硫辛酸通过 NF-κB 下调 TRPV1 受体，减轻糖尿病大鼠的神经病理性疼痛。

Alpha-lipoic acid downregulates TRPV1 receptor via NF-κB and attenuates neuropathic pain in rats with diabetes.

机构信息

Department of Endocrinology, The Second Affiliated Hospital, Soochow University, Suzhou, China.

Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China.

出版信息

CNS Neurosci Ther. 2020 Jul;26(7):762-772. doi: 10.1111/cns.13303. Epub 2020 Mar 16.

AIMS

Painful diabetic neuropathy (PDN) is a refractory complication of diabetes. The study aimed to investigate the role of α-lipoic acid (ALA) on the regulation of transient receptor potential vanilloid-1 (TRPV1) in dorsal root ganglion (DRG) neurons of rats with diabetes.

METHODS

Whole-cell patch-clamp recordings were employed to measure neuronal excitability in DiI-labeled DRG neurons of control and streptozotocin (STZ)-induced diabetic rats. Western blotting and immunofluorescence assays were used to determine the expression and location of NF-κBp65 and TRPV1.

RESULTS

STZ-induced hindpaw pain hypersensitivity and neuronal excitability in L4-6 DRG neurons were attenuated by intraperitoneal injection with ALA once a day lasted for one week. TRPV1 expression was enhanced in L4-6 DRGs of diabetic rats compared with age-matched control rats, which was also suppressed by ALA treatment. In addition, TRPV1 and p65 colocated in the same DRG neurons. The expression of p65 was upregulated in L4-6 DRGs of diabetic rats. Inhibition of p65 signaling using recombinant lentiviral vectors designated as LV-NF-κBp65 siRNA remarkably suppressed TRPV1 expression. Finally, p65 expression was downregulated by ALA treatment.

CONCLUSION

Our findings demonstrated that ALA may alleviate neuropathic pain in diabetes by regulating TRPV1 expression via affecting NF-κB.

目的

痛性糖尿病周围神经病变（PDN）是糖尿病的一种难治性并发症。本研究旨在探讨α-硫辛酸（ALA）在调节糖尿病大鼠背根神经节（DRG）神经元瞬时受体电位香草酸 1（TRPV1）中的作用。

方法

采用全细胞膜片钳记录技术测量对照组和链脲佐菌素（STZ）诱导的糖尿病大鼠 DiI 标记的 DRG 神经元的神经元兴奋性。采用 Western blot 和免疫荧光检测法测定 NF-κBp65 和 TRPV1 的表达和定位。

结果

腹腔注射 ALA 每天一次，持续一周，可减轻 STZ 诱导的大鼠后爪痛觉过敏和 L4-6 DRG 神经元的兴奋性。与同龄对照组大鼠相比，糖尿病大鼠 L4-6 DRG 中 TRPV1 的表达增强，ALA 处理也抑制了 TRPV1 的表达。此外，TRPV1 和 p65 共定位于相同的 DRG 神经元。糖尿病大鼠 L4-6 DRG 中 p65 的表达上调。用重组慢病毒载体抑制 p65 信号通路，即 LV-NF-κBp65 siRNA，可显著抑制 TRPV1 的表达。最后，ALA 处理可下调 p65 的表达。