[1]王三强,王 磊,许敏光,等.基于TLR4/MyD88/NF-κB通路探究桃红四物汤对糖尿病周围神经病变大鼠炎症反应的影响[J].陕西中医,2023,(6):683-687.[doi:DOI:10.3969/j.issn.1000-7369.2023.06.001]
　WANG Sanqiang,WANG Lei,XU Minguang,et al.Effect of Taohong Siwu decoction on inflammatory response in diabetic peripheral neuropathy rats based on TLR4/MyD88/NF-κB pathway[J].,2023,(6):683-687.[doi:DOI:10.3969/j.issn.1000-7369.2023.06.001]
点击复制

基于TLR4/MyD88/NF-κB通路探究桃红四物汤对糖尿病周围神经病变大鼠炎症反应的影响
分享到：

《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2023年6期
页码:
683-687
栏目:
基础研究
出版日期:
2023-06-05

文章信息/Info

Title:
Effect of Taohong Siwu decoction on inflammatory response in diabetic peripheral neuropathy rats based on TLR4/MyD88/NF-κB pathway
作者:
王三强1; 王 磊1; 许敏光1; 杨田野2; 冯宝佺1
(1.火箭军特色医学中心,北京100088; 2.北京市西城区广外医院,北京 100055)
Author(s):
WANG Sanqiang; WANG Lei; XU Minguang; YANG Tianye; FENG Baoquan
(Rocket Army Medical Center,Beijing 100088,China)
关键词:
糖尿病周围神经病变;  桃红四物汤;  炎症因子;  神经传导;  Toll样受体4;  髓样分化因子88;  核转录因子kappa B通路
Keywords:
Diabetic peripheral neuropathy;  Taohong Siwu decoction;  Inflammatory factors;  Nerve conduction;  Toll-like receptor 4;  Myeloid differentiation factor 88;  Nuclear factor kappa B pathway
分类号:
R 587.2
DOI:
DOI:10.3969/j.issn.1000-7369.2023.06.001
文献标志码:
A
摘要:
目的:探究桃红四物汤对糖尿病周围神经病变(DPN)大鼠炎症反应及对Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核转录因子kappan B(NF-κB)通路的影响。方法:从45只SD大鼠中随机选取10只为对照组,其余35只大鼠建立DPN模型,3只大鼠建模失败,其余随机分为模型组,桃红四物汤低、高剂量组及α-硫辛酸组,每组各8只。桃红四物汤低、高剂量组分别给予4.5、18 g/(kg·d)的桃红四物汤,α-硫辛酸组给予α-硫辛酸20 mg/(kg·d),对照组及模型组给予等量的0.9%氯化钠溶液,均灌胃给药。连续给药8周后,检测大鼠血清炎症因子、血糖及血脂指标及神经传导情况,观察坐骨神经病理学变化,检测TLR4相关通路蛋白表达情况。结果:与对照组比较,模型组血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)及白细胞介素-6(IL-6)水平升高,血糖、糖化血红蛋白(HbA1c)、甘油三酯(TG)及血清总胆固醇(TC)水平升高,感觉神经传导速度(SNCV)及运动神经传导速度(MNCV)水平降低,TLR4、MyD88、NF-κB蛋白表达上调(P<0.05); 与模型组比较,桃红四物汤低、高剂量组及α-硫辛酸组血清TNF-α、IL-1β及IL-6水平降低,血糖、HbA1c、TG及TC水平降低,SNCV、MNCV水平升高,TLR4、MyD88、NF-κB蛋白表达下调(P<0.05); 与桃红四物汤低剂量组比较,桃红四物汤高剂量组及α-硫辛酸组血清TNF-α、IL-1β及IL-6水平降低,血糖、HbA1c、TG及TC水平降低,SNCV、MNCV水平升高,TLR4、MyD88、NF-κB蛋白表达下调(P<0.05); 与桃红四物汤高剂量组比较,α-硫辛酸组血清TNF-α、IL-1β及IL-6水平降低,血糖、HbA1c、TG及TC水平降低,SNCV、MNCV水平升高,TLR4、MyD88、NF-κB蛋白表达下调(P<0.05)。结论:桃红四物汤能够改善DPN大鼠炎症反应指标及血糖血脂水平,提高神经传导速度,对坐骨神经起到保护作用,其作用机制可能与抑制TLR4/MyD88/NF-κB通路有关。
Abstract:
