Tangbikang Granules Modulates AMPK/NF-<italic style="font-style: italic">κ</italic>B Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats

BAI Huizhong; QIN Lingling; ZHANG Yaqi; ZHANG Chengfei; ZHANG Qiue; ZUO Xinwei; LIU Gang; ZHAO Yu; ZHAO Yi; LIU Tonghua; MU Xiaohong

doi:10.13422/j.cnki.syfjx.20230723

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Tangbikang Granules Modulates AMPK/NF-κB Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats

更新时间：2023-03-30

- Tangbikang Granules Modulates AMPK/NF-κB Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 29, Issue 9, Pages: 91-98(2023)
- 作者机构：
  
  1.北京中医药大学东直门医院，北京 100700
  2.北京中医药大学科技处，北京 100029
  3.教育部高等学校学科创新引智基地，北京 100029
  4.北京中医药大学生命科学学院，北京 100029
  5.北京中医药大学中医学院，北京 100029
  6.北京中医药大学中医养生学北京市重点实验室，北京 100029
  7.科技部中医药防治糖尿病国际联合研究中心，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20230723
  CLC： R2-0;R22;R242;R2-031;R285.5
- Published：05 May 2023，
  
  Published Online：01 February 2023，
  
  Received：26 September 2022，
- 稿件说明：
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白惠中,秦灵灵,张亚奇等.糖痹康颗粒调控AMPK/NF-κB通路改善糖尿病大鼠坐骨神经炎症反应[J].中国实验方剂学杂志,2023,29(09):91-98.

BAI Huizhong,QIN Lingling,ZHANG Yaqi,et al.Tangbikang Granules Modulates AMPK/NF-κB Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(09):91-98.
白惠中,秦灵灵,张亚奇等.糖痹康颗粒调控AMPK/NF-κB通路改善糖尿病大鼠坐骨神经炎症反应[J].中国实验方剂学杂志,2023,29(09):91-98. DOI： 10.13422/j.cnki.syfjx.20230723.

BAI Huizhong,QIN Lingling,ZHANG Yaqi,et al.Tangbikang Granules Modulates AMPK/NF-κB Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats[J].Chinese Journal of Experimental Traditional Medical Formulae,2023,29(09):91-98. DOI： 10.13422/j.cnki.syfjx.20230723.

摘要

目的

探讨糖痹康颗粒通过调控腺苷活化蛋白激酶/核转录因子-

B（AMPK/NF-

B）通路对糖尿病大鼠坐骨神经炎症的影响。

方法

SD大鼠高脂高糖饲料诱导连续8周后按单次35 mg·kg

-1

链脲佐菌素（STZ）腹腔注射造模。成模后按体质量、血糖随机将大鼠分为模型组和各给药组、糖痹康颗粒低、中、高剂量组（0.625、1.25、2.5 g·kg

-1

）及硫辛酸组（0.026 8 g·kg

-1

），并设正常组。成模后持续给药干预12周。期间分别检测治疗前及治疗第4、8、12周大鼠的体质量、血糖水平及热痛阈；于给药第12周时取材坐骨神经进行苏木素-伊红（HE）、劳克坚牢蓝（LFB）染色，扫描电镜观察坐骨神经超微结构变化；酶联免疫吸附测定法（ELISA）检测坐骨神经中白细胞介素-1

