Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury

We investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial function in cerebral ischemia-reperfusion injury. Rats were randomly divided into 5 groups: sham, ischemia and reperfusion (IR), IR plus XXMD (60 g/kg/day) (XXMD60), IR plus cyclosporin A (10 mg/kg/day...

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Main Authors: Rui Lan, Yong Zhang, Tao Wu, Yun-Zhi Ma, Bao-Qi Wang, Hai-Zhong Zheng, Ya-Na Li, Yan Wang, Chun-Qing Gu, Ji-Tao Wu
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Behavioural Neurology
Online Access:http://dx.doi.org/10.1155/2018/4147502
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author Rui Lan
Yong Zhang
Tao Wu
Yun-Zhi Ma
Bao-Qi Wang
Hai-Zhong Zheng
Ya-Na Li
Yan Wang
Chun-Qing Gu
Ji-Tao Wu
author_facet Rui Lan
Yong Zhang
Tao Wu
Yun-Zhi Ma
Bao-Qi Wang
Hai-Zhong Zheng
Ya-Na Li
Yan Wang
Chun-Qing Gu
Ji-Tao Wu
author_sort Rui Lan
collection DOAJ
description We investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial function in cerebral ischemia-reperfusion injury. Rats were randomly divided into 5 groups: sham, ischemia and reperfusion (IR), IR plus XXMD (60 g/kg/day) (XXMD60), IR plus cyclosporin A (10 mg/kg/day) (CsA), and IR plus vehicle (Vehicle). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion (MCAO). Cerebral infarct areas were measured by triphenyl tetrazolium chloride staining. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining (HE) and Nissl staining. Ultrastructural features of mitochondria and mitophagy in the penumbra of the ischemic cortex were observed by transmission electron microscopy. Mitophagy was detected by immunofluorescence labeled with LC3B and VDAC1. Autophagy lysosome formation was observed by immunofluorescence labeled with LC3B and Lamp1. The expression of LC3B, Beclin1, and Lamp1 was analyzed by Western blot. The rats subjected to MCAO showed worsened neurological score and cell ischemic damage. These were all significantly reversed by XXMD or CsA. Moreover, XXMD/CsA notably downregulated mitophagy and reduced the increase in LC3, Beclin1, and Lamp1 expression induced by cerebral ischemia and reperfusion. The findings demonstrated that XXMD exerted neuroprotective effect via downregulating LC3, Beclin1, Lamp1, and mitochondrial p62 expression level, thus leading to the inhibition of mitophagy.
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issn 0953-4180
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publishDate 2018-01-01
publisher Wiley
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series Behavioural Neurology
spelling doaj-art-84fa9ba473284a21b129ad81988780902025-02-03T01:28:13ZengWileyBehavioural Neurology0953-41801875-85842018-01-01201810.1155/2018/41475024147502Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion InjuryRui Lan0Yong Zhang1Tao Wu2Yun-Zhi Ma3Bao-Qi Wang4Hai-Zhong Zheng5Ya-Na Li6Yan Wang7Chun-Qing Gu8Ji-Tao Wu9Encephalopathy Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan 450000, ChinaCerebral Palsy Rehabilitation Department, The Third Affiliated Hospital of Zhengzhou University, Henan 450000, ChinaEncephalopathy Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan 450000, ChinaEncephalopathy Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan 450000, ChinaHenan University of Chinese Medicine, Henan 450000, ChinaHenan University of Chinese Medicine, Henan 450000, ChinaEncephalopathy Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan 450000, ChinaEncephalopathy Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan 450000, ChinaEncephalopathy Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan 450000, ChinaEncephalopathy Hospital, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan 450000, ChinaWe investigated whether Xiao-Xu-Ming decoction reduced mitophagy activation and kept mitochondrial function in cerebral ischemia-reperfusion injury. Rats were randomly divided into 5 groups: sham, ischemia and reperfusion (IR), IR plus XXMD (60 g/kg/day) (XXMD60), IR plus cyclosporin A (10 mg/kg/day) (CsA), and IR plus vehicle (Vehicle). Focal cerebral ischemia and reperfusion models were induced by middle cerebral artery occlusion (MCAO). Cerebral infarct areas were measured by triphenyl tetrazolium chloride staining. Cerebral ischemic injury was evaluated by hematoxylin and eosin staining (HE) and Nissl staining. Ultrastructural features of mitochondria and mitophagy in the penumbra of the ischemic cortex were observed by transmission electron microscopy. Mitophagy was detected by immunofluorescence labeled with LC3B and VDAC1. Autophagy lysosome formation was observed by immunofluorescence labeled with LC3B and Lamp1. The expression of LC3B, Beclin1, and Lamp1 was analyzed by Western blot. The rats subjected to MCAO showed worsened neurological score and cell ischemic damage. These were all significantly reversed by XXMD or CsA. Moreover, XXMD/CsA notably downregulated mitophagy and reduced the increase in LC3, Beclin1, and Lamp1 expression induced by cerebral ischemia and reperfusion. The findings demonstrated that XXMD exerted neuroprotective effect via downregulating LC3, Beclin1, Lamp1, and mitochondrial p62 expression level, thus leading to the inhibition of mitophagy.http://dx.doi.org/10.1155/2018/4147502
spellingShingle Rui Lan
Yong Zhang
Tao Wu
Yun-Zhi Ma
Bao-Qi Wang
Hai-Zhong Zheng
Ya-Na Li
Yan Wang
Chun-Qing Gu
Ji-Tao Wu
Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury
Behavioural Neurology
title Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury
title_full Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury
title_fullStr Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury
title_full_unstemmed Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury
title_short Xiao-Xu-Ming Decoction Reduced Mitophagy Activation and Improved Mitochondrial Function in Cerebral Ischemia and Reperfusion Injury
title_sort xiao xu ming decoction reduced mitophagy activation and improved mitochondrial function in cerebral ischemia and reperfusion injury
url http://dx.doi.org/10.1155/2018/4147502
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