{"title":"n -乙酰半胱氨酸对雄性大鼠脑缺血再灌注海马组织凋亡及NGF-Akt/Bad通路的影响。","authors":"Hamed Saniei, Roya Naderi","doi":"10.1007/s11011-025-01641-7","DOIUrl":null,"url":null,"abstract":"<p><p>Apoptosis is the primary pathological feature of neuronal injury caused by cerebral ischemia-reperfusion (I/R). The detailed molecular mediators are still being debated. This study aims to examine the effects of cerebral ischemia-reperfusion on apoptosis and NGF-Akt/Bad axis in rat hippocampus alone and in combination with NAC (N-Acetylcysteine). Rats were subjected to common carotid artery occlusion (CCAO) for 20 min followed by 24 h reperfusion. NAC (150 mg/kg) was given intraperitoneally (ip) one hour before ischemia and five minutes before reperfusion. TUNEL staining of hippocampus neurons revealed that the number of apoptotic neurons was elevated 24 h after reperfusion. At the molecular levels, I/R injury resulted in an increased protein expression of cleaved caspase3/procaspase3 ratio and cytochrome c level with a concomitant down-regulation of NGF, p-AKT/AKT, p-Bad/Bad and p-Trk/Trk ratio. NAC treatment significantly reduced the apoptotic damage and also reversed NGF, p-AKT/AKT, p-Bad/Bad, and p-Trk/Trk ratio in hippocampus neurons in I/R rats. In conclusion, our data showed that NGF-Akt/Bad axis may play a regulatory role in hippocampus cell death, providing a new target for a novel therapeutic strategy during transit ischemic stroke. NAC has been shown to reverse molecular alterations, suggesting its potential as an effective agent against hippocampal apoptosis following acute I/R injury.</p>","PeriodicalId":18685,"journal":{"name":"Metabolic brain disease","volume":"40 5","pages":"217"},"PeriodicalIF":3.5000,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The effect of N-acetylcysteine on apoptosis and NGF-Akt/Bad pathway in the hippocampus tissue of cerebral ischemia-reperfusion in male rats.\",\"authors\":\"Hamed Saniei, Roya Naderi\",\"doi\":\"10.1007/s11011-025-01641-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Apoptosis is the primary pathological feature of neuronal injury caused by cerebral ischemia-reperfusion (I/R). The detailed molecular mediators are still being debated. This study aims to examine the effects of cerebral ischemia-reperfusion on apoptosis and NGF-Akt/Bad axis in rat hippocampus alone and in combination with NAC (N-Acetylcysteine). Rats were subjected to common carotid artery occlusion (CCAO) for 20 min followed by 24 h reperfusion. NAC (150 mg/kg) was given intraperitoneally (ip) one hour before ischemia and five minutes before reperfusion. TUNEL staining of hippocampus neurons revealed that the number of apoptotic neurons was elevated 24 h after reperfusion. At the molecular levels, I/R injury resulted in an increased protein expression of cleaved caspase3/procaspase3 ratio and cytochrome c level with a concomitant down-regulation of NGF, p-AKT/AKT, p-Bad/Bad and p-Trk/Trk ratio. NAC treatment significantly reduced the apoptotic damage and also reversed NGF, p-AKT/AKT, p-Bad/Bad, and p-Trk/Trk ratio in hippocampus neurons in I/R rats. In conclusion, our data showed that NGF-Akt/Bad axis may play a regulatory role in hippocampus cell death, providing a new target for a novel therapeutic strategy during transit ischemic stroke. NAC has been shown to reverse molecular alterations, suggesting its potential as an effective agent against hippocampal apoptosis following acute I/R injury.</p>\",\"PeriodicalId\":18685,\"journal\":{\"name\":\"Metabolic brain disease\",\"volume\":\"40 5\",\"pages\":\"217\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Metabolic brain disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11011-025-01641-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolic brain disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11011-025-01641-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
The effect of N-acetylcysteine on apoptosis and NGF-Akt/Bad pathway in the hippocampus tissue of cerebral ischemia-reperfusion in male rats.
Apoptosis is the primary pathological feature of neuronal injury caused by cerebral ischemia-reperfusion (I/R). The detailed molecular mediators are still being debated. This study aims to examine the effects of cerebral ischemia-reperfusion on apoptosis and NGF-Akt/Bad axis in rat hippocampus alone and in combination with NAC (N-Acetylcysteine). Rats were subjected to common carotid artery occlusion (CCAO) for 20 min followed by 24 h reperfusion. NAC (150 mg/kg) was given intraperitoneally (ip) one hour before ischemia and five minutes before reperfusion. TUNEL staining of hippocampus neurons revealed that the number of apoptotic neurons was elevated 24 h after reperfusion. At the molecular levels, I/R injury resulted in an increased protein expression of cleaved caspase3/procaspase3 ratio and cytochrome c level with a concomitant down-regulation of NGF, p-AKT/AKT, p-Bad/Bad and p-Trk/Trk ratio. NAC treatment significantly reduced the apoptotic damage and also reversed NGF, p-AKT/AKT, p-Bad/Bad, and p-Trk/Trk ratio in hippocampus neurons in I/R rats. In conclusion, our data showed that NGF-Akt/Bad axis may play a regulatory role in hippocampus cell death, providing a new target for a novel therapeutic strategy during transit ischemic stroke. NAC has been shown to reverse molecular alterations, suggesting its potential as an effective agent against hippocampal apoptosis following acute I/R injury.
期刊介绍:
Metabolic Brain Disease serves as a forum for the publication of outstanding basic and clinical papers on all metabolic brain disease, including both human and animal studies. The journal publishes papers on the fundamental pathogenesis of these disorders and on related experimental and clinical techniques and methodologies. Metabolic Brain Disease is directed to physicians, neuroscientists, internists, psychiatrists, neurologists, pathologists, and others involved in the research and treatment of a broad range of metabolic brain disorders.