[1]李金菊,阮诺冰,杨 浩,等.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[J].陕西中医,2024,(6):733-739.[doi:DOI:10.3969/j.issn.1000-7369.2024.06.003]
　LI Jinju,RUAN Nuobing,YANG Hao,et al.Study on the protective effect of Qigui Tongluo granules on sciatic nerve of type 2 diabetic rats based on TXNIP/NLRP3 inflammasome pathway[J].,2024,(6):733-739.[doi:DOI:10.3969/j.issn.1000-7369.2024.06.003]
点击复制

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
分享到：

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2024年6期
页码:
733-739
栏目:
基础研究
出版日期:
2024-06-05

文章信息/Info

Title:
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1; 阮诺冰1; 杨 浩2; 林逸轩3; 方朝晖3; 4
(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)
Author(s):
LI Jinju; RUAN Nuobing; YANG Hao; LIN Yixuan; FANG Zhaohui
(First School of Clinical Medicine,Anhui University of Traditional Chinese Medicine,Hefei 230038,China)
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
Keywords:
Type 2 diabetes;  Qigui Tongluo granules;  Peripheral neuropathy;  Thioredoxin-interacting protein;  Inflammasome;  Interleukin-1β
分类号:
R 587.1
DOI:
DOI:10.3969/j.issn.1000-7369.2024.06.003
文献标志码:
A
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。
Abstract:
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-1β proteins 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-1β proteins(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 peripheral neuropathy in T2DM rats,its potential mechanism of action may be related to the inhibition of the activation of TXNIP/NLRP3 inflammasome pathway.

参考文献/References:

