三叉神经痛导致与 CD95/CD95L 通路上调相关的大鼠神经退行性变。

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway.

机构信息

Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, P.R. China.

Laboratory of Anesthesiology, Affiliated Hospital of Southwest Medical University, Luzhou, P.R. China.

出版信息

Mol Pain. 2020 Jan-Dec;16:1744806920908092. doi: 10.1177/1744806920908092.

DOI:10.1177/1744806920908092

PMID:32013712

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7054737/

Abstract

OBJECTIVES

To explore the effects of trigeminal neuralgia on neurodegeneration in rats and the underlining mechanism.

METHODS

Sixty adult male Sprague Dawley rats were divided randomly into Chronic Constriction Injury of the Rat’s Infraorbital Nerve (ION-CCI) group and sham group ( = 30). Right suborbital nerve was ligated in ION-CCI group to establish a trigeminal neuralgia model. In sham group, suborbital nerve was exposed without ligation. Pain thresholds were measured before surgery and 1, 7, 15, and 30 days after surgery ( = 10). Morris water maze tests ( = 10) were conducted at 1, 15, and 30 days after surgery to evaluate the changes in learning and memory ability of rats. At 5, 19, and 34 days after surgery, serum S100β protein concentration and hippocampal Aβ1-42 protein expression were detected by enzyme-linked immunosorbent assay; total tau protein expression was detected by Western blotting; changes of neurons in hippocampus were observed by Nissl staining; and the expression of p-tau, cluster of differentiation (CD)95, CD95L, and cleaved caspase-3 proteins was detected by immunofluorescence and Western blotting.

RESULTS

Hyperalgesia occurred in ION-CCI group, and mechanical pain threshold decreased significantly ( < 0.05). On the 15th and 30th days after surgery, ION-CCI group showed lower learning and memory ability than sham group ( < 0.05). Serum S100β protein concentration, hippocampal A β1-42, and p-tau protein expression increased in the ION-CCI group 19 and 34 days after surgery (< 0.05), hippocampal CD95 expression increased in the ION-CCI group after surgery ( < 0.05), hippocampal CD95L expression increased at 19 and 34 days after surgery ( < 0.05), and cleaved caspase-3 expression increased at 5 and 19 days after surgery ( < 0.05). Nissl bodies in ION-CCI group decreased significantly at 15 days after surgery. The expression of cleaved caspase-3 protein in ION-CCI group was positively correlated with the expression of CD95 and CD95L ( < 0.05).

CONCLUSIONS

Trigeminal neuralgia may lead to neuronal inflammation and neuronal apoptosis associated with upregulation of CD95/CD95L expression, thus causing neurodegeneration.

摘要

目的

探讨三叉神经痛对大鼠神经退行性变的影响及其潜在机制。

方法

将 60 只成年雄性 Sprague Dawley 大鼠随机分为慢性眶下神经结扎（ION-CCI）组和假手术组（每组 n=30）。ION-CCI 组结扎右侧眶下神经建立三叉神经痛模型，假手术组仅暴露眶下神经而不结扎。术前及术后 1、7、15 和 30 天（每组 n=10）测定疼痛阈值。术后 1、15 和 30 天（每组 n=10）进行 Morris 水迷宫测试，以评估大鼠学习记忆能力的变化。术后 5、19 和 34 天（每组 n=10）通过酶联免疫吸附试验检测血清 S100β 蛋白浓度和海马 Aβ1-42 蛋白表达，通过 Western blot 检测总 tau 蛋白表达，通过尼氏染色观察海马神经元变化，通过免疫荧光和 Western blot 检测磷酸化 tau（p-tau）、分化抗原（CD）95、CD95L 和半胱氨酸天冬氨酸蛋白酶-3（cleaved caspase-3）蛋白的表达。

结果

ION-CCI 组出现痛觉过敏，机械性痛觉阈值显著降低（<0.05）。术后 15 和 30 天，ION-CCI 组学习记忆能力较假手术组降低（<0.05）。术后 19 和 34 天，ION-CCI 组血清 S100β 蛋白浓度、海马 Aβ1-42 和 p-tau 蛋白表达增加（<0.05），术后 ION-CCI 组海马 CD95 表达增加（<0.05），术后 19 和 34 天海马 CD95L 表达增加（<0.05），术后 5 和 19 天 cleaved caspase-3 表达增加（<0.05）。术后 15 天 ION-CCI 组尼氏体明显减少。ION-CCI 组 cleaved caspase-3 蛋白表达与 CD95 和 CD95L 表达呈正相关（<0.05）。