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| Effect of inhibition of Rictor on myocardial autophagy in sepsis mice |
| JIANG Wanwei YANG Guohui |
| Clinical Medical School, Guizhou Medical University, Guizhou Province, Guiyang 550004, China |
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Abstract Objective To study the effect of inhibition Rictor on myocardial autophagy in sepsis mice. Methods A total of 36 healthy male SPF Kunming mice were divided into sham operation group, model group, and experimental group according to the random number table method, with 12 mice in each group. The animal model of sepsis was established by cecal ligation and puncture. The experimental group was given 10 mg/kg intraperitoneal injection of Rictor-specific inhibitor JR-AB2-011, the sham operation group and model group were given the same amount of normal saline. Abdominal aortic blood was collected from six mice in each group at 12 and 24 h postoperatively, and the levels of serum cardiac troponin I (cTnI) and creatine kinase MB (CK-MB) were detected. The expression changes of Rictor, Akt, Raptor, and LC3B in mouse myocardial tissue were detected; the pathological changes of myocardial tissue were observed by transmission electron microscope and HE staining. Results In model group, cTnI, CK-MB, Rictor, Phospho-Aktser473, and Raptor at each time point were higher than those in sham operation group (P < 0.05). In the experimental group, cTnI, CK-MB, Rictor, Phospho-Aktser473, and Raptor at each time point were lower than those in model group, and LC3B were higher than that in model group (P < 0.05). The myocardial fibers of the sham operation group was normal; moderate watery degeneration of myocardial fibers can be seen in model group; a small amount of myocardial fibers showed watery degeneration and cell swelling in experimental group. Autophagosomes and autophagy lysozyme could be observed in model group and experimental group. Conclusion Inhibition Rictor can enhance autophagy of myocardial cells in sepsis mice and reduce cell damage.
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[1] Cheng Mm W，Long Y，Wang H，et al. Role of the mTOR Signalling Pathway in Human Sepsis-Induced Myocardial Dysfunction [J]. Can J Cardiol，2019，35（7）：875-883.
[2] 黄建平，周杨青，刘海芬.构建脓毒症心肌抑制死亡的预警模型：附129例患者回顾性分析[J].中华危重病急救医学，2018，30（5）：461-465.
[3] 谢蓉蓉，谢剑锋，杨毅.脓毒症患者远期预后的现状及干预对策[J].中华内科杂志，2019，58（4）：329-332.
[4] 于涛，冯瑛，张丽丽，等.脓毒症心肌病发病机制的研究进展[J].医学综述，2021，27（17）：3363-3370.
[5] Napoletano F，Baron O，Vandenabeele P，et al. Intersections between Regulated Cell Death and Autophagy [J]. Trends in Cell Biology，2019，29（4）：323-338.
[6] 张欣桐，刘景卓，李盼，等.线粒体自噬在脓毒症中的研究进展[J].中国医药导报，2021，18（10）：39-42.
[7] Benavides-Serrato A，Lee J，Holmes B，et al. Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is cytotoxic in glioblastoma [J]. PLoS One，2017，12（4）：e0176599.
[8] Chen FC，Xu YC，Zhang ZC. Multi-biomarker strategy for prediction of myocardial dysfunction and mortality in sepsis [J]. J Zhejiang Univ Sci B，2020，21（7）：537-548.
[9] Morgan RW，Fitzgerald JC，Weiss SL，et al. Sepsis-associated in-hospital cardiac arrest：Epidemiology，pathophysiology，and potential therapies [J]. J Crit Care，2017，40：128-135.
[10] 余雷，孙荣青.脓毒症心功能障碍患者评估及治疗进展[J].中华危重病急救医学，2019（3）：378-380.
[11] Fenton KE，Parker MM. Cardiac Function and Dysfunction in Sepsis [J]. Clin Chest Med，2016，37（2）：289-298.
[12] Nabzdyk CS，Couture EJ，Shelton K，et al. Sepsis induced cardiomyopathy：Pathophysiology and use of mechanical circulatory support for refractory shock [J]. J Crit Care，2019，54：228-234.
[13] 王凤新，张博，白秀萍.脓毒症心肌损伤机制研究进展[J].内科急危重症杂志，2018，24（5）：437-440.
[14] 王天元.脓毒症患者心肌肌钙蛋白Ⅰ升高的危险因素研究[D].天津：天津医科大学，2020.
[15] Huang M，Cai S，Su J. The Pathogenesis of Sepsis and Potential Therapeutic Targets [J]. Int J Mol Sci，2019，20（21）：5376.
[16] 介希.氧化应激介导心力衰竭时病理性心肌细胞自噬的机制研究[D].太原：山西医科大学，2021.
[17] Kumar V. Dendritic cells in sepsis：Potential immunoregulatory cells with therapeutic potential [J]. Mol Immunol，2018，101：615-626.
[18] 尚秀玲.脓毒症心肌损伤的临床和基础研究[D].北京：北京协和医学院，2018.
[19] 胡晓青，慧美，沈璐妍，等.PI3K/AKT/mTOR信号通路与线粒体稳态在疾病治疗中的作用[J].中国病理生理杂志，2021，37（11）：2072-2076.
[20] 许银丰，汪倩，钱楚莹，等.mTORC1信号通路调控细胞自噬的研究进展[J].中国科学（生命科学），2022，52（2）：266-272.
[21] 黎李俊，杨国辉.雷帕霉素对脓毒症大鼠心肌自噬水平的影响[J].山东医药，2019，59（29）：37-39.
[22] Knudsen JR，Fritzen AM，James DE，et al. Growth Factor-Dependent and -Independent Activation of mTORC2 [J]. Trends Endocrinol Metab，2020，31（1）：13-24.
[23] Cheng Z. The FoxO-Autophagy Axis in Health and Disease [J]. Trends Endocrinol Metab，2019，30（9）：658-671.
[24] 张春晓，栾红，陈玉东，等.雷帕霉素调控PI3K-AKT-mTOR信号通路对心力衰竭大鼠心肌细胞凋亡的影响[J].中国慢性病预防与控制，2020，28（5）：371-374.
[25] 施诚龙，陈冲，高永军，等.PI3K/AKT/mTOR信号通路在细胞自噬中作用及机制的研究进展[J].山东医药，2021， 61（27）：102-105. |
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