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1. 北京朝阳急诊抢救中心麻醉科
2. 首都医科大学附属北京朝阳医院麻醉科
纸质出版日期:2021,
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梁自飞, 吴安石, 沈文振, 等. 基于NLRP3炎症小体信号通路探讨盐酸小檗碱对三叉神经痛大鼠的影响[J]. 中国医院用药评价与分析, 2021,21(6):658-662.
LIANG Zifei, WU Anshi, SHEN Wenzhen, et al. Effects of Berberine Hydrochloride on Trigeminal Neuralgia in Rats Based on NLRP3 Inflammatory Signaling Pathway[J]. 2021,21(6):658-662.
梁自飞, 吴安石, 沈文振, 等. 基于NLRP3炎症小体信号通路探讨盐酸小檗碱对三叉神经痛大鼠的影响[J]. 中国医院用药评价与分析, 2021,21(6):658-662. DOI: 10.14009/j.issn.1672-2124.2021.06.005.
LIANG Zifei, WU Anshi, SHEN Wenzhen, et al. Effects of Berberine Hydrochloride on Trigeminal Neuralgia in Rats Based on NLRP3 Inflammatory Signaling Pathway[J]. 2021,21(6):658-662. DOI: 10.14009/j.issn.1672-2124.2021.06.005.
目的:探讨盐酸小檗碱对三叉神经痛(trigeminal neuralgia
TN)大鼠模型中NOD样受体蛋白3(NLRP3)炎症小体信号通路的影响以及对TN模型大鼠的保护作用。方法:采用眶下神经缩窄术制备TN大鼠模型
将造模成功的大鼠随机分为模型组和盐酸小檗碱低、中及高剂量组(25 mg/kg、50 mg/kg及100 mg/kg)
每组15只。另取15只大鼠(仅分离眶下神经
不结扎)作为假手术组
假手术组和模型组大鼠予以等量0.9%氯化钠溶液灌胃
其他各组大鼠灌胃予以相应剂量的盐酸小檗碱
灌胃体积10 ml/kg
1日1次
共14 d。采用电子测痛仪测定各组大鼠在不同时间的神经颜面部支配区机械痛阈值;采用酶联免疫吸附试验检测大鼠术侧三叉神经节组织中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平;采用实时荧光定量聚合酶链式反应检测各组大鼠术侧三叉神经节组织中降钙素基因相关肽(CGRP)、NLRP3、凋亡相关斑点样蛋白(ASC)及胱天蛋白酶1(caspase-1)的mRNA表达水平;采用蛋白质免疫印迹法检测大鼠术侧三叉神经节组织中CGRP、NLRP3、ASC及caspase-1的蛋白表达水平。结果:建模前3、1 d
各组大鼠机械痛阈值比较
差异均无统计学意义(P> 0.05);建模后1、3 d
与假手术组比较
模型组大鼠机械痛阈值明显降低
差异有统计学意义(P <0.05)
而模型组和盐酸小檗碱低、中及高剂量组大鼠机械痛阈值两两比较的差异均无统计学意义(P> 0.05)。建模后5~14 d
与假手术组比较
模型组大鼠机械痛阈值明显降低
差异有统计学意义(P <0.05);与模型组比较
盐酸小檗碱低、中及高剂量组大鼠机械痛阈值依次升高
呈剂量依赖性
差异均有统计学意义(P <0.05)。术后第15日
与假手术组比较
模型组大鼠三叉神经节组织中IL-1β、TNF-α含量
CGRP、NLRP3、ASC及caspase-1的mRNA、蛋白表达水平均明显升高
差异均有统计学意义(P <0.05);与模型组比较
盐酸小檗碱低、中及高剂量组大鼠三叉神经节组织中IL-1β、TNF-α含量
CGRP、NLRP3、ASC及caspase-1的mRNA、蛋白表达水平依次降低
呈剂量依赖性
差异均有统计学意义(P <0.05)。结论:盐酸小檗碱可能通过下调NLRP3炎症小体信号通路减少炎症因子释放
降低术侧三叉神经节组织中CGRP表达水平
提高神经面部感觉区域的机械痛阈值
从而减轻TN对大鼠的损伤作用。
OBJECTIVE: To probe into the effects of berberine hydrochloride on the inflammatory signaling pathway of NOD-like receptor protein 3( NLRP3) in rats with trigeminal neuralgia( TN) and its protective effect on TN rats. METHODS: TN rat model was made by chronic constriction injury of infraorbital nerve model( ION-CCI)method. The successfully modeled rats were randomly divided into the model group
low-dose group
medium-dose group and high-dose group of berberine hydrochloride( 25 mg/kg
50 mg/kg
100 mg/kg)
with 15 rats in each group. Another 15 rats( only the infraorbital nerve was isolated
without ligation) were taken as the sham operation group. The sham operation group and the model group were given the same amount of normal saline by gavage. The other groups received the corresponding dose of berberine hydrochloride by gavage with the volume of 10 ml/kg
once a day for 14 d. The mechanical pain threshold of facial innervation at different time points were measured by electronic pain tester. The levels of interleukin-1β( IL-1β)
tumor necrosis factor-α( TNF-α) in trigeminal ganglia of rats were detected by enzyme-linked immunosorbent assay( ELISA). The expression level of calcitonin gene-related peptide( CGRP)
NLRP3
apoptosis-related speckle-like protein( ASC) and caspase-1 mRNA in the trigeminal ganglion tissues of rats were detect by real-time fluorescent quantitative polymerase chain reaction( qRT-PCR). And the expression level of CGRP
NLRP3
ASC and caspase-1 protein in trigeminal ganglia were detected by Western Blot.RESULTS: Before modeling of 3 d and 1 d
there was no statistically significant difference in mechanical pain threshold among four groups( P > 0. 05). After modeling of 3 d and 1 d
compared with the sham operation group
the mechanical pain threshold in the model group decreased
with statistically significant difference( P < 0. 05)
and there was no statistically significant difference between the model group and low-dose group
medium-dose group and highdose group of berberine hydrochloride( P > 0. 05). After modeling of 5 to 14 d
compared with the sham operation group
the mechanical pain threshold in the model group decreased
with statistically significant difference( P <0. 05); compared with the model group
the mechanical pain threshold of low-dose group
medium-dose group and high-dose group of berberine hydrochloride increased in turn with dose-dependent( P < 0. 05). On the 15 th d after surgery
compared with the sham operation group
the level of IL-1β
TNF-α and the expression level of mRNA and protein in CGRP
NLRP3
ASC and caspase-1 in trigeminal ganglion tissue of the rats in the model group increased
with statistically significant difference( P < 0. 05); compared with the model group
the level of IL-1β
TNF-α and the mRNA and protein expression level of CGRP
NLRP3
ASC and caspase-1 in the trigeminal ganglion tissue of the rats in the low-dose group
medium-dose group and high-dose group of berberine hydrochloride decreased in turn with dose-dependent( P < 0. 05). CONCLUSIONS: Berberine hydrochloride may reduce the release of inflammatory factors by down-regulating the signal pathway of NLRP3 inflammatory corpuscle
decrease the expression level of CGRP in trigeminal ganglion tissues
and increase the mechanical pain sensitivity threshold of the neurofacial sensory area
so as to reduce the injury of TN on rats.
盐酸小檗碱三叉神经痛NOD样受体蛋白3炎症小体信号通路降钙素基因相关肽
Berberine hydrochlorideTrigeminal neuralgiaNOD-like receptor protein 3 inflammatory corpuscle signaling pathwayCalcitonin gene-related peptide
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