{"title":"黄芩茎叶黄酮类化合物对复合 Aβ诱导大鼠髓鞘变性的影响及其机制","authors":"Xu Congcong, Ye Yuanyuan, Li Caixia, Shang Yazhen","doi":"10.2174/1871527322666230510103540","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease is a degenerative disease of the central nervous system, and its characteristic pathological changes are closely associated with Aβ deposition and neurofibrillary tangles. Many studies have found that malignant changes in the myelin sheath and oligodendrocyte (OL) are accompanied by the occurrence and development of AD. Therefore, any method that can resist myelin sheath and OL disorders may be a potential strategy for AD.</p><p><strong>Objective: </strong>To investigate the effects and mechanism of <i>Scutellaria baicalensis Georgi</i> stem and leaf flavonoids (SSFs) on the myelin sheath degeneration induced by Aβ<sub>25-35</sub> combined with AlC1<sub>3</sub> and RHTGF-β<sub>1</sub> (composite Aβ) in rats.</p><p><strong>Methods: </strong>A rat AD model was established by intracerebroventricular injection of composite Aβ. The Morris water maze was used to screen the memory impairment rat model. The successful model rats were divided into the model group and the 35, 70, and 140 mg/kg SSFS groups. The myelin sheath changes in the cerebral cortex were observed with an electron microscope. The expression of the oligodendrocyte- specific protein claudin 11 was detected with immunohistochemistry. The protein expression levels of myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG) and myelin basic protein (MBP), sphingomyelin synthase-1 (SMS1), and sphingomyelinase-2 (SMPD2) were assayed by Western blotting.</p><p><strong>Results: </strong>The intracerebroventricular injection of composite Aβ caused degeneration of the myelin sheath structure and was accompanied by the decreased claudin 11, MOG, MAG, MBP, and SMS1, and increased SMPD2 protein expression in the cerebral cortex. However, 35, 70, and 140 mg/kg SSFs can differentially ameliorate the above abnormal changes induced by composite Aβ.</p><p><strong>Conclusion: </strong>SSFs can alleviate myelin sheath degeneration and increase the protein expression of claudin 11, MOG, MAG, and MBP, and the effective mechanism may be related to the positive regulation of SMS1 and SMPD2 activities.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The Effects and Mechanism of <i>Scutellaria baicalensis Georgi</i> Stems and Leaves Flavonoids on Myelin Sheath Degeneration Induced by Composite Aβ in Rats.\",\"authors\":\"Xu Congcong, Ye Yuanyuan, Li Caixia, Shang Yazhen\",\"doi\":\"10.2174/1871527322666230510103540\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Alzheimer's disease is a degenerative disease of the central nervous system, and its characteristic pathological changes are closely associated with Aβ deposition and neurofibrillary tangles. Many studies have found that malignant changes in the myelin sheath and oligodendrocyte (OL) are accompanied by the occurrence and development of AD. Therefore, any method that can resist myelin sheath and OL disorders may be a potential strategy for AD.</p><p><strong>Objective: </strong>To investigate the effects and mechanism of <i>Scutellaria baicalensis Georgi</i> stem and leaf flavonoids (SSFs) on the myelin sheath degeneration induced by Aβ<sub>25-35</sub> combined with AlC1<sub>3</sub> and RHTGF-β<sub>1</sub> (composite Aβ) in rats.</p><p><strong>Methods: </strong>A rat AD model was established by intracerebroventricular injection of composite Aβ. The Morris water maze was used to screen the memory impairment rat model. The successful model rats were divided into the model group and the 35, 70, and 140 mg/kg SSFS groups. The myelin sheath changes in the cerebral cortex were observed with an electron microscope. The expression of the oligodendrocyte- specific protein claudin 11 was detected with immunohistochemistry. The protein expression levels of myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG) and myelin basic protein (MBP), sphingomyelin synthase-1 (SMS1), and sphingomyelinase-2 (SMPD2) were assayed by Western blotting.