Objective:To explore the effect of Taohong Siwu decoction on inflammatory response and TLR4/MyD88/NF-κB pathway in diabetic peripheral neuropathy(DPN)rats.Methods:Ten rats were randomly selected from 45 SD rats as the control group,and the remaining 35 rats were used to establish the DPN model.Three rats failed to establish the model,and the rest were randomly divided into four groups:model group,low-dose and high-dose Taohong Siwu decoction group,and α-lipoic acid group,with eight rats in each group.The low-dose and high-dose groups were given 4.5,18 g/(kg·d)of Taohong Siwu decoction respectively,the α-lipoic acid group was given 20 mg/(kg·d)of α-lipoic acid,and the control group and model group were given equal amounts of saline,all by gavage.After continuous administration for 8 weeks,serum inflammatory factors,blood glucose and blood lipid indicators,nerve conduction status were detected in rats.The pathological changes of sciatic nerve were observed,and the expression of TLR4-related pathway proteins was detected.Results:Compared with the control group,serum TNF-α,IL-1β and IL-6 levels increased in model group,blood glucose,HbA1c,TG and TC levels increased,SNCV and MNCV levels decreased,TLR4,MyD88,NF-κB protein expression up-regulated(P<0.05).Compared with model group,serum TNF-α,IL-1β,IL-6 levels decreased in low-dose,high-dose Taohong Siwu decoction groups,and α-lipoic acid group,blood glucose,HbA1c,TG,TC levels decreased,SNCV,MNCV levels increased,TLR4,MyD88,NF-κB protein expression down-regulated(P<0.05).Compared with low-dose Taohong Siwu decoction group,serum TNF-α,IL-1β,IL-6 levels decreased in high-dose Taohong Siwu decoction groups,and α-lipoic acid group,blood glucose,HbA1c,TG,TC levels decreased,SNCV,MNCV levels increased,TLR4,MyD88,NF-κB protein expression down-regulated(P<0.05).Compared with high-dose Taohong Siwu decoction groups,serum TNF-α,IL-1β,IL-6 levels decreased in α-lipoic acid group,blood glucose,HbA1c,TG,TC levels decreased,SNCV,MNCV levels increased,TLR4,MyD88,NF-κB protein expression down-regulated(P<0.05).Conclusion:Taohong Siwu decoction can improve inflammatory response indicators,blood glucose and blood lipid levels in DPN rats,increase nerve conduction velocity,protect sciatic nerve,which may be related to TLR4/MyD88/NF-κB pathway.

