Stable Rat Model of Mechanical Allodynia in Diabetic Peripheral Neuropathy: The Role of Nerve Compression

Liao, Chenlong; Ye, Min; Liu, Pengfei; Zhong, Wenxiang; Zhang, Wenchuan

doi:10.1055/s-0037-1621723

Cited by 8 publications

(4 citation statements)

References 37 publications

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“…The STZ-induced rat model has been reported as a stable DPN model with thermal hyperalgesia and mechanical allodynia 15. We measured the MWT in the present study to evaluate the effects of JMT on mechanical allodynia in diabetic rats.…”

Section: Resultsmentioning

confidence: 99%

<p>Jinmaitong Ameliorates Diabetic Peripheral Neuropathy Through Suppressing TXNIP/NLRP3 Inflammasome Activation In The Streptozotocin-Induced Diabetic Rat Model</p>

Sun¹,

Wang²,

Yan³

et al. 2019

DMSO

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Background: Jinmaitong (JMT) has been used to prevent and treat diabetic peripheral neuropathy (DPN) for decades. The present study aimed to elucidate the effects of JMT on thioredoxin-interacting protein (TXNIP) and Nod-like receptor protein 3 (NLRP3) inflammasome activation in the streptozotocin (STZ)-induced rat model. Methods: The diabetic rat model was induced by a single intraperitoneal injection of 55 mg/ kg STZ. The rats were divided into 3 groups (n = 8-10 per group): diabetic control, JMT (0.876 g/kg/d), and alpha-lipoic acid (ALA; 100 mg/kg/d). Body weight and blood glucose levels were monitored every 4 weeks for 12 weeks. Mechanical allodynia and myelin sheath injury of sciatic nerves (SNs) were assessed using the mechanical withdrawal threshold (MWT) test and Luxol fast blue staining. Serum T-superoxide dismutase (T-SOD), malondialdehyde (MDA), and catalase (CAT) levels were measured using commercially available kits. TXNIP/NLRP3 inflammasome proteins, including TXNIP, NLRP3, pro-caspase-1, and cleaved -caspase-1, and the downstream protein interleukin (IL)-1β, were measured using immunohistochemistry and Western blot. Gasdermin D (GSDMDC1) protein expression was analyzed using Western blot, and serum IL-1β and IL-18 levels were detected using ELISA. Results: JMT did not significantly affect body weight or level of fasting blood glucose but improved mechanical allodynia and myelin sheath injury of SNs at 12 weeks following treatment. Moreover, JMT increased serum levels of the anti-oxidative enzymes CAT and T-SOD, and decreased MDA levels. Both JMT and ALA decreased expression of TXNIP, NLRP3, and cleaved-caspase-1 protein. JMT and ALA also decreased IL-1β, IL-18, and GSDMDC1 protein expression. Conclusion:The current study demonstrated that TXNIP/NLRP3 inflammasome activation is involved in the molecular mechanisms underlying JMT's protective effects in the STZ-induced diabetic rat model, which provides novel evidence to support the future clinical use of JMT.

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Section: Resultsmentioning

confidence: 99%

<p>Jinmaitong Ameliorates Diabetic Peripheral Neuropathy Through Suppressing TXNIP/NLRP3 Inflammasome Activation In The Streptozotocin-Induced Diabetic Rat Model</p>

Sun¹,

Wang²,

Yan³

et al. 2019

DMSO

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“…STZ-induced diabetic rats have been widely used for the histopathological, pharmaceutical, or neurological research of experimental DPN [38][39][40][41]. Yet few studies have performed microarray experiment on the peripheral nerve tissue of DPN rats with STZ-induced diabetes.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling of the Sciatic Nerve in Streptozotocin-Induced Diabetic Rats with Peripheral Neuropathy

