PDF(Pubmed)
Abstract：
The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI). Ganoderma lucidum polysaccharides (GLPs) exhibit hepatoprotective activity, yet the protective impact and potential mechanism of GLPs in relation to APAP-induced ALI remain ambiguous. The intention of this research was to scrutinize the effect of GLPs on APAP-induced ALI and to shed light on their potential mechanism. The results demonstrated that GLPs were capable of notably alleviating the oxidative stress triggered by APAP, as shown through a significant drop in the liver index, the activities of serum ALT and AST, and the amounts of ROS and MDA in liver tissue, along with an increase in the levels of SOD, GSH, and GSH-Px. Within these, the hepatoprotective activity at the high dose was the most conspicuous, and its therapeutic efficacy surpassed that of the positive drug (bifendate). The results of histopathological staining (HE) and apoptosis staining (TUNEL) indicated that GLPs could remarkably inhibit the necrosis of hepatocytes, the permeation of inflammatory cells, and the occurrence of apoptosis induced by APAP. Moreover, Western blot analysis manifested that GLPs enhanced the manifestation of Nrf2 and its subsequent HO-1, GCLC, and NQO1 proteins within the Nrf2 pathway. The results of qPCR also indicated that GLPs augmented the expression of antioxidant genes Nrf2, HO-1, GCLC, and NQO1. The results reveal that GLPs are able to set off the Nrf2 signaling path and attenuate ALI-related oxidative stress and apoptosis, which is a potential natural medicine for the therapy of APAP-induced liver injury.
摘要：
对乙酰氨基酚（APAP）的过度使用能够产生氧化应激和细胞凋亡，最终导致急性肝损伤（ALI）。灵芝多糖（GLPs）具有保肝活性，然而,GLPs对APAP诱导的ALI的保护作用和潜在机制仍不明确.这项研究的目的是仔细检查GLPs对APAP诱导的ALI的影响，并阐明其潜在机制。结果表明，GLPs能够显著减轻APAP引发的氧化应激，如肝脏指数显著下降所示，血清ALT和AST的活性，以及肝组织中ROS和MDA的含量，随着SOD水平的增加，GSH,和GSH-Px。在这些之内,高剂量的肝保护活性是最明显的，其治疗效果超过了阳性药物（分叉）。组织病理学染色（HE）和细胞凋亡染色（TUNEL）结果表明，GLPs能显著抑制肝细胞坏死，炎症细胞的渗透，APAP诱导细胞凋亡的发生。此外，Westernblot分析表明，GLPs增强了Nrf2及其随后的HO-1，GCLC的表现，和Nrf2途径内的NQO1蛋白。qPCR的结果还表明GLPs增强了抗氧化基因Nrf2，HO-1，GCLC，NQO1。结果表明，GLPs能够启动Nrf2信号通路，减轻ALI相关的氧化应激和凋亡，是治疗APAP引起的肝损伤的潜在天然药物。
