原花青素通过抑制PPARα/PGC1α信号通路,抑制自噬和凋亡,缓解肝缺血/再灌注损伤。
Proanthocyanidin Alleviates Liver Ischemia/Reperfusion Injury by Suppressing Autophagy and Apoptosis via the PPARα/PGC1α Signaling Pathway.
发表日期:2023 Nov 28
作者:
Zhilu Yao, Ning Liu, Hui Lin, Yingqun Zhou
来源:
ANTIOXIDANTS & REDOX SIGNALING
摘要:
肝脏缺血再灌注损伤(IRI)是临床实践中常见的病理生理现象,通常发生在肝移植、肝切除、严重外伤和大出血休克中。我们的研究中给予来自多种植物的前花青素(PC),其具有抗氧化、抗肿瘤和抗衰老活性,以研究其对IRI保护功能的潜在机制。我们给予BALB/c小鼠两种剂量的PC(50 mg/kg、100 mg/kg)在温暖部分(70%)IR手术前通过胃管给药连续7天。再灌注后2、8和24小时采集血清和肝组织进行相关实验。转氨酶和苏木精-伊红染色的结果表明,PC预处理显著减轻了小鼠的IRI。PC预处理组血清总超氧化物歧化酶增加,丙二醛减少。酶联免疫吸附试验、蛋白免疫印迹、定量实时聚合酶链反应和免疫组织化学结果显示,PC预处理组中的炎症、细胞凋亡和自噬显著受到抑制,并且剂量依赖性。前花青素预处理组中过氧化物酶体增殖物激活受体α(PPARα)和过氧化物酶体增殖物激活因子1-α(PGC1α)的蛋白质、mRNA表达和免疫组织化学染色结果与IR组相比显著上调,且呈剂量依赖性。前花青素预处理通过PPAR-α信号通路抑制炎症、细胞凋亡和自噬,保护小鼠肝脏免受IRI的影响。© 2023 作者。
Hepatic ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon in clinical practice, which usually occurs in liver transplantation, liver resection, severe trauma, and hemorrhagic shock. Proanthocyanidin (PC), exerted from various plants with antioxidant, antitumor, and antiaging activity, were administrated in our study to investigate the underlying mechanism of its protective function on IRI.Two doses of PC (50 mg/kg, 100 mg/kg) were given to BALB/c mice by intragastric administration for 7 days before partial (70%) warm IR surgery. Serum and liver tissues were collected 2, 8, and 24 h after reperfusion for relevant experiments.The results of transaminase and hematoxylin and eosin staining indicated that PC pretreatment significantly alleviated IRI in mice. Serum total superoxide dismutase increased and malondialdehyde decreased in PC pretreatment groups. Enzyme-linked immunosorbent assays, western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry showed that inflammation, apoptosis, and autophagy in PC preprocessing groups were significantly inhibited and were dose-dependent. The protein, mRNA expression, and immunohistochemical staining results of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in the PC pretreatment groups were significantly upregulated compared with the IR group in a dose-dependent manner.PC pretreatment suppressed inflammation, apoptosis, and autophagy via the PPAR-α signaling pathway to protect against IRI of the liver in mice.© 2023 Authors.