Albiflorin通过PI3K/AKT/NF-κB通路改善系膜增生性肾小球肾炎。

IF 2.7 4区 医学 Q3 TOXICOLOGY Human & Experimental Toxicology Pub Date : 2023-01-01 DOI:10.1177/09603271221145386
Haiyan Yu, Yu Wang, Zida He, Ruixue Chen, Yingni Dai, Yingqian Tang, Ye Chen
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引用次数: 1

摘要

背景:肾小球肾炎在中国最常见的类型是系膜增生性肾小球肾炎(MPGN),以系膜细胞过度增生、炎症和纤维化为特征。芍药苷(Albiflorin, AF)是从白芍中提取的一种有效成分,已被用于治疗多种疾病。然而,尚无研究报道AF对MPGN的影响。目的:探讨AF在MPGN中的作用及其可能的机制。研究设计:我们在体外和体内研究了AF对系膜细胞过度增殖、炎症和纤维化的影响,并确定了相关信号通路。研究样本:人系膜细胞(HMCs)和雄性SD大鼠。数据分析:采用SPSS 18.0软件对数据进行分析。结果:AF对小鼠体外和体内的增殖和炎症均有抑制作用。在脂多糖(LPS)处理的hmc和MPGN大鼠中,AF降低了ki67的表达,并降低了炎症因子的mRNA表达或含量。AF对lps处理的HMCs和MPGN大鼠的纤维化也有一定的抑制作用。AF能有效抑制24 h尿蛋白,改善肾功能,减轻MPGN大鼠的血脂异常和病理性损伤。此外,我们发现AF的保护作用伴随着PI3K/AKT/NF-κB通路的阻断,并且AF对MPGN的抑制作用被PI3K激动剂胰岛素样生长因子(IGF-1)逆转。结论:AF通过PI3K/AKT/NF-κB信号通路抑制肾小球系膜细胞过度增殖、炎症和纤维化,从而减轻MPGN。
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Albiflorin ameliorates mesangial proliferative glomerulonephritis by PI3K/AKT/NF-κB pathway.

Background: The most common type of glomerulonephritis in China is mesangial proliferative glomerulonephritis (MPGN) featured with mesangial cell overproliferation and inflammation, as well as fibrosis. Albiflorin (AF) is an effective composition extracted from Paeonia Alba Radix and has been administrated for various diseases. Nevertheless, there is no research reporting the effect of AF on MPGN.Purpose: Our work aims to probe into the role and possible mechanism of AF on MPGN.Research Design: We investigated the effects of AF on mesangial cell overproliferation, inflammation, and fibrosis in vitro and in vivo and identified the related signaling pathways.Study Sample: human mesangial cells (HMCs) and male Sprague Dawley (SD) rats.Data Analysis: SPSS 18.0 was used to analyze the data.Results: AF attenuated the proliferation and inflammation both in vitro and in vivo. In detail, AF decreased the ki67 expression in lipopolysaccharides (LPS)-treated HMCs and MPGN rats, and the mRNA expression or contents of inflammatory cytokines were reduced after AF treatment. The fibrosis of LPS-treated HMCs and MPGN rats was also reduced by AF. Moreover, AF effectively restrained 24 h urinary protein, improved kidney function, and mitigated dyslipidemia and pathological injury of MPGN rats. Additionally, we found that the protective effects of AF were accompanied by the blocking of PI3K/AKT/NF-κB pathway, and the inhibitory effects of AF on MPGN were reversed by insulin-like growth factor (IGF-1), the PI3K agonist.Conclusions: AF alleviates MPGN via restraining mesangial cell overproliferation, inflammation, and fibrosis via PI3K/AKT/NF-κB signaling.

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来源期刊
CiteScore
5.70
自引率
3.60%
发文量
128
审稿时长
2.3 months
期刊介绍: Human and Experimental Toxicology (HET), an international peer reviewed journal, is dedicated to publishing preclinical and clinical original research papers and in-depth reviews that comprehensively cover studies of functional, biochemical and structural disorders in toxicology. The principal aim of the HET is to publish timely high impact hypothesis driven scholarly work with an international scope. The journal publishes on: Structural, functional, biochemical, and molecular effects of toxic agents; Studies that address mechanisms/modes of toxicity; Safety evaluation of novel chemical, biotechnologically-derived products, and nanomaterials for human health assessment including statistical and mechanism-based approaches; Novel methods or approaches to research on animal and human tissues (medical and veterinary patients) investigating functional, biochemical and structural disorder; in vitro techniques, particularly those supporting alternative methods
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