Effect of <italic style="font-style: italic">Tangbikang</italic> （糖痹康） on Oxidative Stress， Mitochondrial Energy Metabolism and AMPK/SIRT3 Pathway in Sciatic Nerve of Diabetes Model Rat

YU Ruiqin; ZHANG Yaqi; ZHANG Chengfei; ZHANG Qiue; MU Xiaohong; BAI Huizhong; ZUO Xinwei; LIU Gang; LIU tonghua; QIN Lingling

doi:10.13288/j.11-2166/r.2023.11.012

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Effect of Tangbikang （糖痹康） on Oxidative Stress， Mitochondrial Energy Metabolism and AMPK/SIRT3 Pathway in Sciatic Nerve of Diabetes Model Rat

更新时间：2023-06-05

- Effect of Tangbikang （糖痹康） on Oxidative Stress， Mitochondrial Energy Metabolism and AMPK/SIRT3 Pathway in Sciatic Nerve of Diabetes Model Rat
- Journal of Traditional Chinese Medicine Vol. 64, Issue 11, Pages: 1140-1148(2023)
- 作者机构：
  
  1.北京中医药大学东直门医院，北京市东城区海运仓5号，100700
  2.北京中医药大学生命科学学院
  3.北京中医药大学中医学院
  4.北京中医药大学教育部中医养生学重点实验室
  5.北京中医药大学科技处/教育部高等学校学科创新引智基地
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.11.012
  CLC：
- Received：08 September 2022，
  
  Revised：2023-02-13，
  
  Published：02 June 2023
- 稿件说明：
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于睿钦,张亚奇,张程斐等.糖痹康对糖尿病模型大鼠坐骨神经氧化应激、线粒体能量代谢及AMPK/SIRT3通路的影响[J].中医杂志,2023,64(11):1140-1148.

YU Ruiqin,ZHANG Yaqi,ZHANG Chengfei,et al.Effect of Tangbikang （糖痹康） on Oxidative Stress， Mitochondrial Energy Metabolism and AMPK/SIRT3 Pathway in Sciatic Nerve of Diabetes Model Rat[J].Journal of Traditional Chinese Medicine,2023,64(11):1140-1148.
于睿钦,张亚奇,张程斐等.糖痹康对糖尿病模型大鼠坐骨神经氧化应激、线粒体能量代谢及AMPK/SIRT3通路的影响[J].中医杂志,2023,64(11):1140-1148. DOI： 10.13288/j.11-2166/r.2023.11.012.

YU Ruiqin,ZHANG Yaqi,ZHANG Chengfei,et al.Effect of Tangbikang （糖痹康） on Oxidative Stress， Mitochondrial Energy Metabolism and AMPK/SIRT3 Pathway in Sciatic Nerve of Diabetes Model Rat[J].Journal of Traditional Chinese Medicine,2023,64(11):1140-1148. DOI： 10.13288/j.11-2166/r.2023.11.012.

摘要

目的

探讨糖痹康对糖尿病坐骨神经病变的影响及可能作用机制。

方法

60只雄性SD大鼠随机分为正常组、模型组、硫辛酸组和糖痹康高、中、低剂量组，每组10只。除正常组外，其余各组大鼠采用高脂高糖饲料饲养+链脲佐菌素腹腔注射建立糖尿病大鼠模型。造模成功后硫辛酸组大鼠予硫辛酸注射液0.0268 g/（kg·d）进行腹腔注射，糖痹康高、中、低剂量组分别予糖痹康颗粒剂2.5、1.25、0.625 g/（kg·d）灌胃，正常组和模型组予生理盐水10 ml/kg灌胃，均连续干预12周。各组分别于给药前和给药4、8、12周检测血糖、体质量；给药12周后，检测大鼠热痛阈与坐骨神经运动神经传导速度（MNCV），取大鼠坐骨神经检测氧化应激指标［超氧化物歧化酶（SOD）、丙二醛（MDA）］、炎症因子［白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）］、线粒体能量代谢指标［烟酰胺腺嘌呤二核苷酸（NAD

）、还原型辅酶Ⅰ（NADH

）、三磷酸腺苷（ATP）］水平；HE染色检测大鼠坐骨神经切片组织形态，电镜观察大鼠坐骨神经超微结构；检测大鼠坐骨神经腺苷酸活化蛋白激酶（AMPK）/去乙酰化酶3（SIRT3）通路相关蛋白［磷酸化腺苷酸活化蛋白激酶（p-AMPK）、AMPK、过氧化物增殖激活受体协同激活因子1α（PGC-1α）、SIRT3、神经元型一氧化氮合酶（nNOS）、线粒体转录因子A（TFAM）］表达。

结果

给药4、8、12周时糖痹康高、中剂量组血糖显著低于模型组（

＜0.05或

＜0.01）。各药物干预组在各个时间点与模型组体质量差异均无统计学意义（

＞0.05）。给药12周后，与正常组比较，模型组大鼠热痛阈、MDA、IL-1β、TNF-α、NADH

均升高，MNCV、SOD、NAD

、NAD

/NADH

、ATP及PGC-1α、SIRT3、TFAM、nNOS蛋白表达均降低（

＜0.05或

＜0.01）。与模型组比较，糖痹康各剂量组与硫辛酸组热痛阈、MDA、IL-1β、TNF-α降低，MNCV、SOD升高，糖痹康高剂量组在降低热痛阈、IL-1β、TNF-α，升高MNCV、SOD方面优于糖痹康中、低剂量组（

