Protective effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve of rats with diabetic peripheral neuropathy
Dyslipidemia has been considered a risk factor for diabetic peripheral neuropathy. Proprotein convertase subtilisin-like/Kexin 9 inhibitor (PCSK9) inhibitors are a new type of lipid-lowering drug currently in clinical use. The role of PCSK9 in diabetic peripheral neuropathy is still unclear. In this...
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| Published in | Endocrine Journal Vol. 71; no. 3; pp. 233 - 244 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Japan
The Japan Endocrine Society
01.01.2024
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| Abstract | Dyslipidemia has been considered a risk factor for diabetic peripheral neuropathy. Proprotein convertase subtilisin-like/Kexin 9 inhibitor (PCSK9) inhibitors are a new type of lipid-lowering drug currently in clinical use. The role of PCSK9 in diabetic peripheral neuropathy is still unclear. In this study, the effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve in rats with diabetic peripheral neuropathy and its underlying mechanisms were investigated. The diabetic peripheral neuropathy rat model was established by using a high-fat diet combined with streptozotocin injection, and experimental subjects were divided into normal, diabetic peripheral neuropathy, and alirocumab groups. The results showed that Alirocumab improved nerve conduction, morphological changes, and small fiber deficits in rats with DPN, possibly related to its amelioration of oxidative stress and the inflammatory response. |
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| AbstractList | Dyslipidemia has been considered a risk factor for diabetic peripheral neuropathy. Proprotein convertase subtilisin-like/Kexin 9 inhibitor (PCSK9) inhibitors are a new type of lipid-lowering drug currently in clinical use. The role of PCSK9 in diabetic peripheral neuropathy is still unclear. In this study, the effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve in rats with diabetic peripheral neuropathy and its underlying mechanisms were investigated. The diabetic peripheral neuropathy rat model was established by using a high-fat diet combined with streptozotocin injection, and experimental subjects were divided into normal, diabetic peripheral neuropathy, and alirocumab groups. The results showed that Alirocumab improved nerve conduction, morphological changes, and small fiber deficits in rats with DPN, possibly related to its amelioration of oxidative stress and the inflammatory response. Dyslipidemia has been considered a risk factor for diabetic peripheral neuropathy. Proprotein convertase subtilisin-like/Kexin 9 inhibitor (PCSK9) inhibitors are a new type of lipid-lowering drug currently in clinical use. The role of PCSK9 in diabetic peripheral neuropathy is still unclear. In this study, the effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve in rats with diabetic peripheral neuropathy and its underlying mechanisms were investigated. The diabetic peripheral neuropathy rat model was established by using a high-fat diet combined with streptozotocin injection, and experimental subjects were divided into normal, diabetic peripheral neuropathy, and alirocumab groups. The results showed that Alirocumab improved nerve conduction, morphological changes, and small fiber deficits in rats with DPN, possibly related to its amelioration of oxidative stress and the inflammatory response.Dyslipidemia has been considered a risk factor for diabetic peripheral neuropathy. Proprotein convertase subtilisin-like/Kexin 9 inhibitor (PCSK9) inhibitors are a new type of lipid-lowering drug currently in clinical use. The role of PCSK9 in diabetic peripheral neuropathy is still unclear. In this study, the effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve in rats with diabetic peripheral neuropathy and its underlying mechanisms were investigated. The diabetic peripheral neuropathy rat model was established by using a high-fat diet combined with streptozotocin injection, and experimental subjects were divided into normal, diabetic peripheral neuropathy, and alirocumab groups. The results showed that Alirocumab improved nerve conduction, morphological changes, and small fiber deficits in rats with DPN, possibly related to its amelioration of oxidative stress and the inflammatory response. |
| ArticleNumber | EJ23-0359 |
| Author | Lu, Xiuyan Cui, Na Feng, Yonghao Chen, Yinghui Huang, Yongmei Shi, Xiaohong Wang, Ming |
| Author_xml | – sequence: 1 fullname: Lu, Xiuyan organization: Department of Endocrinology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China – sequence: 1 fullname: Chen, Yinghui organization: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China – sequence: 1 fullname: Cui, Na organization: Department of Endocrinology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China – sequence: 1 fullname: Feng, Yonghao organization: Department of Endocrinology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China – sequence: 1 fullname: Shi, Xiaohong organization: Department of Endocrinology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China – sequence: 1 fullname: Wang, Ming organization: Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China – sequence: 1 fullname: Huang, Yongmei organization: Department of Electromyography, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38233122$$D View this record in MEDLINE/PubMed |
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| Keywords | Oxidative stress Inflammatory response Alirocumab Diabetic peripheral neuropathy Sciatic nerve |
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| References_xml | – reference: 15 Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, et al. (2019) 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the management of blood cholesterol: a report of the american college of cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 139: e1082–e1143. – reference: 17 Ding Z, Wang X, Liu S, Shahanawaz J, Theus S, et al. (2018) PCSK9 expression in the ischaemic heart and its relationship to infarct size, cardiac function, and development of autophagy. Cardiovasc Res 114: 1738–1751. – reference: 39 Vaughan TB, Bell DSH (2005) Statin Neuropathy Masquerading as Diabetic Autoimmune Polyneuropathy. Diabetes Care 28: 2082. – reference: 7 Eid S, Sas KM, Abcouwer SF, Feldman EL, Gardner TW, et al. (2019) New insights into the mechanisms of diabetic complications: role of lipids and lipid metabolism. Diabetologia 62: 1539–1549. – reference: 11 Wu YB, Shi LL, Wu YJ, Xu WH, Wang L, et al. (2012) Protective effect of gliclazide on diabetic peripheral neuropathy through Drp-1 mediated-oxidative stress and apoptosis. Neurosci Lett 523: 45–49. – reference: 12 Lin Q, Li K, Chen Y, Xie J, Wu C, et al. (2023) Oxidative stress in diabetic peripheral neuropathy: pathway and mechanism-based treatment. Mol Neurobiol 60: 4574–4594. – reference: 16 Momtazi-Borojeni AA, Sabouri-Rad S, Gotto AM, Pirro M, Banach M, et al. (2019) PCSK9 and inflammation: a review of experimental and clinical evidence. Eur Heart J Cardiovasc Pharmacother 5: 237–245. – reference: 23 Baum P, Kosacka J, Estrela-Lopis I, Woidt K, Serke H, et al. (2016) The role of nerve inflammation and exogenous iron load in experimental peripheral diabetic neuropathy (PDN). Metabolism 65: 391–405. – reference: 41 Pek SLT, Sum CF, Yeoh LY, Lee SBM, Tang WE, et al. 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| SubjectTerms | Alirocumab Diabetes mellitus Diabetic neuropathy Diabetic peripheral neuropathy Dyslipidemia High fat diet Inflammation Inflammatory response Kexin Nerve conduction Oxidative stress Peripheral neuropathy Proprotein convertases Risk factors Sciatic nerve Streptozocin Subtilisin |
| Title | Protective effect of alirocumab, a PCSK9 inhibitor, on the sciatic nerve of rats with diabetic peripheral neuropathy |
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