[1] SELVARAJAH D,KAR D,KHUNTI K,et al.Diabetic peripheral neuropathy:Advances in diagnosis and strategies for screening and early intervention[J].Lancet Diabetes Endocrinol,2019,7(12):938-948.
[2] 王芸,高丽娟,胡淑国,等.复方丹参滴丸改善2型糖尿病早期周围神经病变的效果观察[J].河北医药,2018,40(7):999-1002,1007.
[3] JENDE J M,GROENER J B,OIKONOMOU D,et al.Diabetic neuropathy differs between type 1 and type 2 diabetes:Insights from magnetic resonance neurography[J].Ann Neurol,2018,83(3):588-598.
[4] ELAFROS M A,ANDERSEN H,BENNETT D L,et al.Towards prevention of diabetic peripheral neuropathy:Clinical presentation,pathogenesis,and new treatments[J].Lancet Neurol,2022,21(10):922-936.
[5] YANG K,WANG Y,LI Y W,et al.Progress in the treatment of diabetic peripheral neuropathy[J].Biomed Pharmacother,2022,148:112717.
[6] 李艳飞,王晶,陈定章,等.下肢神经剪切波弹性成像对不同程度糖尿病周围神经病变的诊断效能分析[J].陕西医学杂志,2022,51(9):1102-1105.
[7] 杨鹏,张程斐,张亚奇,等.p38 MAPK通路在糖尿病周围神经病变中的作用及中药干预的研究进展[J].中国实验方剂学杂志,2023,29(9):99-108.
[8] 姜志妮,牛云飞,方朝晖.益气活血通络方对糖尿病周围神经病变患者血清TNF-α、IL-10、CD40及CD40L的影响[J].实用中西医结合临床,2021,21(16):121-124.
[9] 曹雯,莫凯,潘金凤,等.中医药调控TXNIP/NLRP3信号通路防治疾病的研究进展[J].广西医学,2023,45(8):973-977.
[10] HAN L,XI G,GUO N,et al.Expression and mechanism of TXNIP/NLRP3 inflammasome in sciatic nerve of type 2 diabetic rats[J].Dis Markers,2022,2022:9696303.
[11] 汪峰,杨国珍,刘宓,等.链脲佐菌素诱导的糖尿病大鼠模型稳定性观察[J].贵阳医学院学报,2012,37(1):40-42.
[12] JOLIVALT C G,FRIZZI K E,GUERNSEY L,et al.Peripheral neuropathy in mouse models of diabetes[J].Curr Protoc Mouse Biol,2016,6(3):223-255.
[13] 杨丹,崔雅忠,张倩,等.1型与2型糖尿病大鼠周围神经病变的比较[J].基础医学与临床,2019,39(1):27-31.
[14] 姚鸿萍,封卫毅,魏友霞,等.大鼠坐骨神经传导速度测定的方法学考察[J].中国药房,2011,22(1):18-20.
[15] 金晓丹,余江毅.从湿瘀论治消渴痹证[J].陕西中医,2021,42(5):629-631.
[16] 庞国明,孙扶,谢卫平,等.中医药治疗糖尿病周围神经病变临床研究进展[J].世界中西医结合杂志,2020,15(12):2339-2342.
[17] 魏萱.中医药治疗糖尿病周围神经病变研究进展[J].河北中医,2023,45(7):1203-1207.
[18] 王秀阁,倪青,庞国明.糖尿病周围神经病变病证结合诊疗指南[J].中医杂志,2021,62(18):1648-1656.
[19] 薛丽,韩红,张力.桑黄素通过抑制TXNIP/NLRP3/Caspase-1信号通路对脑缺血再灌注大鼠神经元凋亡的影响[J].天津医药,2023,51(5):487-491.
[20] 范咸玉,邹建文,陈旭,等.基于TXNIP/NLRP3炎性小体通路研究清热凉血方对溃疡性结肠炎大鼠肠黏膜屏障的保护作用[J].中国老年学杂志,2023,43(18):4563-4567.
[21] 曹钦钰,王彦,杨芳,等.热淋清颗粒对慢性尿路感染模型大鼠TXNIP/NLRP3炎症小体通路及免疫状态的影响[J].中国免疫学杂志,2023,39(6):1269-1273.
[22] 刘华亭,郑博文,陈晨,等.基于NLRP3/Caspase-1/IL-1β信号通路探讨复方蛇龙胶囊对膜性肾病大鼠的作用[J].陕西中医,2023,44(6):709-716.
[23] YU Z W,ZHANG J,LI X,et al.A new research hot spot:The role of NLRP3 inflammasome activation,a key step in pyroptosis,in diabetes and diabetic complications[J].Life Sciences,2020,240:117138.
[24] ICEL E,ICEL A,UCAK T,et al.The effects of lycopene on alloxan induced diabetic optic neuropathy[J].Cutaneous and Ocular Toxicology,2019,38(1):88-92.
[25] SWANSON K V,DENG M,TING J P.The NLRP3 inflammasome:Molecular activation and regulation to therapeutics[J].Nature Reviews Immunology,2019,19(8):477-489.
[26] WANG W W,HAN W B,WAN Y G,et al.Molecular regulative mechanisms of NLRP3 inflammasome activation in diabetic nephropathy and interventional effects of Chinese herbal medicine[J].China Journal of Chinese Materia Medica,2020,45(1):7-13.
[27] 张静雯,王利,赵敏,等.核苷酸结合寡聚化结构域样受体蛋白3介导细胞焦亡在痛风性关节炎中的作用机制研究[J].陕西医学杂志,2022,51(5):561-565.
[28] 宋艳琦,安丽丽,霍永利,等.芍药汤联合美沙拉嗪对湿热型溃疡性结肠炎大鼠NF-κB、COX-2、MCP-1的影响研究[J].时珍国医国药,2021,32(3):570-574.
[29] CHAN P C,LIAO M T,HSIEH P S.The dualistic effect of COX-2-mediated signaling in obesity and insulin resistance[J].Int J Mol Sci,2019,20(13):3115.
[30] AKBAR S,SUBHAN F,AKBAR A,et al.Targeting anti-inflammatory pathways to treat diabetes-induced neuropathy by 6-hydroxy flavanone[J].Nutrients,2023,15(11):2552.
[31] YANIK B M,DAUCH J R,CHENG H T.Interleukin-10 reduces neurogenic inflammation and pain behavior in a mouse model of type 2 diabetes[J].J Pain Res,2020,13:3499-3512.
[32] NASIRY D,KHALATBARY A R,AHMADVAND H,et al.Protective effects of methanolic extract of Juglans regia leaf on streptozotocin-induced diabetic peripheral neuropathy in rats[J].BMC Complement Altern Med,2017,17(1):476.