＜0.05或

＜0.01）。与模型组比较，各药物干预组NAD

、NAD

/NADH

、ATP升高，硫辛酸组和糖痹康高、中剂量组PGC-1α、SIRT3、TFAM、nNOS蛋白表达升高（

＜0.05或

＜0.01），糖痹康高剂量组在升高NAD

/NADH

、ATP方面优于硫辛酸组，糖痹康高剂量组在升高PGC-1α、TFAM方面优于糖痹康中、低剂量组（

＜0.05）。光镜及电镜结果显示，模型组大鼠的坐骨神经纤维结构损伤，线粒体结构紊乱，髓鞘板层结构严重破坏，髓鞘出现裂隙与空泡，脱髓鞘病变明显，而各药物干预组坐骨神经纤维病理损伤有不同程度的改善，且以硫辛酸组和糖痹康高剂量组改善明显。

结论

糖痹康可能通过调控坐骨神经AMPK/SIRT3通路，抑制线粒体氧化应激，减轻炎症反应，提高线粒体能量代谢，从而对糖尿病坐骨神经病变起到修复与神经保护作用。

Abstract

Objective

To observe the effect and possible mechanism of

Tangbikang

（糖痹康） on diabetic sciatic neuropathy in diabetes.

Methods

Sixty male SD rats were randomly divided into normal group， model group， lipoic acid group and

Tangbikang

high-， medium- and low-dose groups， with 10 rats in each group. Except for the normal group， rats were fed with high-fat and high-sugar diet plus intraperitoneal injection of streptozotocin to establish diabetes model. After successful modeling， corresponding interventions including 0.0268 g/（kg·d） of lipoic acid injection intraperitoneally injected， 2.5， 1.25， and 0.625 g/d of

Tanbikang

granules by gavage， and 10 ml/kg of normal saline by gavage were respectively taken in lipoic acid group，

Tangbikang

high-， medium- and low-dose groups， normal group and model group. All interventions continued for 12 weeks. Before medication and after 4， 8 and 12 weeks of treatment， the blood glucose and body weight of each group were measured. After 12 weeks， the thermal pain threshold and sciatic nerve motor nerve conduction velocity （MNCV） were measured. The sciatic nerves of rats were taken， and the oxidative stress indicators including superoxide dismutase （SOD） and Malondialdehyde （MDA）， the inflammatory factors including interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， and mitochondrial energy metabolism indicators including nicotinamide adenine dinucleotide （NAD

）， reduced coenzyme （NADH

） and adenosine triphosphate （ATP） were detected. Hematoxylin eosin （HE） staining was used to detect the histological morphology of the sciatic nerve sections， and the ultrastructure of the sciatic nerve was observed by electron microscopy. The expression of adenylate-activated protein kinase （AMPK）/ sirtuin 3 （SIRT3） pathway-related proteins in sciatic nerve were detected including phosphorylated AMP-activated protein kinase （p-AMPK）， AMPK， peroxisome proliferator-activated receptor coactivator 1α （PGC-1α）， SIRT3， neuronal nitric oxide synthase （nNOS） and mitochondrial transcription factor A （TFAM）.

Results

After 4， 8 and 12 weeks of treatment， the blood glucose of

Tangbikang

high- and medium-groups were significantly lower than that of the model group （

＜0.05 or

＜0.01）. There was no signi-ficant difference in body weight between all the intervention groups and the model group at each timepoint （

＞0.05）. After 12 weeks of treatment， the model group had increased thermal pain threshold， MDA， IL-1β， TNF-α and NADH

， as well as decreased MNCV， SOD， NAD

， NAD

/NADH

， ATP levels and protein expressions of PGC-1α， SIRT3， TFAM and nNOS as compared to the normal group （

＜0.05 or

＜0.01）. Compared to those in the model group， the thermal pain threshold， MDA， IL-1β and TNF-α levels decreased， while MNCA and SOD levels increased in all

Tangbikang

groups and the lipoic acid group， and

Tangbikang

high-dose group was superior to the medium- and low-dose groups （

＜0.05 or

＜0.01） in the above-mentioned indicators but MDA. Compared to those in the model group， the NAD

， NAD

/NADH

and

ATP in all intervention groups increased； the protein expressions of PGC-1α， SIRT3， TFAM and nNOS in lipoic acid group and

Tangbikang

high- and medium-dose groups increased （

＜0.05 or

＜0.01）； the

Tangbikang

high-dose group was superior to the lipoic acid group in increasing NAD

/NADH

and ATP， and was superior to the medium- and low-dose groups （

＜0.05） in increasing PGC-1α and TFAM.Light and electron microscopy showed that in the model group， the structure of the sciatic nerve fibers was damaged， and the mitochondrial structure was disordered， with severly destroyed myelin sheath lamellar structure， cracks and vacuoles appearing in the myelin sheath， and obvious demyelinating lesions； the pathogenic damage of sciatic nerve fibers in all intervention groups was improved to varying degrees， and the lipoic acid group and

Tangbikang

high-dose group improved more significantly.

Conclusion

Tangbikang

may play repairing and neuro-protecting role in diabetes peripheral neuropathy by regulating the sciatic nerve AMPK/SIRT3 pathway， inhibiting mitochondrial oxidative stress， reducing inflammatory response， and improving mitochondrial energy metabolism.

关键词

Keywords

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Effect of Tangbikang （糖痹康） on Oxidative Stress， Mitochondrial Energy Metabolism and AMPK/SIRT3 Pathway in Sciatic Nerve of Diabetes Model Rat

DOI：10.13288/j.11-2166/r.2023.11.012

摘要

Abstract

关键词

Keywords

references