（IL-1

）、肿瘤坏死因子-

（TNF-

）表达水平；蛋白免疫印迹法（Western blot）检测大鼠坐骨神经组织中AMPK、磷酸化（p）-AMPK、NF-

B的蛋白表达水平。

结果

与正常组比较，模型组大鼠造模后各时间点血糖浓度、热痛阈均显著升高（

0.01）；坐骨神经IL-1

、TNF-

水平及NF-

B蛋白表达显著升高（

0.01），p-AMPK/AMPK蛋白表达显著降低（

0.01）。经糖痹康颗粒治疗后，与模型组比较，糖痹康颗粒各组热痛阈明显降低（

0.05，

0.01），坐骨神经IL-1

、TNF-

水平及NF-

B蛋白表达明显降低（

0.05，

0.01）；糖痹康颗粒高、中剂量组p-AMPK/AMPK蛋白表达明显升高（

0.05，

0.01）。坐骨神经形态学观察显示，糖痹康颗粒治疗后大鼠坐骨神经排列整齐度、致密程度、脱髓鞘变化均优于模型组。

结论

糖痹康颗粒可以改善糖尿病大鼠坐骨神经功能、减轻神经炎症损伤，其作用机制可能与上调AMPK/NF-

B通路中AMPK的表达，抑制下游NF-

B表达，从而减轻因NF-

B激活引起IL-1

、TNF-

等炎症因子升高造成的神经炎症反应相关。

Abstract

Objective

To explore the effect of Tangbikang granules （TBK） on sciatic nerve inflammation in diabetic rats through modulation of adenosine monophosphate-activated protein kinase （AMPK）/nuclear factor （NF）-

B pathway.

Method

SD rats were fed with high-fat and high-sugar diet for 8 weeks and then treated with streptozotocin （STZ，

） at 35 mg·kg

-1

for modeling. Then the rats were randomized into diabetes group， low-dose （0.625 g·kg

-1

）， medium-dose （1.25 g·kg

-1

）， and high-dose （2.5 g·kg

-1

） TBK groups， and lipoic acid group （0.026 8 g·kg

-1

） according to body weight and blood glucose level， and a normal group was designed. After modeling， administration began and lasted 12 weeks. The body mass， blood glucose level， and thermal withdrawal latency （TWL） of the rats were detected before treatment and at the 4

， 8

， and 12

week of administration. At the 12

week， the sciatic nerve was collected for hematoxylin-eosin （HE） and Luxol fast blue （LFB） staining， and the structural changes of sciatic nerve were observed under scanning electron microscope. The levels of interleukin-1

（IL-1

） and tumor necrosis factor-

（TNF-

） in sciatic nerve were measured by enzyme-linked immunosorbent assay （ELISA）， and the levels of AMPK， phosphorylated （p）-AMPK， and NF-

B proteins in the sciatic nerve were measured by Western blot.

Result

The blood glucose concentration and TWL in the model group were higher than those in the normal group at each time point （

0.01）. The levels of IL-1

， TNF-

， and NF-

B protein in sciatic nerve in the model group were higher than those in the normal group （

0.01）， and the p-AMPK/AMPK ratio was smaller than that in the normal group （

0.01）. Compared with the model group， TBK of the three doses lowered the TWL （

0.05，

0.01） and the levels of IL-1

， TNF-

， and NF-

B protein in sciatic nerve of rats （

0.05，

0.01）， and high-dose and medium-dose TBK raised p-AMPK/AMPK （

0.05，

0.01）. The sciatic nerve fibers were orderly and compact with alleviation of demyelination in rats treated with TBK compared with those in the model group.

Conclusion

TBK improves the function of sciatic nerve and alleviates neuroinflammation in diabetic rats. The mechanism is the likelihood that it up-regulates the expression of AMPK in the AMPK/NF-

B pathway and inhibits the expression of downstream NF-

B， thereby alleviating the neuroinflammation caused by high levels of inflammatory factors such as IL-1

and TNF-

due to NF-

B activation.

关键词

糖痹康颗粒核转录因子-κB（NF-κB）腺苷活化蛋白激酶（AMPK）糖尿病周围神经病变动物实验坐骨神经炎症

Keywords

Tangbikang granulesnuclear factor-κB （NF-κB）adenosine monophosphate-activated protein kinase （AMPK）diabetic peripheral neuropathyanimal experimentsnerveinflammation

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Related Institution

Beijing University of Chinese Medicine

College of Traditional Chinese Medicine （TCM）， Beijing University of Chinese Medicine

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The Affiliated Hospital of Jiangxi University of Chinese Medicine

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Tangbikang Granules Modulates AMPK/NF-κB Pathway to Alleviate Sciatic Nerve Inflammation in Diabetic Rats

DOI：10.13422/j.cnki.syfjx.20230723

摘要

Abstract

关键词

Keywords

references