Acupuncture protects against cerebral ischemia-reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis

Sun, Xiaowei; Líu, Hao; Sun, Zhaoqing; Zhang, Beng; Wang, Xinyu; Liu, Tingting; Pan, Tingting; Gao, Ying; Jiang, Xicheng; Li, Hongtao

doi:10.21203/rs.3.rs-56735/v2

Cited by 4 publications

(4 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 Meanwhile, rapamycin is a known and efficacious mTOR inhibitor. 11 Recently, researchers confirmed 14,15 that acupuncture could induce or inhibit autophagy by improving endoplasmic reticulum stress (ERS) and regulating specific autophagy pathways, thus preserving nerve function and ameliorating neurological diseases. However, the specific mechanism remains unclear in acupuncture regulating autophagy to provide a neuroprotective effect after TBI.…”

Section: Introductionmentioning

confidence: 99%

Acupuncture promotes nerve repair through the benign regulation of mTOR‐mediated neuronal autophagy in traumatic brain injury rats

et al. 2022

View full text Add to dashboard Cite

Aims Recent investigations have already proved the neuroprotective efficacy of acupuncture in clinical practice in the treatment of neurological diseases, such as traumatic brain injury (TBI). Since growing evidence has suggested that neuronal autophagy was involved in multiple stages of TBI, this study aims to clarify the autophagy mediating mechanism underlying the neuroprotective effect of acupuncture in TBI rats. Methods Three experiments were carried out to detect changes in neuronal autophagy and identify the potential molecular mechanism underlying the neuroprotective effect of acupuncture for TBI treatment. Feeney's free‐falling epidural impingement method was used to establish the moderate TBI rat model; modified neurological severity scoring (mNSS) was used for neurological recovery evaluation. Nissl and HE staining were used to examine the histopathological changes. Immunofluorescence was used to detect the LC3‐positive cell rate. The transmission electron microscope (TEM) was used to investigate the morphology and quantity of autophagosomes. Western blotting was used to determine the protein expressions of LC3, p62, beclin1, mTOR, ULK1, p‐mTOR, and p‐ULK1. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used for gene expressions analysis of LC3 mRNA and p62 mRNA. Co‐immunoprecipitation (CO‐IP) method was used to identify the protein interaction of mTOR and ULK1. Results On Day 3 after TBI, acupuncture accelerated the removal of damaged cellular structures by promoting neuronal autophagy; on Day 7 and Day 14 after TBI, acupuncture inhibited neuronal autophagy, preventing excessive autophagy and thus alleviated nerve damage. In addition, the simultaneous treatment with 3‐MA or rapamycin at different stages after TBI attenuated the effect of acupuncture. Conclusion Acupuncture has a benign regulatory effect on neuronal autophagy in different stages of TBI, possibly through the mTOR/ULK1 pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

Acupuncture promotes nerve repair through the benign regulation of mTOR‐mediated neuronal autophagy in traumatic brain injury rats

et al. 2022

View full text Add to dashboard Cite

show abstract

“…An increasing number of studies have shown that autophagy plays an important role during cerebral I/R injury and is frequently mediated by oxidative stress, endoplasmic reticulum stress, and other reactions in cells after MCAO/R [ 24 , 25 ]. BHD plays a protective role against ischemic stroke with multiple targets, such as oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Buyang Huanwu Decoction on Cerebral Ischemia Reperfusion Injury by Alleviating Autophagy in the Ischemic Penumbra

