Hypoxic preconditioning can protect against cerebral ischemia/reperfusion injury. However, the underlying mechanisms that mediate this effect are not completely clear. In this study, mice were pretreated with continuo...Hypoxic preconditioning can protect against cerebral ischemia/reperfusion injury. However, the underlying mechanisms that mediate this effect are not completely clear. In this study, mice were pretreated with continuous, intermittent hypoxic preconditioning;1 hour later, cerebral ischemia/reperfusion models were generated by middle cerebral artery occlusion and reperfusion. Compared with control mice, mice with cerebral ischemia/reperfusion injury showed increased Bederson neurological function scores, significantly increased cerebral infarction volume, obvious pathological damage to the hippocampus, significantly increased apoptosis;upregulated interleukin-1β, interleukin-6, and interleukin-8 levels in brain tissue;and increased expression levels of NOD-like receptor family pyrin domain containing 3(NLRP3), NLRP inflammasome-related protein caspase-1, and gasdermin D. However, hypoxic preconditioning significantly inhibited the above phenomena. Taken together, these data suggest that hypoxic preconditioning mitigates cerebral ischemia/reperfusion injury in mice by reducing NLRP3 inflammasome expression. This study was approved by the Medical Ethics Committee of the Fourth Hospital of Baotou, China(approval No. DWLL2019001) in November 2019.展开更多
目的：通过建立成年大鼠心肌细胞缺氧复氧模型观察缺氧后处理的心肌保护机制。方法雄性SD大鼠，体质量250～350 g ，随机分为3组：正常组（NOR组）、缺氧组（H／R组）、缺氧后组（HP组）。采用激光共聚焦显微镜检测心肌细胞线粒体膜电位...目的：通过建立成年大鼠心肌细胞缺氧复氧模型观察缺氧后处理的心肌保护机制。方法雄性SD大鼠，体质量250～350 g ，随机分为3组：正常组（NOR组）、缺氧组（H／R组）、缺氧后组（HP组）。采用激光共聚焦显微镜检测心肌细胞线粒体膜电位（mitochondrial membrane potential ， MMP）、细胞内钙离子荧光强度以及 Western blot方法测定磷酸化 p38丝裂原活化蛋白激酶（p‐p38MAPK）表达量。结果（1）与正常组比较，H／R组和 HP组 MMP显著降低（P＜0．05）；HP组MMP明显高于 H／R组（P＞0．05）；（2）与正常组和 HP组比较，H／R组细胞内钙离子荧光强度显著升高（P＜0．01）；HP组和正常组间差异无统计学意义（P＞0．05）；（3）与正常组和 HP组比较，H／R组p‐p38MAPK表达量显著升高（P＜0．05）；HP组和正常组间表达量差异无统计学意义（P＞0．05）。结论缺氧后处理可对缺氧复氧成年大鼠心肌细胞产生保护作用，其机制可能与下调心肌细胞p‐p38M A PK 表达量、抑制线粒体膜电位下降以及防止钙超载进而抑制凋亡有关。展开更多
基金supported by National Natural Science Foundation of China,No.81771270(to QP)Inner Mongolia Science Foundation of China,No.2020MS08063(to YQP)+3 种基金Health and Family Planning Scientific Research Plan Project of Inner Mongolia Autonomous Region of China,No.201702138(to YQP)Baotou Science and Technology Plan Project of China,No.2018C2007-4-10(to YQP)Baotou Medical and Health Science and Technology Project of China,No.wsjj2019036(to JY)Baotou Medical College Foundation of China,No.BSJJ201904(to JY)。
文摘Hypoxic preconditioning can protect against cerebral ischemia/reperfusion injury. However, the underlying mechanisms that mediate this effect are not completely clear. In this study, mice were pretreated with continuous, intermittent hypoxic preconditioning;1 hour later, cerebral ischemia/reperfusion models were generated by middle cerebral artery occlusion and reperfusion. Compared with control mice, mice with cerebral ischemia/reperfusion injury showed increased Bederson neurological function scores, significantly increased cerebral infarction volume, obvious pathological damage to the hippocampus, significantly increased apoptosis;upregulated interleukin-1β, interleukin-6, and interleukin-8 levels in brain tissue;and increased expression levels of NOD-like receptor family pyrin domain containing 3(NLRP3), NLRP inflammasome-related protein caspase-1, and gasdermin D. However, hypoxic preconditioning significantly inhibited the above phenomena. Taken together, these data suggest that hypoxic preconditioning mitigates cerebral ischemia/reperfusion injury in mice by reducing NLRP3 inflammasome expression. This study was approved by the Medical Ethics Committee of the Fourth Hospital of Baotou, China(approval No. DWLL2019001) in November 2019.