相似文献/References:

[1]李向辉,卢文杰.葛黄降糖汤治疗2型糖尿病合并颈动脉硬化临床研究*[J].陕西中医,2019,(5):580.
　LI Xianghui,LU Wenjie..Effect of Gehuang Jiangtang decoction on mellitus complicated with carotid arteriosclerosis in type 2 diabetes patients[J].,2019,(6):580.
[2]杨斯皓,马方霞,詹 云.一贯煎合六味地黄汤配合西药治疗2型糖尿病合并非酒精性脂肪肝临床疗效及对患者生活质量的评价*[J].陕西中医,2019,(8):1006.
　YANG Sihao,MA Fangxia,ZHAN Yun..Clinical efficacy and quality of life evaluation of Yiguanjian plus Liuwei Dihuang decoction with western medicine in the treatment of type 2 diabetes with nonalcoholic fatty liver disease[J].,2019,(6):1006.
[3]孙晓红,陈学彬△.芪精丹兰汤对伴有左心室舒张功能不全的2型糖尿病合并代谢综合征患者糖脂代谢、心率变异性的影响*[J].陕西中医,2019,(10):1336.
　SUN Xiaohong,CHEN Xuebin..Effect of Qijing Danlan decoction on glucose and lipid metabolism and heart rate variability in patients with type 2 diabetes mellitus complicated with MS with left ventricular diastolic dysfunction[J].,2019,(6):1336.
[4]訾 璐,胡小军△,王 玉,等.针刺中脘穴联合自拟茶方对2型糖尿病患者血糖水平的影响*[J].陕西中医,2019,(10):1460.
　ZI Lu,HU Xiaojun,WANG Yu,et al.Effect of zhong wan acupuncture combined with selfdesigned tea prescription on blood glucose level in patients with type 2 diabetes mellitus[J].,2019,(6):1460.
[5]文启友,周 伶,马若梦,等.化瘀利尿法论治2型糖尿病探析[J].陕西中医,2021,(6):761.[doi:DOI:10.3969/j.issn.1000-7369.2020.06.021]
[6]谢兆桃,周卓宁,郑 鹏,等.从中焦论治2型糖尿病患者餐后血糖波动[J].陕西中医,2021,(6):764.[doi:DOI:10.3969/j.issn.1000-7369.2020.06.022]
[7]胡全穗,伍宗明.运用中药药对配伍优化消渴病中医防治方案临床研究[J].陕西中医,2021,(8):1084.[doi:DOI:10.3969/j.issn.1000-7369.2020.08.024]
　HU Quansui,WU Zongming.Clinical research on optimizing the TCM prevention and treatment of Xiaoke by using compatibility of herb-partners[J].,2021,(6):1084.[doi:DOI:10.3969/j.issn.1000-7369.2020.08.024]
[8]卢 昉,刘晓霞,梁佩玲,等.清热益气降糖方对2型糖尿病患者胰岛α、β细胞功能的影响[J].陕西中医,2021,(10):1400.[doi:DOI:10.3969/j.issn.1000-7369.2020.10.019]
[9]刘厚利,呼兴华,何 莉,等.基于数据挖掘许建秦治疗湿热内蕴型糖尿病用药规律分析[J].陕西中医,2021,(10):1455.[doi:DOI:10.3969/j.issn.1000-7369.2020.10.035]
[10]陈继玲,任珍珍,王劭敏,等.玉泉丸合生脉散联合二甲双胍治疗气阴两虚证2型糖尿病临床研究[J].陕西中医,2021,(11):1553.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.013]
　CHEN Jiling,REN Zhenzhen,WANG Shaomin,et al.Efficacy of Yuquan pills with Shengmai powder and metformin tablets in the treatment of T2DM with deficiency of Qi and Yin[J].,2021,(6):1553.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.013]

备注/Memo

备注/Memo:
基金项目: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)
更新日期/Last Update: 2024-06-11