神经系统控制着我们全身的功能活动,出现问题可导致认知障碍、活动障碍、感觉障碍、疼痛等症状,仍然是对人类健康的最严重威胁之一。由于其难以察觉的症状,很难确定神经系统疾病的发病机制和治疗方法。Nrf2/HO-1轴因其在对抗氧化应激中...神经系统控制着我们全身的功能活动,出现问题可导致认知障碍、活动障碍、感觉障碍、疼痛等症状,仍然是对人类健康的最严重威胁之一。由于其难以察觉的症状,很难确定神经系统疾病的发病机制和治疗方法。Nrf2/HO-1轴因其在对抗氧化应激中的关键作用而被公认,作为抗氧化系统的调节剂,它上调HO-1的表达以减少氧化应激。Nrf2/HO1信号通路还参与调控细胞的凋亡、自噬、焦亡和铁死亡等病理生理过程,产生器官保护作用。鉴于Nrf2/HO-1在调节体内平衡中的重要性,本文综述了目前关于部分神经系统疾病与Nrf2/HO-1信号转导轴之间关系的研究。The nervous system controls the functional activities of our entire body, and problems can lead to symptoms such as cognitive impairment, activity impairment, sensory impairment, and pain, which remain one of the most serious threats to human health. Due to its imperceptible symptoms, it is difficult to determine the pathogenesis and treatment methods of neurological diseases. The Nrf2/HO-1 axis is recognized for its crucial role in combating oxidative stress and as a regulator of the antioxidant system, it upregulates the expression of HO-1 to reduce oxidative stress. The Nrf2/HO-1 signaling pathway is also involved in regulating pathological and physiological processes such as apoptosis, autophagy, pyroptosis, and ferroptosis in cells, producing organ protective effects. Given the importance of Nrf2/HO-1 in regulating homeostasis, this article reviews current research on the relationship between some neurological diseases and the Nrf2/HO-1 signaling pathway.展开更多
基金This work was supported by the National Natural Science Foundation of China (No. 30400094)the Scientific Research Foundation ofEducation Ministry of China for the Returned Overseas Chinese Scholars (No. 419100-G50619).
文摘本文旨在研究冠状动脉内皮和NO在选择性环加氧酶2(cyclooxygenase 2,COX-2)抑制剂尼美舒利(nimesulide)对抗心肌氧化损伤中的作用。离体大鼠心脏行Langendorff灌流,给予H2O2(140μmol/L)观察心脏收缩功能。用U-46619灌流心脏,使冠状动脉预收缩后,观察冠状动脉对内皮依赖性舒张因子5-HT和内皮非依赖性舒张因子硝普钠(sodium nitroprusside,SNP)的反应。结果显示:(1)与空白对照组(100%)相比,H2O2灌流20min后,左心室发展压[left ventricular developed pressure,LVDP,(54.8±4.0)%],和心室内压最大变化速率[±dp/dtmax,(50.8±3.1)%和(46.2±2.9)%]明显降低。H2O2灌流前尼美舒利(5μmol//L)预处理10min,能够显著抑制H2O2引起的LVDP和±dp/dtmax下降[(79.9±2.8)%,(80.3±2.6)%和(81.4±2.6)%,P<0.01]。(2)与空白对照组相比,H2O2灌流后,5-HT和SNP引起内皮依赖性和内皮非依赖性血管舒张功能均明显下降;而尼美舒利预处理10min能明显对抗内皮依赖性血管舒张功能的下降[(-22.2±4.2)%vsH2O2组(-6.0±2.5)%,P<0.01],但对其内皮非依赖性血管舒张功能的下降没有明显作用[(-2.0±1.8)%vsH2O2组(-7.0±3.5)%,P>0.05]。(3)一氧化氮合酶(nitric oxides ynthase,NOS)抑制剂L-NAME能够部分取消尼美舒利预处理对H2O2应激心脏心功能指标的改善作用[LVDP和±dp/dtmax分别为(60.2±2.1)%,(63.9±2.4)%和(63.1±2.9)%,P<0.01]。同时尼美舒利预处理10min能使H2O2应激心肌NO含量增加[(2.63±0.40)vs(1.36±0.23)nmol/gprotein,P<0.05],而L-NAME抑制此作用。(4)选择性COX-1抑制剂吡罗昔康(piroxicam)预处理不能抑制H2O2引起的LVDP和±dp/dtmax下降,但促进左心室舒张末压(left ventricular end diastolic pressure,LVEDP)升高;吡罗昔康对H2O2引起的内皮依赖性和内皮非依赖性血管舒张功能下降无显著作用。以上结果提示,选择性COX-2抑制剂尼美舒利能够对抗大鼠离体心肌氧化应激损伤,其机制可能是通过改善内皮依赖性血管舒张功能和增加心肌NO含量起作用。
文摘神经系统控制着我们全身的功能活动,出现问题可导致认知障碍、活动障碍、感觉障碍、疼痛等症状,仍然是对人类健康的最严重威胁之一。由于其难以察觉的症状,很难确定神经系统疾病的发病机制和治疗方法。Nrf2/HO-1轴因其在对抗氧化应激中的关键作用而被公认,作为抗氧化系统的调节剂,它上调HO-1的表达以减少氧化应激。Nrf2/HO1信号通路还参与调控细胞的凋亡、自噬、焦亡和铁死亡等病理生理过程,产生器官保护作用。鉴于Nrf2/HO-1在调节体内平衡中的重要性,本文综述了目前关于部分神经系统疾病与Nrf2/HO-1信号转导轴之间关系的研究。The nervous system controls the functional activities of our entire body, and problems can lead to symptoms such as cognitive impairment, activity impairment, sensory impairment, and pain, which remain one of the most serious threats to human health. Due to its imperceptible symptoms, it is difficult to determine the pathogenesis and treatment methods of neurological diseases. The Nrf2/HO-1 axis is recognized for its crucial role in combating oxidative stress and as a regulator of the antioxidant system, it upregulates the expression of HO-1 to reduce oxidative stress. The Nrf2/HO-1 signaling pathway is also involved in regulating pathological and physiological processes such as apoptosis, autophagy, pyroptosis, and ferroptosis in cells, producing organ protective effects. Given the importance of Nrf2/HO-1 in regulating homeostasis, this article reviews current research on the relationship between some neurological diseases and the Nrf2/HO-1 signaling pathway.