参考文献/References:

[1] Sloan G,Selvarajah D,Tesfaye S.Pathogenesis,diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy[J].Nat Rev Endocrinol,2021,17(7):400-420.
[2] Roikjer J,Morch CD,Ejskjaer N.Diabetic peripheral neuropathy:Diagnosis and treatment[J].Curr Drug Saf,2021,16(1):2-16.
[3] Baum P,Toyka KV,Bluher M,et al.Inflammatory mechanisms in the pathophysiology of diabetic peripheral neuropathy(DN)-new aspects[J].Int J Mol Sci,2021,22(19):10835.
[4] 崔 志,蔡 华,马淑红,等.芪明颗粒联合西药治疗糖尿病周围神经病变临床研究[J].陕西中医,2021,42(3):312-314.
[5] 孙 建,刘新宇.三七总皂苷胶囊治疗糖尿病周围神经病变临床疗效及机制研究[J].陕西医学杂志,2020,49(11):1496-1498,1506.
[6] 王 越,原 霞,郭姗姗.温针灸联合穴位埋线治疗糖尿病周围神经病变[J].吉林中医药,2022,42(7):850-853.
[7] 章梦玲,蔡 明,夏文文,等.桃红四物汤对糖尿病脑病大鼠认知功能的保护作用[J].安徽中医药大学学报,2022,41(3):64-70.
[8] 张 阳,王 琴,朱 勤,等.陈洪宇基于“乙癸同源,肝肾共治”理论治疗糖尿病肾病的经验[J].浙江中医药大学学报,2022,46(1):28-32.
[9] 屈 璐,候胜开,高楠楠,等.糖尿病周围神经病变大鼠模型制作的实验研究[J].贵州医科大学学报,2017,42(1):60-63.
[10] 黄继汉,黄晓晖,陈志扬,等.药理试验中动物间和动物与人体间的等效剂量换算[J].中国临床药理学与治疗学,2004,9(9):1069-1072.
[11] 孙 晶.当归四逆汤联合甲钴胺对糖尿病周围神经病变大鼠坐骨神经SNCV、MNCV、NGF及TrkA的影响[D].大连:大连医科大学,2018.
[12] 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.
[13] 何 欢,李春晖,李鸣镝.糖痛方对糖尿病周围神经病变模型大鼠坐骨神经PI3K、Akt、mTOR表达的影响[J].国际中医中药杂志,2022,44(1):43-48.
[14] 樊家乙,阴兆辉,富颖超,等.桃红四物汤合自拟补气养阴汤联合西医常规疗法治疗糖尿病足气阴两虚兼瘀证患者42例临床观察[J].中医杂志,2022,63(17):1668-1672.
[15] 周 密,姚伟洁.木丹颗粒对糖尿病周围神经病变大鼠TLR4相关通路的调控作用研究[J].西部中医药,2021,34(10):52-56.
[16] 李逸潇,王利莹,郭宇鑫,等.糖络宁对糖尿病周围神经病变大鼠背根神经节Toll样受体2/4的影响[J].中国医药导报,2020,17(13):37-40.
[17] 李文婷,郑舒宁,张 琪,等.基于网络药理学探讨黄芪-川芎药对对糖尿病周围神经病变作用机制的研究[J].上海中医药杂志,2021,55(1):6-12,34.
[18] 王倩倩,刘永惠,王 蒙,等.基于网络药理学探讨桃红四物汤治疗糖尿病周围神经病变作用机制[J].陕西中医,2022,43(9):1305-1309.
[19] Pang B,Qiao L,Wang S,et al.MiR-214-3p plays a protective role in diabetic neuropathic rats by regulating Nav1.3 and TLR4[J].Cell Biol Int,2021,45(11):2294-2303.
[20] Aghamiri SH,Komlakh K,Ghaffari M.The crosstalk among TLR2,TLR4 and pathogenic pathways:A treasure trove for treatment of diabetic neuropathy[J].Inflammopharmacology,2022,30(1):51-60.

相似文献/References:

