【摘 要】
：
Background and Aims: Reducing reactive oxygen species (ROS) production has proven an effective way for allevi-ating oxidative stress during ischemia-reperfusion injury (IRI). Moreover, inhibition of Rac1 could reduce ROS pro-duction and prevent oxidative
【机 构】
：
Department of Organ Transplantation,Second Affiliated Hospital of Naval Medical University,Shanghai,
论文部分内容阅读
Background and Aims: Reducing reactive oxygen species (ROS) production has proven an effective way for allevi-ating oxidative stress during ischemia-reperfusion injury (IRI). Moreover, inhibition of Rac1 could reduce ROS pro-duction and prevent oxidative stress injury. Previous stud-ies have suggested a positive interactivation feedback loop between Rac1 and hypoxia-inducible factor (HIF)-1α, the latter being up-regulated early during ischemia. The posi-tive inter-activation between Rac1 and HIF-1α would ag-gravate ROS production, thereby promoting IRI. This study was designed to verify the effects of Rac1 inhibition on he-patic IRI both at animal and cellular levels and to explore the interaction between Rac1 and HIF-1α during hepatic IRI. Methods: C57B/6 mice and AML-12 cells were used for the construction of hepatic IRI animal and cell models. Rac1 inhibition was achieved by NSC23766 (a specific Rac1 inhibitor). Lentiviral vectors were used for Rac1 knock-down. At designated time points, serum and liver tissues were collected from the mice and treated cells were col-lected for further analysis. Results: NSC23766 treatment significantly alleviated the hepatic IRI in mice, manifesting as lower vacuolation score and less apoptosis cells, lower ROS and serum/liver alanine aminotransferase/aspartate aminotransferase levels, and fewer activated inflammatory cells. IRI of AML-12 was also alleviated by 50 μM NSC23766 or Rac1-knockdown, manifesting as reduced cell apoptosis, less extensive interruption of mitochondrial membrane po-tential, down-regulation of apoptosis, and effects on DNA damage-related proteins. Interestingly, Rac1 knockdown also down-regulated the expression level of HIF-1α. Con-clusions: Our study supports a protective effect of Rac1 inhibition on hepatic IRI. Aside from the classic topics of reducing ROS production and oxidative stress, our study showed an interaction between Rac1 and HIF-1α signaling during hepatic IRI.
其他文献
心脏骤停（cardiac arrest, CA）是指心脏机械活动停止，循环征象消失的一种常见严重临床事件，其发病率高，生存率低，是全球面临的重要公共卫生问题之一。按发生CA地点区别，通常分为院外心脏骤停（out-of-hospital cardiac arrest, OHCA）和院内心脏骤停（in-hospital cardiac arrest, IHCA）。OHCA指发生在医院外所有场所的CA，被公认为是威胁人类健康的主要杀手之一，欧洲每年发生OHCA约28万例、美国约38万例、我国约为55万例n
严重的创伤性损伤持续给各地的医疗系统带来挑战，特别是在院前环境中对创伤患者的救治，研究表明创伤后早期死亡的主要原因仍是出血n [1,2]。急性创伤性凝血病（acute traumatic coagulopathy, ATC）是因急性严重创伤出血引起的纤维蛋白被纤溶酶降解所致机体凝血功能障碍n [3]。现有研究提出了早期识别和干预ATC的重要性n [4]。氨甲环酸（tranexamic acid, TXA）是具有稳定纤维蛋白作用的抗纤溶药n [5]，应用于择期手术能有效减少手
11月30日接到《中华急诊医学杂志》编辑老师的信息：“我刊2022年将开设急诊叙事医学栏目，特向您约稿。”看到这条信息我异常兴奋，终于在国内急诊最权威的学术期刊开展了叙事医学栏目。按理说从医这些年，不管是学术文章，还是人文文章都写作并发表了一些，不应对发表一篇文章欣喜若狂。但这次意义不同，以前写的文章都是各归其主，医学研究收录到专业学术期刊，叙事与人文收录到医学人文领域杂志。两个领域的期刊彼此没有交集，看专业，找不到人文；学人文，漏掉了专业。实际作为一名临床医务工作者，既要懂技术，又应知人文，因为医学是人
目的:观察以Pit-Crew心肺复苏（cardiopulmonary resuscitation, CPR）模式的团队复苏对胸外按压质量改善的效果。方法:采用对照研究的方法，将64名重症医学科和急诊科医护人员按照医护比例分成角色分工组与未角色分工组，每组各8队，每队4人。角色分工组每队指定一名队长组织协调整个CPR流程，未角色分工组不进行指定。每队利用高级模拟人在CPR质量跟踪反馈系统的监测下，按照《2020年美国心脏协会心肺复苏和心血管急救指南》推荐要求实施标准胸外心脏按压8 min。观察并记录每队实验
目的:探讨钙库操纵的钙离子通道（store-operated calcium entry, SOCE）抑制剂SKF96365对百草枯（paraquat, PQ）致肝肾损伤的作用。方法:体外培养A549细胞，分为对照组（DMSO组、SKF 2 μmol/L组，SKF 10 μmol/L组)，PQ组（PQ+DMSO组、PQ+SKF 2 μmol/L组，PQ+SKF 10 μmol/L组）。采用荧光素酶报告基因技术检测A549细胞活化T细胞核因子（nuclear factor of activated T ce
目的:探索左西孟旦在改善大鼠心肺复苏后急性肾损伤中的机制。方法:将25只健康成年雄性SD大鼠采用随机数字表法分为左西孟旦治疗组（治疗组，10只）、实验组（10只）和对照组（5只）。治疗组和实验组采用窒息法建立心脏骤停-心肺复苏模型，治疗组在复苏期间及复苏后予以左西孟旦干预，实验组在复苏期间及复苏后予以等剂量生理盐水处理，对照组不进行心脏骤停和心肺复苏操作，予以等剂量生理盐水处理。复苏6 h后将3组大鼠处死，检测大鼠血清中肌酐（serum creatinine，Scr）、尿素氮（blood urea nit
Background and Aims: Correct identification of small hepa-tocellular carcinomas (HCCs) and benign nodules in cirrhosis remains challenging, quantitative apparent diffusion coeffi-cients (ADCs) have shown potential value in characterization of benign and m
院外心脏骤停（out-of-hospital cardiac arrest, OHCA）是最严重的急危重症之一。虽然中国整体医疗水平近30年显著提高，但OHCA出院生存率未见显著提高（仍为1%），每年疾病经济负担高达317.8亿元n [1]。OHCA救治能力优化提升是中国医疗救治体系面临的核心难题之一。与慢性病救治不同，OHCA仅有“黄金10分钟”的抢救时间。中国的急救反应时间平均为16 minn [2]，仅靠救护车医护人员到达现场救治OHCA患者，显然不能满足OHCA突发性和时间敏感性的
Background and Aims: Metabolic dysfunction-associ-ated fatty liver disease (MAFLD) is a new concept, pro-posed in 2020; however, its applicability in Asia populations has yet to be evaluated. Therefore, we aimed to compare the difference in epidemiologica
Cirrhosis, an end stage of any chronic liver disease is a form of impaired regeneration leading to progressive dif-fuse hepatic fibrosis. The healthcare burden of cirrhosis is increasing, and it is currently the 13th leading cause of death globally. The p