Astragalus Total Saponins Ameliorate Peritoneal Fibrosis by Promoting Mitochondrial Synthesis and Inhibiting Apoptosis
Astragalus Total Saponins Ameliorate Peritoneal Fibrosis by Promoting Mitochondrial Synthesis and Inhibiting Apoptosis
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DOI：
10.1142/s0192415x22500094
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发表时间：
2022-01-01
影响因子：
5.7
通讯作者：
Sheng, Mei-Xiao
中科院分区：
文献类型：
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作者：
Li, Zheng-Hong;Xu, Rong;Sheng, Mei-Xiao
腹膜纤维化（PF）是一种因腹膜长期暴露于高浓度透析液而引起的疾病。黄芪总皂苷 (ATS) 是黄芪中天然存在的一种植物化学物质，具有抗炎和抗氧化特性。本研究采用大鼠腹腔注射4.25%葡萄糖构建PF体内模型，并用含4.25%葡萄糖的腹膜透析液培养腹膜间皮细胞（PMC），构建PF体外模型。此外，利用PGC-1α的siRNA抑制PGC-1α的表达，进一步探讨ATS对PF的保护作用机制。在体内和体外模型中，ATS治疗均显示出对PF的保护作用，ATS减少了PF大鼠腹膜组织的厚度，增加了PMC的活力，增加了线粒体膜电位并降低了凋亡率。 ATS治疗还降低了ATS处理的腹膜组织或PMC中腹膜纤维化标志物（Smad2、p-Smad2和α-SMA）和凋亡标志物（Caspase3、cleaved-Caspase3和Bax）的表达，并恢复了线粒体合成蛋白（PGC-1α、NRF1和TFAM）的表达。此外，在存在 PGC-1 α 抑制的情况下，ATS 对 PF 的保护作用被阻断。总之，ATS 治疗可能是通过 PGC-1 α 介导的细胞凋亡抑制高糖诱导的腹膜纤维化的有效治疗剂。
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 Radix Astragali that has anti-inflammatory and anti-oxidant properties. In this study, we constructed an in vivo 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 in vitro model of PF. Furthermore, siRNA of PGC-1 alpha was used to inhibit the expression of PGC-1 alpha to further investigate the mechanism of the protective effect of ATS on PF. In both in vivo and in vitro 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 alpha-SMA) and apoptosis markers (Caspase3, cleaved-Caspase3 and Bax) and restored the expressions of mitochondrial synthesis proteins (PGC-1 alpha, NRF1 and TFAM) in ATS-treated peritoneal tissues or PMCs. Furthermore, in the presence of PGC-1 alpha 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 alpha-mediated apoptosis.