[1]徐 磊,李 骥,梁志强,等.知葛通脉颗粒治疗糖尿病周围神经病变临床研究*[J].陕西中医,2019,(8):1049.
　XU Lei,LI Ji,LIANG Zhiqiang,et al.Clinical efficacy of Zhige Tongmai granules for treating diabetic peripheral neuropathy[J].,2019,(6):1049.
[2]苏虹霞,宋宗良△,段玉红,等.芪藤通痹散熏洗治疗糖尿病周围神经病变临床观察*[J].陕西中医,2019,(10):1386.
　SU Hongxia,SONG Zongliang,DUAN Yuhong,et al.Clinical study of Qiteng Tongbi san fumigation and washing on the treatment of diabetic peripheral neuropathy[J].,2019,(6):1386.
[3]戴 琴,徐 骁△.温阳活血方治疗糖尿病周围神经病变临床研究[J].陕西中医,2020,(1):70.
[4]王银庄,张继东,刘 磊.桃红四物汤化裁治疗稳定型心绞痛合并心力衰竭临床研究*[J].陕西中医,2020,(5):625.[doi:DOI:10.3969/j.issn.10007369.2020.05.020]
　WANG Yinzhuang,ZHANG Jidong,LIU Lei..Effect of Taohong Siwu decoction on stable angina pectoris with heart failure[J].,2020,(6):625.[doi:DOI:10.3969/j.issn.10007369.2020.05.020]
[5]周海娟,周学林,邱晓堂.周学林教授治疗阳虚寒凝型糖尿病周围神经病变经验*[J].陕西中医,2020,(11):1651.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.035]
　ZHOU Haijuan,ZHOU Xuelin,QIU Xiaotang..Professor ZHOU Xueli's clinical experience on Wenjing Tongluo decoction on diabetic peripheral neuropathy[J].,2020,(6):1651.[doi:DOI:10.3969/j.issn.1000-7369.2020.11.035]
[6]崔 志,蔡 华,马淑红,等.芪明颗粒联合西药治疗糖尿病周围神经病变临床研究[J].陕西中医,2021,(3):312.[doi:DOI:10.3969/j.issn.1000-7369.2020.03.010]
　CUI Zhi,CAI Hua,MA Shuhong,et al.Clinical study of Qiming granule combined with western medicine on diabetic peripheral neuropathy[J].,2021,(6):312.[doi:DOI:10.3969/j.issn.1000-7369.2020.03.010]
[7]杨 冰,马国斌.降糖祛瘀汤联合α-硫辛酸治疗气阴两虚兼血瘀型2型糖尿病并发周围神经病变临床研究[J].陕西中医,2021,(4):493.[doi:DOI:10.3969/j.issn.1000-7369.2020.04.023]
[8]孙建娟,吴光秀,令狐昌敏,等.参芪降糖颗粒治疗糖尿病周围神经病变临床研究[J].陕西中医,2021,(7):893.[doi:DOI:10.3969/j.issn.1000-7369.2020.07.021]
[9]覃祚海,马成豪,王 浩,等.桃红四物汤对全膝关节置换术后患者转化生长因子信号通路及骨愈合的影响[J].陕西中医,2021,(9):1243.[doi:DOI:10.3969/j.issn.1000-7369.2020.09.024]
　QIN Zuohai,MA Chenghao,WANG Hao,et al.Taohong Siwu decoction for transforming growth factor-β signal pathway and bone healing in patients with total knee arthroplasty[J].,2021,(6):1243.[doi:DOI:10.3969/j.issn.1000-7369.2020.09.024]
[10]蒋 旭,胡 勇,程松苗,等.桃红四物汤合五苓散加减治疗对前交叉韧带重建术后早期膝关节肿胀、疼痛及关节功能康复的影响[J].陕西中医,2021,(10):1416.[doi:DOI:10.3969/j.issn.1000-7369.2020.10.023]
　JIANG Xu,HU Yong,CHENG Songmiao,et al.Effect of modified Taohong Siwu decoction combined with Wuling powder on early joint knee swelling,pain and joint function rehabilitation after anterior cruciate ligament reconstruction[J].,2021,(6):1416.[doi:DOI:10.3969/j.issn.1000-7369.2020.10.023]
[11]王倩倩,刘永惠,王 蒙,等.基于网络药理学探讨桃红四物汤治疗糖尿病周围神经病变作用机制[J].陕西中医,2022,(9):1305.[doi:DOI:10.3969/j.issn.1000-7369.2022.09.039]
　WANG Qianqian,LIU Yonghui,WANG Meng,et al.Mechanism of Taohong Siwu decoction in treatment of diabetic peripheral neuropathy based on network pharmacology[J].,2022,(6):1305.[doi:DOI:10.3969/j.issn.1000-7369.2022.09.039]

备注/Memo

备注/Memo:
基金项目:国家自然科学基金资助项目(81202637)
更新日期/Last Update: 2023-06-09