Jinmaitong Ameliorates Diabetic Peripheral Neuropathy Through Suppressing TXNIP/NLRP3 Inflammasome Activation In The Streptozotocin-Induced Diabetic Rat Model
Jinmaitong Ameliorates Diabetic Peripheral Neuropathy Through Suppressing TXNIP/NLRP3 Inflammasome Activation In The Streptozotocin-Induced Diabetic Rat Model
复制标题
DOI：
10.2147/dmso.s223842
复制
发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Liang, Xiaochun
中科院分区：
文献类型：
--
作者：
Sun, Qing;Wang, Chao;Liang, Xiaochun
背景：金脉通（JMT）用于预防和治疗糖尿病周围神经病变（DPN）已有几十年的历史。本研究旨在阐明JMT对链脲佐菌素（STZ）诱导大鼠模型中硫氧还蛋白相互作用蛋白（TXNIP）和nod样受体蛋白3 （NLRP3）炎性体活化的影响。方法：单次腹腔注射STZ 55 mg/ kg，建立糖尿病大鼠模型。将大鼠分为糖尿病对照组、JMT （0.876 g/kg/d）、α -硫辛酸（ALA, 100 mg/kg/d） 3组，每组8 ~ 10只。每4周监测体重和血糖水平，持续12周。采用机械戒断阈值（MWT）试验和Luxol快蓝染色评价坐骨神经机械性异常性痛和髓鞘损伤情况。使用市售试剂盒检测血清t -超氧化物歧化酶（T-SOD）、丙二醛（MDA）和过氧化氢酶（CAT）水平。采用免疫组织化学和Western blot检测TXNIP/NLRP3炎性小体蛋白，包括TXNIP、NLRP3、pro-caspase-1和cleaved -caspase-1，以及下游蛋白白介素(IL)-1 β。Western blot法检测小鼠血清中Gasdermin D （GSDMDC1）蛋白表达，ELISA法检测血清IL-1 β和IL-18水平。结果：治疗后12周，JMT对体重和空腹血糖水平没有显著影响，但改善了SNs的机械异常性疼痛和髓鞘损伤。此外，JMT提高了血清抗氧化酶CAT和T-SOD水平，降低了MDA水平。JMT和ALA均能降低TXNIP、NLRP3和caspase-1蛋白的表达。JMT和ALA也降低了IL-1 β、IL-18和GSDMDC1蛋白的表达。结论：本研究表明TXNIP/NLRP3炎性体激活参与了JMT在stz诱导的糖尿病大鼠模型中保护作用的分子机制，为JMT未来的临床应用提供了新的证据。
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), malon-dialdehyde (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)-1 beta, were measured using immunohistochemistry and Western blot. Gasdermin D (GSDMDC1) protein expression was analyzed using Western blot, and serum IL-1 beta 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-1 beta, 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.