雷帕霉素通过雷帕霉素机制靶标(mTOR)信号通路减轻瓦斯爆炸诱发的大鼠脾脏损伤

IF 3.7 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Biochemical Engineering Journal Pub Date : 2024-07-24 DOI:10.1016/j.bej.2024.109436
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引用次数: 0

摘要

瓦斯爆炸是煤矿开采中经常发生的事件,其冲击波会造成严重的脾脏损伤,目前尚无有效的治疗方法。本研究旨在探讨自噬在瓦斯爆炸诱发的大鼠爆炸性脾损伤中的调控作用。将120只Sprague-Dawley雄性大鼠随机分为4组,包括正常对照组(NC)、瓦斯爆炸诱发脾脏损伤组(Model,M)、自噬抑制剂3-甲基腺嘌呤组(M+3-MA)和诱导雷帕霉素组(RAPA)(M+RAPA)。爆炸后,抑制剂组和诱导组大鼠立即腹腔注射 3-MA(15 毫克/千克)/RAPA(1 毫克/千克)。大鼠被麻醉后,分别于 24 小时、72 小时和 7 天后取脾脏。结果表明,气爆可降低大鼠的脾脏指数,诱导脾脏充血、炎症细胞浸润和自噬体增加。模型组Lc3-Ⅱ表达增加,p62和p-mTOR表达显著下降(P<0.05)。与模型组相比,RAPA能明显改善脾指数、脾出血、炎症和自噬体。Lc3-Ⅱ的表达明显增加,p62和p-mTOR的表达明显减少,而抑制剂组的结果恰恰相反。综上所述,我们首次发现 RAPA 可通过 mTOR 信号转导缓解瓦斯爆炸诱导的脾脏损伤,为治疗包括但不限于煤矿事故的脾脏损伤提供了新思路。
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Rapamycin mitigates gas explosion-induced spleen injury in rats via mechanistic target of rapamycin (mTOR) signaling pathway

Gas explosion is a recurrent event in coal mining that cause severe spleen damage due to shockwaves, which has no effective treatment. This study aimed to explore the regulatory role of autophagy in gas explosion-induced blast spleen injuries in rats. 120 Sprague-Dawley male rats were randomly divided into 4 groups, including normal control (NC), gas explosion-induced spleen injury (Model, M), autophagy inhibitor 3-methyladenine group (M+3-MA), and induction Rapamycin (RAPA) group (M+RAPA) groups. After explosion, the inhibitor group and induction group rats were immediately given intraperitoneal injection of 3-MA (15 mg/kg)/ RAPA (1 mg/kg). The rats were anesthetized and the spleen were obtained at 24 h, 72 h, and 7 days. The results showed that gas explosion reduced the spleen index, induced spleen blooding, infiltration of inflammatory cells, and increased autophagosomes. The expression of Lc3-Ⅱ was increased, whereas p62 and p-mTOR was decreased significantly (P<0.05) in model group. Compared with the model group, RAPA improved the spleen index, spleen bleeding, inflammation, and autophagosomes significantly. The expression of Lc3-Ⅱ was increased, p62 and p-mTOR was decreased significantly, but the opposite results were observed in the inhibitor group. Taken together, we firstly found that RAPA can mitigate gas explosion-induced spleen injury via mTOR signaling, which provides a new idea for the treatment of spleen injury including but not limited to coal mine accidents.

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来源期刊
Biochemical Engineering Journal
Biochemical Engineering Journal 工程技术-工程:化工
CiteScore
7.10
自引率
5.10%
发文量
380
审稿时长
34 days
期刊介绍: The Biochemical Engineering Journal aims to promote progress in the crucial chemical engineering aspects of the development of biological processes associated with everything from raw materials preparation to product recovery relevant to industries as diverse as medical/healthcare, industrial biotechnology, and environmental biotechnology. The Journal welcomes full length original research papers, short communications, and review papers* in the following research fields: Biocatalysis (enzyme or microbial) and biotransformations, including immobilized biocatalyst preparation and kinetics Biosensors and Biodevices including biofabrication and novel fuel cell development Bioseparations including scale-up and protein refolding/renaturation Environmental Bioengineering including bioconversion, bioremediation, and microbial fuel cells Bioreactor Systems including characterization, optimization and scale-up Bioresources and Biorefinery Engineering including biomass conversion, biofuels, bioenergy, and optimization Industrial Biotechnology including specialty chemicals, platform chemicals and neutraceuticals Biomaterials and Tissue Engineering including bioartificial organs, cell encapsulation, and controlled release Cell Culture Engineering (plant, animal or insect cells) including viral vectors, monoclonal antibodies, recombinant proteins, vaccines, and secondary metabolites Cell Therapies and Stem Cells including pluripotent, mesenchymal and hematopoietic stem cells; immunotherapies; tissue-specific differentiation; and cryopreservation Metabolic Engineering, Systems and Synthetic Biology including OMICS, bioinformatics, in silico biology, and metabolic flux analysis Protein Engineering including enzyme engineering and directed evolution.
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