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1.贵州中医药大学第一附属医院麻醉科,贵阳 550001
2.贵州中医药大学第一附属医院泌尿外科,贵阳 550001
3.贵州中医药大学第一临床医学院中医内科,贵阳 550025
4.贵州中医药大学第一附属医院皮肤科,贵阳 550001
陈太长,Email:491938581@qq.com,研究方向:小胶质细胞自噬、带状疱疹后神经痛、TRPV1调控。
唐松江,Email:38594728@qq.com。
收稿:2024-03-05,
修回:2024-09-06,
录用:2025-01-02,
纸质出版:2025-08-28
移动端阅览
陈太长,蹇忠禄,丁维,等.TRPV1介导小胶质细胞自噬在带状疱疹后神经疼痛中的作用和分子机制[J].重庆医科大学学报,2025,50(8):1058-1063.
Chen Taichang,Jian Zhonglu,Ding Wei,et al.Role of TRPV1-mediated microglia autophagy in postherpetic neuralgia and molecular mechanism[J].Journal of Chongqing Medical University,2025,50(8):1058-1063.
陈太长,蹇忠禄,丁维,等.TRPV1介导小胶质细胞自噬在带状疱疹后神经疼痛中的作用和分子机制[J].重庆医科大学学报,2025,50(8):1058-1063. DOI: 10.13406/j.cnki.cyxb.003747.
Chen Taichang,Jian Zhonglu,Ding Wei,et al.Role of TRPV1-mediated microglia autophagy in postherpetic neuralgia and molecular mechanism[J].Journal of Chongqing Medical University,2025,50(8):1058-1063. DOI: 10.13406/j.cnki.cyxb.003747.
目的
2
探究瞬时感受器电位香草酸亚型1(transient receptor potential vanilloid 1,TRPV1)介导小胶质细胞自噬在带状疱疹后神经疼痛中的作用机制。
方法
2
40只小鼠随机分为正常组(Con)、带状疱疹后神经痛组(postherpetic neuralgia,PHN)、阴性对照组(PHN-sh-NC)、TRPV1干扰组(PHN-sh-TRPV1),每组10只。检测小鼠机械缩足阈值(mechanical withdrawal threshold,MWT)和热痛阈潜伏期(thermal withdrawal latency,TWL);ELISA检测血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1 beta,IL-1β)、白细胞介素6(interleukin-6,IL-6)、脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)水平;透射电镜检测脊髓组织中自噬体形成;免疫荧光检测脊髓组织中微管相关蛋白轻链3(microtubule-associated protein 1 light chain 3,LC3)、离子钙结合适配器分子1(ionized calcium-binding adapter molecule 1,Iba-1)表达;Western blot检测脊髓组织中Beclin-1、自噬微管相关蛋白轻链3β(microtubule-associated protein 1 light chain 3 beta,LC3B)、类似核孔糖蛋白p62(similar to nuclear pore glycoprotein p62,p62)蛋白表达。
结果
2
和Con组相比,PHN组和PHN-sh-NC组小鼠、血清BNDF(
t
=10.49,
P
<
0.001)水平及脊髓组织中p62(
P
=0.004)蛋白表达明显降低,小鼠血清中TNF-α(
t
=26.27,
P
<
0.001)、IL-1β(
t
=17.0,
P
<
0.001)、IL-6(
t
=25.48,
P
<
0.001)水平及脊髓组织中Iba-1(
P
=0.002)、LC3(
P
<
0.001)表达和Beclin-1(
P
=0.001)、LC3B(
P
<
0.001)蛋白表达明显升高;和PHN组相比,PHN-sh-TRPV1组小鼠MWT、血清BNDF(
t
=5.174,
P
<
0.001)水平及脊髓组织中p62(
P
<
0.001)蛋白表达明显升高;TWL、血清中TNF-α(
t
=20.57,
P
<
0.001)、IL-1β(
t
=8.260,
P
<
0.001)和IL-6(
t
=19.81,
P
<
0.001)水平及脊髓组织中Iba-1(
P<
0.001)、LC3(
P=
0.001)表达和LC3B(
P
<
0.001)、Beclin-1(
P
<
0.001)蛋白表达明显降低。
结论
2
PHN小鼠脊髓小胶质细胞自噬激活,抑制TRPV1表达可通过抑制小胶质细胞自噬缓解带状疱疹后神经痛小鼠的疼痛。
Objective
2
To investigate the mechanism of transient receptor potential vanilloid subfamily 1(TRPV1)-mediated microglia autophagy in postherpetic neuralgia.
Methods
2
Forty mice were randomly divided into control group,postherpetic neuralgia(PHN) group,PHN-sh-NC group,and PHN-sh-TRPV1 group,with 10 mice in each group. We tested the mice’s mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL);measured serum levels of tumor necrosis factor-alpha(TNF-α),interleukin (IL)-1β,IL-6,and brain-derived neurotrophic factor(BDNF) by enzyme-linked immunosorbent assay; assessed the formation of autophagosomes in the spinal cord tissues by transmission electron microscopy; measured the expression of microtubule-associated protein 1 light chain 3(LC3) and ionized calcium binding adaptor molecule 1(Iba-1) in the spinal cord tissues by immunofluorescence assay;and determined the protein expression of Beclin-1,microtubule-associated protein 1 light chain 3B(LC3B),and p62 in the spinal cord tissues by Western blot.
Results
2
Compared with the control group,the PHN group and PHN-sh-NC group had significant decreases in MWT,serum BNDF level(
t
=10.49,
P
<
0.001),and p62(
P
=0.004) protein expression in the spinal cord tissues and significant increases in TWL,serum TNF-α(
t
=26.27,
P
<
0.001),IL-1β(
t
=17.0,
P
<
0.001),and IL-6 levels(
t
=25.48,
P
<
0.001),and the expression of Iba-1(
P
=0.002),LC3(
P
<
0.001),LC3B(
P
=0.001),and Beclin-1 proteins(
P
=0.001)in the spinal cord tissues. Compared with the PHN group,the PHN-sh-TRPV1 group had a significantly higher MWT,a significantly higher serum BNDF level(
t
=5.174,
P
<
0.001,a significantly higher p62 protein expression level (
P
<
0.001)in the spinal cord tissues,a significantly lower TWL,significantly lower serum TNF-α(
t
=20.57,
P
<
0.001),IL-1β(
t
=8.260,
P
<
0.001),and IL-6 levels(
t
=19.81,
P
<
0.001),and significantly lower expression levels of Iba-1(
P
<
0.001),LC3(
P
<
0.001),LC3B(
P
=0.001),and Beclin-1(
P
<
0.001) in the spinal cord tissues.
Conclusion
2
Microglia autophagy is activated in the spinal cord of PHN mice,and suppressing the expression of TRPV1 can inhibit microglia autophagy to relieve pain in PHN mice.
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