针刺研究2024，Vol.49Issue(4)：349-357,9.DOI:10.13702/j.1000-0607.20221318
基于Sirt1/PGC-1α/TFAM通路探讨电针治疗2型糖尿病周围神经病变的机制
Electroacupuncture improves peripheral neuropathy by up-regulating Sirt1/PGC-1α/TFAM pathway in type 2 diabetes rats with peripheral neuropathy
摘要
Abstract
Objective To observe the effect of electroacupuncture(EA)on activation of silent information regulator 1(Sirt1)/peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α)/mitochondrial transcription factor A(TFAM)pathway in type 2 diabetes(T2DM)rats with peripheral neuropathy(DPN),so as to explore its possible mechanisms underlying improvement of DPN.Methods Thirty male SD rats were randomly divided into blank control group(n=8)and DPN model group(n=22)which were further divided into model group(n=8)and EA group(n= 8)after successful modeling.The model of T2DM was established by high-fat diet and low-dose intraperitoneal injection of streptozocin(35 mg/kg).For rats of the EA group(anesthetized with isoflurane),EA stimulation(2 Hz/15 Hz,2 mA)was applied to"Tianshu"(ST25)for 20 min,once daily,6 times a week for 6 weeks.The blood glucose level,body weight,area under curve(AUC)of glucose tolerance test,and hind-paw mechanical pain threshold and thermal pain threshold were observed.The intra-epidermal nerve fiber density(IENFD)of the hind-foot pad was observed by immunofluorescence staining.The motor nerve conduction velocity(MNCV)of the sciatic nerve was measured by using electrophysiological method.H.E.staining was used to observe the histopathological changes of the sciatic nerve after modeling.Transmission electron microscopy(TEM)was used to observe the ultrastructural changes of the sciatic nerve.The protein expressions of energy-related Sirt1,PGC-1α and TFAM in the sciatic nerve was detected by Western blot.Results Compared with the blank control group,the model group had a higher blood glucose contents and AUC(P<0.001),a slower MNCV(P<0.01),and a decrease in the body weight and in the mechanical and thermal pain thresholds(P<0.001)and IENFD(P<0.001),and in the expression levels of Sirt1,PGC-1α and TFAM(P<0.05,P<0.01).In contrast to the model group,the EA group had a decrease in the blood glucose contents and AUC(P<0.05,P<0.01),and an increase in mechanical and thermal pain thresholds,MNCV,IENFD,and expression levels of Sirt1,PGC-1α and TFAM proteins(P<0.01,P<0.05).In addition,results of histopathological and ultrastructural changes of the sciatic nerve showed more fragmented and disordered distribution of axons on the transverse section,and extensive separation of myelin and axons,uneven myelin thickness,axonal degeneration and irregular shape in the model group,whereas in the EA group,the axons on the transverse section were relatively more dense and more complete,the myelin sheath of the sciatic nerve was relatively uniform,and the axonal shape was relatively regular with relatively milder lesions.Conclusion EA up-regulates the expressions of Sirt1,PGC-1α,TFAM in T2DM rats with DPN,which may be associated with its functions in improving and repairing the injured peripheral nerves in rats with DPN.关键词
糖尿病周围神经病变/电针/Sirt1/PGC-1α/TFAM通路Key words
Diabetic peripheral neuropathy/Electroacupuncture/Sirt1/PGC-1α/TFAM pathway引用本文复制引用
袁重茜,王璇,余芝,连晓阳,徐斌..基于Sirt1/PGC-1α/TFAM通路探讨电针治疗2型糖尿病周围神经病变的机制[J].针刺研究,2024,49(4):349-357,9.基金项目
国家自然科学基金项目(No.81873238、82074532、81574071、81673883) （No.81873238、82074532、81574071、81673883）
江苏省研究生科研创新计划项目(No.KYCX22_1963) （No.KYCX22_1963）
