基于TXNIP/NLRP3炎性小体通路研究芪归通络颗粒对2型糖尿病大鼠坐骨神经的保护作用  

Study on the protective effect of Qigui Tongluo granules on sciatic nerve of type 2 diabetic rats based on TXNIP/NLRP3 inflammasome pathway

作　　者：李金菊 阮诺冰 杨浩[2] 林逸轩 方朝晖[3,4] LI Jinju;RUAN Nuobing;YANG Hao;LIN Yixuan;FANG Zhaohui(First School of Clinical Medicine,Anhui University of Traditional Chinese Medicine,Hefei 230038,China)

机构地区：[1]安徽中医药大学第一临床医学院,安徽合肥230038 [2]安徽中医药大学第二附属医院,安徽合肥230061 [3]安徽中医药大学第一附属医院,安徽合肥230012 [4]安徽省中医药科学院中医药防治糖尿病研究所,安徽合肥230012

出　　处：《陕西中医》2024年第6期733-739,共7页Shaanxi Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(82174153,81774286);安徽省高校协同创新项目(GXXT-2020-025);安徽省高校科研项目(2023AH050867);安徽省合肥综合性国家科学中心大健康研究院项目(2023CXMMTCM003);中央财政转移支付地方项目(2023-24)。

摘　　要：目的:基于硫氧还蛋白相互作用蛋白(TXNIP)/核苷酸结合寡聚化结构域样受体蛋白(NLRP)3炎性小体通路研究芪归通络颗粒对2型糖尿病大鼠坐骨神经的保护作用及潜在机制。方法:90只雄性SD大鼠随机选取10只为空白组,其余大鼠采取高脂饲料喂养联合STZ腹腔注射方法构建2型糖尿病周围神经病变大鼠模型,将造模成功大鼠随机分为模型组、硫辛酸组(60 mg/kg)、芪归通络颗粒高、中、低剂量组,剂量分别为9、4.5、2.25 g/(kg·d)。各给药组给予相应剂量药物灌胃,持续12周。实验过程中观察大鼠一般状态及血糖水平;处死前检测大鼠机械痛阈值(PWMT)和坐骨神经运动传导速度(MNCV);通过酶联免疫吸附试验(ELISA)检测血清炎症因子白介素(IL)-1β、IL-18、IL-6、肿瘤坏死因子-α(TNF-α)、环氧合酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)水平,苏木素-伊红(HE)染色观察坐骨神经形态,Western blot检测坐骨神经组织TXNIP/NLRP3通路相关蛋白表达水平。结果:与空白组相比,模型组大鼠血糖、IL-1β、IL-18、IL-6、TNF-α、COX-2、iNOS明显升高(P<0.05),PWMT和MNCV明显下降(P<0.05),坐骨神经TXNIP、NLRP3、ASC、Caspase-1、IL-1β蛋白相对表达显著上调(P<0.05)。与模型组比较,用药治疗组的PWMT和MNCV明显增加(P<0.05),TXNIP、NLRP3、ASC、Caspase-1、IL-1β蛋白相对表达显著下调(P<0.05),血清IL-1β、IL-18、IL-6、TNF-α、COX-2、iNOS水平下降(P<0.05),坐骨神经病理形态明显改善。结论:芪归通络颗粒可增强2型糖尿病大鼠的坐骨神经功能,改善糖尿病周围神经病变,其潜在作用机制可能与抑制TXNIP/NLRP3炎性小体通路的激活有关。Objective:To investigate the protective effect and potential mechanism of Qigui Tongluo granules on sciatic nerve of type 2 diabetic rats based on the TXNIP/NLRP3 inflammasome pathway.Methods:A total of 90 male SD rats were randomly selected as the blank group,and the rest of the rats were fed with high-fat chow and intraperitoneal injection of STZ to construct a rat model of type 2 diabetic peripheral neuropathy,and were randomly divided into the model group,the alpha lipoic acid group(60 mg/kg),and the Qigui Tongluo granules with high,medium,and low dose group[9,4.5,2.25 g/(kg·d)].Each dosing group was given the corresponding dose of drug by gavage for 12 weeks.The general state and blood glucose level of rats were observed during the experiment,mechanical pain threshold(PWMT)and sciatic nerve motor conduction velocity(MNCV)were detected before execution,serum inflammatory factors interleukin-1β(IL-1β),IL-18,IL-6,TNF-α,COX-2,iNOS were detected by enzyme-linked immunosorbent assay(ELISA)levels,hematoxylin-eosin(HE)staining to observe the morphology of sciatic nerve,and Western blot to detect the expression levels of TXNIP/NLRP3 pathway-related proteins in sciatic nerve tissues.Results:Compared with the blank group,blood glucose,IL-1β,IL-18,IL-6,TNF-α,COX-2,and iNOS were significantly elevated in the model group(P<0.05),PWMT and MNCV were significantly decreased(P<0.05),and the relative expression of sciatic nerve TXNIP,NLRP3,ASC,Caspase-1,and IL-1βproteins was significantly up-regulated(P<0.05).Compared with the model group,the medication intervention groups showed a significant increase in PWMT and MNCV(P<0.05),a significant down-regulation in the relative expression of TXNIP,NLRP3,ASC,Caspase-1,and IL-1βproteins(P<0.05),and a significant decrease in the relative expression of serum IL-1β,IL-18,IL-6,TNF-α,COX-2,and iNOS levels(P<0.05).The pathological morphology of sciatic nerve was significantly improved.Conclusion:Qigui Tongluo granules can enhance sciatic nerve function and improve diabetic periphe

关 键 词：2型糖尿病 芪归通络颗粒 周围神经病变 硫氧还蛋白相互作用蛋白 炎症小体 白介素-1Β 

分 类 号：R587.1[医药卫生—内分泌]