Chen

Zhang

et al. 2020

Journal of Diabetes Research

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Aims. To investigate the candidate biomarkers and molecular mechanisms involved in the early phase of experimental diabetic peripheral neuropathy (DPN). Methods. Diabetes in Sprague-Dawley rats was induced with streptozotocin (STZ) treatment, followed with neurological tests and histological examinations to assess the neuropathic symptoms of DPN. Microarray was performed on the sciatic nerve tissues from control rats and DPN rats at then6th week after diabetes induction, and differentially expressed genes (DEGs) between them were identified and applied for further bioinformatic analyses. Results. Experimental DPN rats were successfully constructed, presenting significantly decreased withdrawal threshold and motor nerve conduction velocity, and typical histological changes in the sciatic nerve. 597 DEGs (186 up- and 411 downregulated) were identified in DPN rats. DEGs from the 3 most highly connected clusters in the protein-protein interaction network were enriched for biological processes or pathways such as “cell division,” “cell cycle,” “protein phosphorylation,” “chemokine signaling pathway,” “neuropeptide signaling pathway,” “response to drug,” “cellular response to insulin stimulus,” “PPAR signaling pathway,” and “glycerophospholipid metabolism.” Thirteen genes were identified as the hub DEGs in the PPI network. Eleven transcriptional factors (TFs) targeting 9 of the 13 hub DEGs were predicted. Conclusions. The present study identified a pool of candidate biomarkers such as Cdk1, C3, Mapk12, Agt, Adipoq, Cxcl2, and Mmp9 and molecular mechanisms which may be involved in the early phase of experimental DPN. The findings provide clues for exploring new strategies for the early diagnosis and treatment of DPN.

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“…As previously reported (Liao et al, 2018), type 1 diabetes was induced by a single intraperitoneal injection of STZ (Solarbio, China) in rats. In brief, STZ was dissolved in citrate buffer (pH = 4.6) at a concentration of 1%.…”

Section: Induction Of Type 1 Diabetesmentioning

confidence: 97%

Multi-omics analysis revealed the role of CYP1A2 in the induction of mechanical allodynia in type 1 diabetes

Chen

Liao²,

Yang³

et al. 2023

Front. Genet.

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Background: Mechanical allodynia (MA) is one of the leading clinical symptoms of painful diabetic peripheral neuropathy (PDPN), which is a primary reason for non-traumatic amputations, foot ulceration, and gait abnormalities in patients with diabetes. However, the pathogenic mechanisms of MA have not yet been fully elucidated, and there is no effective treatment. This study aims to study the potential pathogenetic mechanisms of MA and to provide targets for the therapy of MA.Methods: A single intraperitoneal injection of streptozotocin induced type 1 diabetes in rat models. Subsequently, rats were divided into the control group, the diabetic group without MA, and the diabetic group with MA based on weekly behavioral assays. The differentially expressed lipids in the sciatic nerve of each group were detected using untargeted lipidomics, and the differentially expressed genes in the sciatic nerve of each group were detected by transcriptomics. The pathogenesis of MA was predicted using integrated analysis and validated by immunofluorescence staining and transmission electron microscopy.Results: Untargeted lipidomics revealed the accumulation of a more severe lipid in MA rats. Transcriptomics results suggested that differentially expressed genes in MA rats were primarily related to lipid droplets and myelin sheath. Integrated analysis results indicated that the downregulation of Cytochrome P450 1A2 (CYP1A2) expression was closely linked to lipid metabolism disorders. Immunofluorescence staining demonstrated that down-regulation of CYP1A2 expression occurred in MA rats. Transmission electron microscopy results showed that more severe lipid droplet accumulation and myelin sheath degeneration occurred in MA rats.Conclusion: Our findings imply that the downregulation of CYP1A2 expression leads to disorders of lipid metabolism and further leads to lipid droplet accumulation and myelin sheath degeneration, which might ultimately lead to the development of MA. Therefore, our study contributes to promoting the understanding of the molecular mechanisms of MA and providing potential targets for the clinical treatment of MA.

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Stable Rat Model of Mechanical Allodynia in Diabetic Peripheral Neuropathy: The Role of Nerve Compression

Abstract: With the combined use of a latex tube and STZ injection, a stable rat model of painful diabetic peripheral neuropathy (DPN) manifesting both thermal hyperalgesia and mechanical allodynia has been established.

Cited by 8 publications

References 37 publications

<p>Jinmaitong Ameliorates Diabetic Peripheral Neuropathy Through Suppressing TXNIP/NLRP3 Inflammasome Activation In The Streptozotocin-Induced Diabetic Rat Model</p>

<p>Jinmaitong Ameliorates Diabetic Peripheral Neuropathy Through Suppressing TXNIP/NLRP3 Inflammasome Activation In The Streptozotocin-Induced Diabetic Rat Model</p>

Gene Expression Profiling of the Sciatic Nerve in Streptozotocin-Induced Diabetic Rats with Peripheral Neuropathy

Multi-omics analysis revealed the role of CYP1A2 in the induction of mechanical allodynia in type 1 diabetes

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