Organ Transplantation Center, The First Affiliated Hospital, Kunming Medical University, Kunming, China.
Organ Transplantation Center, The First Affiliated Hospital, Kunming Medical University, Kunming, China.
Biomed Pharmacother. 2020 Sep;129:110398. doi: 10.1016/j.biopha.2020.110398. Epub 2020 Jun 27.
Hepatic ischemia reperfusion (I/R) injury (HIRI) HIRI is a complex, multifactorial pathophysiological process and in liver surgery has been known to significantly affect disease prognosis, surgical success rates, and patient survival. Ginsenoside Rgl (Rgl) monomer is one of the main active ingredients of ginseng. Previous studies have demonstrated that Rgl exerts various pharmacological effects through several mechanisms including suppression of apoptosis-related proteins levels, downregulation of inflammatory mediators and as well as antioxidant, which effectively exerts an organ protective effect I/R-induced damage. However, the exact mechanisms of Rg1 on HIRI remain to be elucidated. In the present study, we investigated the protective effect of Rg1 on hepatic ischemia-reperfusion (I/R) injury (HIRI) and explored its underlying molecular mechanism. A rat warm I/R injury model in vivo and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated BRL-3A cell model in vitro were established after pretreating with Rg1(20 mg/kg). The results showed that Rg1 reduced the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TUNEL staining showed that pretreated with Rg1 inhibited the apoptosis rate compared with the I/R group. Moreover, pretreated with Rg1 significantly reduced the expression of Cyt-C, Caspase-9 and Caspase-3 to inhibit the cell apoptosis. Flow cytometry analysis showed the MMP in the I/R group was significantly increased, whereas pretreated with Rg1 effectively stabilized the MMP compared with the I/R group. in vitro, the proliferation of BRL-3A cells was significantly decreased by the OGD/R treatment, while Rg1 effectively reversed this phenomenon. In addition, western blotting showed that the increase of Cyt-C, Caspase-9 and Caspase-3 was inhibited by HO. These observations suggest that Rg1 exerts the protective effect by inhibiting the CypD protein-mediated mitochondrial apoptotic pathway.
肝缺血再灌注（I/R）损伤（HIRI）是一个复杂的、多因素的病理生理过程，在肝外科中已被证实显著影响疾病预后、手术成功率和患者生存率。人参皂苷 Rgl（Rgl）单体是人参的主要活性成分之一。先前的研究表明，Rgl 通过几种机制发挥各种药理作用，包括抑制凋亡相关蛋白水平、下调炎症介质以及抗氧化作用，从而有效发挥对 I/R 诱导损伤的器官保护作用。然而，Rg1 对 HIRI 的确切机制仍有待阐明。在本研究中，我们研究了 Rg1 对肝缺血再灌注（I/R）损伤（HIRI）的保护作用，并探讨了其潜在的分子机制。在体内采用大鼠热缺血再灌注损伤模型，体外采用氧葡萄糖剥夺/再灌注（OGD/R）处理 BRL-3A 细胞模型，用 Rg1（20mg/kg）预处理。结果表明，Rg1 降低了丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的水平。TUNEL 染色显示，与 I/R 组相比，Rg1 预处理抑制了细胞凋亡率。此外，Rg1 预处理显著降低 Cyt-C、Caspase-9 和 Caspase-3 的表达，从而抑制细胞凋亡。流式细胞术分析显示，I/R 组的 MMP 明显增加，而 Rg1 预处理可有效稳定 MMP 与 I/R 组相比。在体外，OGD/R 处理可显著降低 BRL-3A 细胞的增殖，而 Rg1 可有效逆转这种现象。此外，Western blot 显示，HO 抑制了 Cyt-C、Caspase-9 和 Caspase-3 的增加。这些观察结果表明，Rg1 通过抑制 CypD 蛋白介导的线粒体凋亡途径发挥保护作用。
