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黄芪总皂苷通过促进线粒体合成和抑制细胞凋亡改善腹膜纤维化。

Astragalus Total Saponins Ameliorate Peritoneal Fibrosis by Promoting Mitochondrial Synthesis and Inhibiting Apoptosis.

机构信息

Department of Nephrology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P. R. China.

Department of Emergency Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, P. R. China.

出版信息

Am J Chin Med. 2022;50(1):261-274. doi: 10.1142/S0192415X22500094. Epub 2022 Jan 4.

DOI:10.1142/S0192415X22500094
PMID:34983328
Abstract

Peritoneal fibrosis (PF) is a disease caused by prolonged exposure of the peritoneum to high levels of dialysis fluid. Astragalus total saponins (ATS) is a phytochemical naturally occurring in that has anti-inflammatory and anti-oxidant properties. In this study, we constructed an model of PF using 4.25% glucose-containing administered intraperitoneally to rats and incubated peritoneal mesothelial cells (PMCs) with 4.25% glucose-containing peritoneal dialysis fluid to construct an model of PF. Furthermore, siRNA of PGC-1[Formula: see text] was used to inhibit the expression of PGC-1[Formula: see text] to further investigate the mechanism of the protective effect of ATS on PF. In both and models, ATS treatment showed a protective effect against PF, with ATS reducing the thickness of peritoneal tissues in PF rats, increasing the viability of PMCs, increasing the mitochondrial membrane potential and reducing apoptosis ratio. ATS treatment also reduced the expressions of peritoneal fibrosis markers (Smad2, p-Smad2 and [Formula: see text]-SMA) and apoptosis markers (Caspase3, cleaved-Caspase3 and Bax) and restored the expressions of mitochondrial synthesis proteins (PGC-1[Formula: see text], NRF1 and TFAM) in ATS-treated peritoneal tissues or PMCs. Furthermore, in the presence of PGC-1[Formula: see text] inhibition, the protective effect of ATS on PF was blocked. In conclusion, ATS treatment may be an effective therapeutic agent to inhibit high glucose-induced in peritoneal fibrosis through PGC-1[Formula: see text]-mediated apoptosis.

摘要

腹膜纤维化(PF)是一种由腹膜长时间暴露在高浓度透析液中引起的疾病。黄芪总皂苷(ATS)是一种天然存在于 的植物化学物质,具有抗炎和抗氧化特性。在本研究中,我们通过向大鼠腹腔内注射 4.25%葡萄糖含有的透析液构建 PF 模型,并将腹膜间皮细胞(PMCs)与 4.25%葡萄糖含有的腹膜透析液孵育构建 PF 模型。此外,使用 PGC-1[Formula: see text] 的 siRNA 抑制 PGC-1[Formula: see text] 的表达,进一步研究 ATS 对 PF 的保护作用机制。在 和 模型中,ATS 治疗均显示出对 PF 的保护作用,ATS 降低 PF 大鼠腹膜组织的厚度,增加 PMCs 的活力,增加线粒体膜电位,降低细胞凋亡率。ATS 治疗还降低了腹膜纤维化标志物(Smad2、p-Smad2 和 [Formula: see text]-SMA)和凋亡标志物(Caspase3、cleaved-Caspase3 和 Bax)的表达,并恢复了 ATS 处理的腹膜组织或 PMCs 中线粒体合成蛋白(PGC-1[Formula: see text]、NRF1 和 TFAM)的表达。此外,在 PGC-1[Formula: see text] 抑制存在的情况下,ATS 对 PF 的保护作用被阻断。总之,ATS 治疗可能是一种通过 PGC-1[Formula: see text] 介导的凋亡抑制高葡萄糖诱导的腹膜纤维化的有效治疗药物。