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针刺抑制 TXNIP 相关的氧化应激和炎症反应,减轻血管性痴呆大鼠的认知障碍。

Acupuncture inhibits TXNIP-associated oxidative stress and inflammation to attenuate cognitive impairment in vascular dementia rats.

机构信息

Acupuncture and Moxibustion Department, Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University, Beijing, China.

Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, China.

出版信息

CNS Neurosci Ther. 2018 Jan;24(1):39-46. doi: 10.1111/cns.12773. Epub 2017 Nov 6.

Abstract

AIMS

Oxidative stress and inflammation have been implicated in the pathogenesis of vascular dementia (VD). Thioredoxin-interacting protein (TXNIP) plays a vital role in oxidative stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation. There is evidence that acupuncture has an antioxidative and neuroprotective effect in VD. In this study, we investigated whether acupuncture can attenuate cognitive impairment via inhibiting TXNIP-associated oxidative stress and inflammation in VD rats.

METHODS

Both common carotid arteries were occluded (2-vessel occlusion [2VO]) in rats to model VD. The neuroprotective effect of acupuncture was assessed by the Morris water maze and Nissl staining. Oxidative stress was assessed by detecting levels of reactive oxygen species, DNA oxidation, and antioxidase. Western blot, real-time PCR, and immunofluorescence were used to detect the expression of TXNIP, NLRP3, caspase-1, and IL-1β. A TXNIP siRNA intraventricular injection was applied to investigate whether acupuncture mimicked the effect of TXNIP inhibitor.

RESULTS

Our findings demonstrated that VD rats treated with acupuncture had reduced hippocampal neuronal loss and oxidative stress. The upregulation of TXNIP, NLRP3, caspase-1, and IL-1β induced by 2VO was also reversed by acupuncture. Furthermore, TXNIP siRNA had a similar effect as acupuncture on cognition, hippocampal neurons, and ROS production in VD rats.

CONCLUSION

In conclusion, our study suggests that the neuroprotective effects of acupuncture in VD are mediated through reducing expression of TXNIP-associated oxidative stress and inflammation.

摘要

目的

氧化应激和炎症与血管性痴呆(VD)的发病机制有关。硫氧还蛋白相互作用蛋白(TXNIP)在氧化应激和 NOD 样受体蛋白 3(NLRP3)炎性小体激活中起着至关重要的作用。有证据表明,针刺在 VD 中具有抗氧化和神经保护作用。在这项研究中,我们研究了针刺是否可以通过抑制 VD 大鼠中与 TXNIP 相关的氧化应激和炎症来减轻认知障碍。

方法

通过双侧颈总动脉闭塞(2 血管闭塞[2VO])在大鼠中建立 VD 模型。通过 Morris 水迷宫和尼氏染色评估针刺的神经保护作用。通过检测活性氧、DNA 氧化和抗氧化酶的水平来评估氧化应激。Western blot、实时 PCR 和免疫荧光用于检测 TXNIP、NLRP3、caspase-1 和 IL-1β的表达。脑室注射 TXNIP siRNA 用于研究针刺是否模拟了 TXNIP 抑制剂的作用。

结果

我们的研究结果表明,针刺治疗的 VD 大鼠海马神经元丢失和氧化应激减少。2VO 诱导的 TXNIP、NLRP3、caspase-1 和 IL-1β 的上调也被针刺所逆转。此外,TXNIP siRNA 对 VD 大鼠认知、海马神经元和 ROS 产生的影响与针刺相似。

结论

总之,我们的研究表明,针刺在 VD 中的神经保护作用是通过减少与 TXNIP 相关的氧化应激和炎症表达来介导的。

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