针刺通过调节线粒体自噬-NLRP3炎性小体通路减轻急性缺血性卒中延迟rt-PA治疗后的出血转化。
Acupuncture alleviates hemorrhagic transformation after delayed rt-PA treatment for acute ischemic stroke by regulating the mitophagy-NLRP3 inflammasome pathway.
作者信息
Jiang Tao, Liu Qianqian, Liu Huanhuan, Huang Zheng, Yang Mengning, Huang Peiyan, Shen Yiting, Song Yangyang, Xu Wentao, Zhang Xinchang, Ni Guangxia
机构信息
College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, Nanjing, China.
Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.
出版信息
Front Neurol. 2025 Apr 7;16:1533092. doi: 10.3389/fneur.2025.1533092. eCollection 2025.
BACKGROUND
The clinical application of recombinant tissue plasminogen activator (rt-PA) is significantly constrained by hemorrhagic transformation (HT), a common and severe complication following thrombolysis for ischemic stroke. Notably, the mitochondrial injury-mediated NLRP3 inflammasome plays a crucial role in HT after delayed rt-PA thrombolysis in acute ischemic stroke. Although acupuncture has demonstrated antioxidant and anti-inflammatory effects in acute cerebral infarction, its impact on delayed rt-PA thrombolysis, especially concerning mitophagy and the NLRP3 inflammasome, remains unclear. This study investigates how acupuncture protects against HT resulting from mitochondrial damage and NLRP3 inflammasome activation after delayed rt-PA thrombolysis in acute cerebral stroke.
METHODS
We selected an embolic stroke model in rats and assessed brain injury after delayed rt-PA in acute ischemic stroke using neurological deficit score, volume of brain infarct, the permeability assay of the blood-brain barrier (BBB), and HT. Then, the levels of proteins and mRNA involved in mitophagy and the NLRP3 inflammasome pathway were measured by western blot and real-time PCR. The levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were assessed using enzyme-linked immunosorbent assay (ELISA). Morphological changes in the BBB and mitochondria of neurons were observed via transmission electron microscopy.
RESULTS
Acupuncture significantly improved neurological deficit scores, volume of cerebral infarction, BBB destruction, and HT in an embolic stroke model rat. Furthermore, acupuncture induced mitophagy and substantially downregulated the activity of the NLRP3 inflammasome. Additionally, the use of mitochondrial inhibitors significantly reversed the suppressive impact of acupuncture on the NLRP3 inflammasome.
CONCLUSION
Acupuncture can promote mitophagy and suppress NLRP3 inflammasome activation to decrease HT after delayed rt-PA therapy for acute ischemic stroke.
背景
重组组织型纤溶酶原激活剂（rt-PA）的临床应用受到出血性转化（HT）的显著限制，HT是缺血性中风溶栓后常见且严重的并发症。值得注意的是，线粒体损伤介导的NLRP3炎性小体在急性缺血性中风延迟rt-PA溶栓后的HT中起关键作用。尽管针灸在急性脑梗死中已显示出抗氧化和抗炎作用，但其对延迟rt-PA溶栓的影响，尤其是关于线粒体自噬和NLRP3炎性小体的影响，仍不清楚。本研究探讨针灸如何预防急性脑中风延迟rt-PA溶栓后由线粒体损伤和NLRP3炎性小体激活导致的HT。
方法
我们选用大鼠栓塞性中风模型，使用神经功能缺损评分、脑梗死体积、血脑屏障（BBB）通透性测定和HT评估急性缺血性中风延迟rt-PA后的脑损伤。然后，通过蛋白质印迹法和实时聚合酶链反应测量参与线粒体自噬和NLRP3炎性小体途径的蛋白质和mRNA水平。使用酶联免疫吸附测定（ELISA）评估白细胞介素-18（IL-18）和白细胞介素-1β（IL-1β）水平。通过透射电子显微镜观察BBB和神经元线粒体的形态变化。
结果
针灸显著改善了栓塞性中风模型大鼠的神经功能缺损评分、脑梗死体积、BBB破坏和HT。此外，针灸诱导了线粒体自噬并显著下调了NLRP3炎性小体的活性。此外，使用线粒体抑制剂显著逆转了针灸对NLRP3炎性小体的抑制作用。
结论
针灸可促进线粒体自噬并抑制NLRP3炎性小体激活，以减少急性缺血性中风延迟rt-PA治疗后的HT。
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