Zhao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Objectives. To evaluate the protective effect of Buyang Huanwu Decoction (BHD) against cerebral ischemia reperfusion and investigate whether autophagy is involved in its mechanism of action. Methods. Adult male Sprague Dawley rats were randomly divided into three groups: the sham, cerebral ischemia reperfusion (I/R), and I/R + BHD groups. A rat model of cerebral I/R injury was established via middle cerebral artery occlusion (MCAO) for 2 h, followed by 1, 3, and 7 d of reperfusion. Neurological scores and regional cerebral blood flow were assessed to determine whether the model was successfully established. Brain infarct volume was determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. The apoptosis rate was detected using TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, and neuronal damage was evaluated by Nissl staining. The Beclin-1 and LC3 protein levels in the ischemic core, penumbra, and contralateral area were analysed by Western blotting. The occurrence of autophagy in the penumbra was observed by transmission electron microscopy (TEM). Results. BHD treatment alleviated the cerebral infarct volume, neuronal apoptosis rate, and neuronal damage 3 and 7 d after cerebral I/R injury. Furthermore, 3 d after reperfusion, we observed that the Beclin-1 levels were significantly decreased in the core in the I/R group, whereas transformation of LC3 I to LC3 II exhibited no obvious differences between the sham and I/R groups. In the penumbra, the Beclin-1 levels and transformation of LC3 I to LC3 II in the I/R group were significantly increased compared with that in the sham group. However, no significant difference in the contralateral area was noted between the two groups. BHD significantly inhibited the expression of Beclin-1 and the transformation of LC3 I to LC3 II in the penumbra after cerebral I/R injury but yielded no significant changes in the core and contralateral area. Conclusions. BHD exerts a neuroprotective effect by inhibiting autophagy in neurons in the penumbra after cerebral I/R injury.

show abstract

“…Neurological score (mNSS) was detected as described in a previous study by a researcher blind to the treatment groups before the rats were killed by rapid cervical dislocation 34 . Scores ranging from 0–18 (0 was considered as normal, whereas 18 represented the maximum nerve function defect) were given for four tests, including movement, sensation, balance beam, and reflex.…”

Section: Methodsmentioning

confidence: 99%

Icariin attenuates ischaemic stroke through suppressing inflammation mediated by endoplasmic reticulum stress signalling pathway in rats

Zheng

Liao²,

et al. 2022

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Ischaemic stroke possesses the characteristics of high incidence, high disability and high mortality. Icariin (ICA) is a flavonoid extracted from the traditional Chinese medicine Epimedium. The protective effect of ICA on ischaemic stroke is worthy of further study. In this study, male Sprague-Dawley rats were randomly divided into the following seven groups: sham, model, ICA low-dose (10 mg/kg), ICA medium-dose (20 mg/kg), ICA high-dose (40 mg/kg), positive control drug (12 mg/kg nimodipine) and endoplasmic reticulum stress induction (0.16 mg/kg tunicamycin) groups. The model of cerebral ischaemia-reperfusion injury in the rats, including 2 h ischaemia and 24 h reperfusion, was accomplished by applying the method of transient middle cerebral artery occlusion (MCAO). At 24 h reperfusion, neurological deficits, brain water content, pathological damage of brain tissues, the expression of inflammationrelated targets, and the signal pathway-related proteins were explored. Compared with the model group, ICA significantly improved neurological deficits, brain oedema and pathological damage after MCAO. In addition, ICA increased neuron survival, reduced microglial activation and expression of IL-1β, alleviating the inflammatory damage caused by ischaemic stroke. Moreover, ICA suppressed the expressions of glucose-regulated protein 78 (GRP78), inositol requiring enzyme-1 α (IRE1α), phospho-IRE1α (p-IRE1α), protein kinase RNA-like ER kinase (PERK), phospho-PERK (p-PERK), spliced XBP1 (XBP1s), unspliced XBP1 (XBP1u), thioredoxin-interacting protein (TXNIP), NLRP3, and caspase-1. These results suggested that ICA offers neuroprotection against ischaemic stroke by inhibiting ER stress-mediated inflammation.

show abstract

Acupuncture protects against cerebral ischemia-reperfusion injury via suppressing endoplasmic reticulum stress-mediated autophagy and apoptosis

Cited by 4 publications

References 3 publications

Acupuncture promotes nerve repair through the benign regulation of mTOR‐mediated neuronal autophagy in traumatic brain injury rats

Acupuncture promotes nerve repair through the benign regulation of mTOR‐mediated neuronal autophagy in traumatic brain injury rats

Protective Effect of Buyang Huanwu Decoction on Cerebral Ischemia Reperfusion Injury by Alleviating Autophagy in the Ischemic Penumbra

Icariin attenuates ischaemic stroke through suppressing inflammation mediated by endoplasmic reticulum stress signalling pathway in rats

Contact Info

Product

Resources

About