此,BCP可被视为治疗高草酸尿症诱导的肾脏并发症的潜在候选药物。

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