Luyao Qiao, Shouqin Yi, Tianpei Li, Xin Pan, Gege Wang, Xu Liu, Min Li, Jun Min, Huahui Le, Zhenyu Tang
{"title":"钙蛋白通过调节TXNIP/NLRP3炎性体改善糖尿病大鼠阿尔茨海默病样并发症的认知功能","authors":"Luyao Qiao, Shouqin Yi, Tianpei Li, Xin Pan, Gege Wang, Xu Liu, Min Li, Jun Min, Huahui Le, Zhenyu Tang","doi":"10.1111/jdi.14292","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>Diabetes mellitus (DM) is closely associated with Alzheimer's disease (AD), and is considered an accelerator of AD. Our previous study has confirmed that the Calpain inhibitor Calpeptin may alleviate AD-like complications of diabetes mellitus. This work further investigated its underlying mechanism.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>Diabetes mellitus rat model was constructed by a high-fat and high-sugar diet combined with streptozotocin, followed by the administration of Calpeptin. Moreover, rats were micro-injected with LV-TXNIP-OE/vector into the CA1 region of the hippocampus one day before streptozotocin injection. The Morris water maze test assessed the spatial learning and memory ability of rats. Immunohistochemistry and western blotting detected the expression of the pericyte marker PDGFRβ, tight junction proteins occludin and ZO-1, calpain-1, calpain-2, APP, Aβ, Aβ-related, and TXNIP/NLRP3 inflammasome-related proteins. Immunofluorescence staining examined the blood vessel density and neurons in the hippocampus. Evans blue extravasation and fluorescence detected the permeability of the blood–brain barrier (BBB) in rats. Additionally, the oxidative stress markers and inflammatory-related factors were assessed by enzyme-linked immunosorbent assay.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Calpeptin effectively reduced the expression of Calpain-2 and TXNIP/NLRP3 inflammasome-related proteins, improved the decreased pericyte marker (PDGFR-β) and cognitive impairment in hippocampus of DM rats. The neuronal loss, microvessel density, permeability of BBB, Aβ accumulation, inflammation, and oxidative stress injury in the hippocampus of DM rats were also partly rescued by calpeptin treatment. The influence conferred by calpeptin treatment was reversed by TXNIP overexpression.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These data demonstrated that calpeptin treatment alleviated AD-like symptoms in DM rats through regulating TXNIP/NLRP3 inflammasome. Thus, calpeptin may be a potential drug to treat AD-like complications of diabetes mellitus.</p>\n </section>\n </div>","PeriodicalId":51250,"journal":{"name":"Journal of Diabetes Investigation","volume":"15 10","pages":"1365-1376"},"PeriodicalIF":3.1000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11442751/pdf/","citationCount":"0","resultStr":"{\"title\":\"Calpeptin improves the cognitive function in Alzheimer's disease-like complications of diabetes mellitus rats by regulating TXNIP/NLRP3 inflammasome\",\"authors\":\"Luyao Qiao, Shouqin Yi, Tianpei Li, Xin Pan, Gege Wang, Xu Liu, Min Li, Jun Min, Huahui Le, Zhenyu Tang\",\"doi\":\"10.1111/jdi.14292\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>Diabetes mellitus (DM) is closely associated with Alzheimer's disease (AD), and is considered an accelerator of AD. Our previous study has confirmed that the Calpain inhibitor Calpeptin may alleviate AD-like complications of diabetes mellitus. This work further investigated its underlying mechanism.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Materials and Methods</h3>\\n \\n <p>Diabetes mellitus rat model was constructed by a high-fat and high-sugar diet combined with streptozotocin, followed by the administration of Calpeptin. Moreover, rats were micro-injected with LV-TXNIP-OE/vector into the CA1 region of the hippocampus one day before streptozotocin injection. The Morris water maze test assessed the spatial learning and memory ability of rats. Immunohistochemistry and western blotting detected the expression of the pericyte marker PDGFRβ, tight junction proteins occludin and ZO-1, calpain-1, calpain-2, APP, Aβ, Aβ-related, and TXNIP/NLRP3 inflammasome-related proteins. Immunofluorescence staining examined the blood vessel density and neurons in the hippocampus. Evans blue extravasation and fluorescence detected the permeability of the blood–brain barrier (BBB) in rats. Additionally, the oxidative stress markers and inflammatory-related factors were assessed by enzyme-linked immunosorbent assay.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Calpeptin effectively reduced the expression of Calpain-2 and TXNIP/NLRP3 inflammasome-related proteins, improved the decreased pericyte marker (PDGFR-β) and cognitive impairment in hippocampus of DM rats. The neuronal loss, microvessel density, permeability of BBB, Aβ accumulation, inflammation, and oxidative stress injury in the hippocampus of DM rats were also partly rescued by calpeptin treatment. The influence conferred by calpeptin treatment was reversed by TXNIP overexpression.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>These data demonstrated that calpeptin treatment alleviated AD-like symptoms in DM rats through regulating TXNIP/NLRP3 inflammasome. 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Calpeptin improves the cognitive function in Alzheimer's disease-like complications of diabetes mellitus rats by regulating TXNIP/NLRP3 inflammasome
Aims
Diabetes mellitus (DM) is closely associated with Alzheimer's disease (AD), and is considered an accelerator of AD. Our previous study has confirmed that the Calpain inhibitor Calpeptin may alleviate AD-like complications of diabetes mellitus. This work further investigated its underlying mechanism.
Materials and Methods
Diabetes mellitus rat model was constructed by a high-fat and high-sugar diet combined with streptozotocin, followed by the administration of Calpeptin. Moreover, rats were micro-injected with LV-TXNIP-OE/vector into the CA1 region of the hippocampus one day before streptozotocin injection. The Morris water maze test assessed the spatial learning and memory ability of rats. Immunohistochemistry and western blotting detected the expression of the pericyte marker PDGFRβ, tight junction proteins occludin and ZO-1, calpain-1, calpain-2, APP, Aβ, Aβ-related, and TXNIP/NLRP3 inflammasome-related proteins. Immunofluorescence staining examined the blood vessel density and neurons in the hippocampus. Evans blue extravasation and fluorescence detected the permeability of the blood–brain barrier (BBB) in rats. Additionally, the oxidative stress markers and inflammatory-related factors were assessed by enzyme-linked immunosorbent assay.
Results
Calpeptin effectively reduced the expression of Calpain-2 and TXNIP/NLRP3 inflammasome-related proteins, improved the decreased pericyte marker (PDGFR-β) and cognitive impairment in hippocampus of DM rats. The neuronal loss, microvessel density, permeability of BBB, Aβ accumulation, inflammation, and oxidative stress injury in the hippocampus of DM rats were also partly rescued by calpeptin treatment. The influence conferred by calpeptin treatment was reversed by TXNIP overexpression.
Conclusions
These data demonstrated that calpeptin treatment alleviated AD-like symptoms in DM rats through regulating TXNIP/NLRP3 inflammasome. Thus, calpeptin may be a potential drug to treat AD-like complications of diabetes mellitus.
期刊介绍：
Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).
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