Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1<italic style="font-style: italic">α</italic>/SIRT3 Signaling Pathway

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

doi:10.13422/j.cnki.syfjx.20231327

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Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway

更新时间：2024-02-04

- Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 30, Issue 6, Pages: 75-82(2024)
- 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，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.北京中医药大学教育部中医养生学重点实验室，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.20231327
  CLC： R22;R242;R2-031;R285.5
- Received：17 March 2023，
  
  Published Online：08 June 2023，
  
  Published：20 March 2024
- 稿件说明：
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刘港,张亚奇,秦灵灵等.糖痹康颗粒调控AMPK/PGC-1α/SIRT3信号通路抑制糖尿病大鼠坐骨神经氧化应激反应[J].中国实验方剂学杂志,2024,30(06):75-82.

LIU Gang,ZHANG Yaqi,QIN Lingling,et al.Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(06):75-82.
刘港,张亚奇,秦灵灵等.糖痹康颗粒调控AMPK/PGC-1α/SIRT3信号通路抑制糖尿病大鼠坐骨神经氧化应激反应[J].中国实验方剂学杂志,2024,30(06):75-82. DOI： 10.13422/j.cnki.syfjx.20231327.

LIU Gang,ZHANG Yaqi,QIN Lingling,et al.Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(06):75-82. DOI： 10.13422/j.cnki.syfjx.20231327.

摘要

目的

探讨糖痹康颗粒通过调节腺苷酸活化蛋白激酶/过氧化物酶体增殖物激活受体

共激活因子-1

/线粒体Sirtuins3（AMPK/PGC-1

/SIRT3）信号通路对糖尿病大鼠坐骨神经氧化应激的影响。

方法

采用ZDF大鼠建立自发性肥胖型2型糖尿病模型。成模后随机分为糖痹康颗粒高、中、低剂量组（2.5、1.25、0.625 g·kg

-1

·d

-1

）及硫辛酸组（0.026 8 g·kg

-1

·d

-1

），并设立正常组。成模后持续给药干预12周。分别检测干预前及干预后第4、8、12周大鼠血糖。第12周检测各组大鼠运动神经传导速度（MNCV）、感觉神经传导速度（SNCV）、神经血流速度、机械痛阈及热痛阈并取材坐骨神经进行苏木素-伊红（HE）染色观察组织形态；透射电镜观察坐骨神经超微结构变化；酶联免疫吸附测定法（ELISA）检测坐骨神经中超氧化物歧化酶（SOD）、丙二醛（MDA）、白细胞介素-1

（IL-1

）、肿瘤坏死因子-

（TNF-

）表达水平；实时荧光定量聚合酶链式反应（Real-time PCR）检测大鼠坐骨神经组织AMPK

、AMPK

、PGC-1

、SIRT3 mRNA表达。

结果

与正常组比较，模型组大鼠各时间点空腹血糖升高（

0.01），机械痛阈降低（

0.05），热板潜伏时间延长（

0.01），MNCV、SNCV、神经血流速度减慢（

0.05），SOD表达降低（

0.01），MDA、IL-1

、TNF-

表达升高（

0.01），AMPK

、AMPK

、PGC-1

、SIRT3 mRNA表达均降低（

0.01）；模型组大鼠坐骨神经纤维结构松散、排列混乱、脱髓鞘改变明显。与模型组比较，糖痹康颗粒高剂量组大鼠在干预8、12周空腹血糖降低（

0.01），机械痛阈升高（

0.05），热板潜伏时间缩短（

0.01），MNCV、SNCV、神经血流速度（Flux）增快（

0.05），SOD表达升高（

0.01），MDA、IL-1

、TNF-

表达降低（

0.01），AMPK

、AMPK

、PGC-1

、SIRT3 mRNA表达升高（

0.01）；糖痹康颗粒高剂量组大鼠坐骨神经纤维结构更紧密、排列更整齐，仅有少部分脱髓鞘改变。糖痹康颗粒高、中、低剂量组有明显的量效趋势。

结论

糖痹康颗粒可能部分通过调控AMPK/PGC-1

/SIRT3信号通路发挥抗氧化应激作用，改善糖尿病大鼠坐骨神经功能。

Abstract

Objective

To investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor

coactivator-1

/mitochondrial Sirtuins 3 （AMPK/PGC-1

/SIRT3） signaling pathway.

Method

The spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling， they were randomly divided into high， medium， and low dose Tangbikang granule groups （2.5， 1.25， 0.625 g·kg

-1

·d

-1

） and lipoic acid group （0.026 8 g·kg

-1

·d

-1

）， and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4， 8， 12 weeks after intervention. At the 12

week， motor nerve conduction velocity （MNCV）， sensory nerve conduction velocity （SNCV）， nerve blood flow velocity， mechanical pain threshold， and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin （HE） staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， interleukin-1

（IL-1

）， and tumor necrosis factor-

（TNF-

） in sciatic nerve were determined by enzyme-related immunosorbent assay （ELISA）. The mRNA expressions of AMPK

， AMPK

， PGC-1

， and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction （Real-time PCR）.

Result

Compared with the normal group， fasting blood glucose in the model group was increased at each time point （

0.01）. The mechanical pain threshold was decreased （

0.05）， and the incubation time of the hot plate was extended （

0.01）. MNCV， SNCV， and nerve blood flow velocity decreased （

0.05）. The expression level of SOD was decreased （

0.01）. The expression levels of MDA， IL-1

， and TNF-

were increased （

0.01）. The mRNA expression levels of AMPK

， AMPK

， PGC-1

， and SIRT3 were decreased （

0.01）. The structure of sciatic nerve fibers in the model group was loose， and the arrangement was disordered. The demyelination change was obvious. Compared with the model group， the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks （

0.01）. The mechanical pain threshold increased （

0.05）. The incubation time of the hot plate was shortened （

0.01）. MNCV， SNCV， and Flux increased （

0.05）. The expression level of SOD was increased （

0.01）. The expression levels of MDA， IL-1

， and TNF-

were decreased （

0.01）. The mRNA expression levels of AMPK

， AMPK

， PGC-1

， and SIRT3 were increased （

0.01）. The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged， with only a few demyelinating changes. The high， medium， and low dose Tangbikang granule groups showed a significant dose-effect trend.

Conclusion

Tangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1

/SIRT3 signaling pathway partly to inhibit oxidative stress.

关键词

Keywords

references

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Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20231327

摘要

Abstract

关键词

Keywords

references