</p><p><strong>Results: </strong>The intracerebroventricular injection of composite Aβ caused degeneration of the myelin sheath structure and was accompanied by the decreased claudin 11, MOG, MAG, MBP, and SMS1, and increased SMPD2 protein expression in the cerebral cortex. However, 35, 70, and 140 mg/kg SSFs can differentially ameliorate the above abnormal changes induced by composite Aβ.</p><p><strong>Conclusion: </strong>SSFs can alleviate myelin sheath degeneration and increase the protein expression of claudin 11, MOG, MAG, and MBP, and the effective mechanism may be related to the positive regulation of SMS1 and SMPD2 activities.</p>\",\"PeriodicalId\":10456,\"journal\":{\"name\":\"CNS & neurological disorders drug targets\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS & neurological disorders drug targets\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/1871527322666230510103540\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS & neurological disorders drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1871527322666230510103540","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
背景：阿尔茨海默病是一种中枢神经系统退行性疾病，其特征性病理变化与 Aβ 沉积和神经纤维缠结密切相关。许多研究发现，髓鞘和少突胶质细胞（OL）的恶性变化伴随着 AD 的发生和发展。因此，任何能抵抗髓鞘和少突胶质细胞病变的方法都可能是治疗 AD 的潜在策略：研究黄芩茎叶黄酮（SSFs）对Aβ25-35联合AlC13和RHTGF-β1（复合Aβ）诱导的大鼠髓鞘变性的影响和机制：方法：通过脑室内注射复合 Aβ，建立大鼠 AD 模型。方法：通过脑室内注射复合 Aβ，建立大鼠注意力缺失模型。成功的模型大鼠被分为模型组和 35、70 和 140 mg/kg SSFS 组。用电子显微镜观察大脑皮层髓鞘的变化。用免疫组化方法检测少突胶质细胞特异性蛋白 claudin 11 的表达。用 Western 印迹法检测了髓鞘少突胶质细胞糖蛋白（MOG）、髓鞘相关糖蛋白（MAG）和髓鞘碱性蛋白（MBP）、鞘磷脂合成酶-1（SMS1）和鞘磷脂酶-2（SMPD2）的蛋白表达水平：结果：复合 Aβ 脑室内注射引起髓鞘结构变性，同时大脑皮层中 claudin 11、MOG、MAG、MBP 和 SMS1 蛋白表达减少，SMPD2 蛋白表达增加。然而，35、70 和 140 mg/kg SSFs 可不同程度地改善复合 Aβ 诱导的上述异常变化：结论：SSFs能缓解髓鞘变性，增加claudin 11、MOG、MAG和MBP的蛋白表达，其有效机制可能与SMS1和SMPD2活性的正向调节有关。
The Effects and Mechanism of Scutellaria baicalensis Georgi Stems and Leaves Flavonoids on Myelin Sheath Degeneration Induced by Composite Aβ in Rats.
Background: Alzheimer's disease is a degenerative disease of the central nervous system, and its characteristic pathological changes are closely associated with Aβ deposition and neurofibrillary tangles. Many studies have found that malignant changes in the myelin sheath and oligodendrocyte (OL) are accompanied by the occurrence and development of AD. Therefore, any method that can resist myelin sheath and OL disorders may be a potential strategy for AD.
Objective: To investigate the effects and mechanism of Scutellaria baicalensis Georgi stem and leaf flavonoids (SSFs) on the myelin sheath degeneration induced by Aβ25-35 combined with AlC13 and RHTGF-β1 (composite Aβ) in rats.
Methods: A rat AD model was established by intracerebroventricular injection of composite Aβ. The Morris water maze was used to screen the memory impairment rat model. The successful model rats were divided into the model group and the 35, 70, and 140 mg/kg SSFS groups. The myelin sheath changes in the cerebral cortex were observed with an electron microscope. The expression of the oligodendrocyte- specific protein claudin 11 was detected with immunohistochemistry. The protein expression levels of myelin oligodendrocyte glycoprotein (MOG), myelin-associated glycoprotein (MAG) and myelin basic protein (MBP), sphingomyelin synthase-1 (SMS1), and sphingomyelinase-2 (SMPD2) were assayed by Western blotting.
Results: The intracerebroventricular injection of composite Aβ caused degeneration of the myelin sheath structure and was accompanied by the decreased claudin 11, MOG, MAG, MBP, and SMS1, and increased SMPD2 protein expression in the cerebral cortex. However, 35, 70, and 140 mg/kg SSFs can differentially ameliorate the above abnormal changes induced by composite Aβ.
Conclusion: SSFs can alleviate myelin sheath degeneration and increase the protein expression of claudin 11, MOG, MAG, and MBP, and the effective mechanism may be related to the positive regulation of SMS1 and SMPD2 activities.
期刊介绍：
Aims & Scope
CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes.
CNS & Neurological Disorders - Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies.
As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
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