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利多卡因对三叉神经痛大鼠p2x7-p38-IL-Iβ通路的影响

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目的 探讨利多卡因对三叉神经痛p2x7-p38-IL-Iβ通路的影响。方法 雄性SD大鼠随机数字表法分为3组:假手术组、手术组(ION-CCI组)、利多卡因组(ION-CCI+L组)。假手术组:钝性分离右侧眶下神经但不结扎+腹腔注射等体积0。9%氯化钠注射液;ION-CCI组:分离右侧眶下神经并结扎+腹腔注射等体积0。9%氯化钠注射液;ION-CCI+L组:分离右侧眶下神经并结扎+腹腔注射利多卡因10 mg·kg-1·d-1。术前、术后1 d、3 d、5 d、7 d、9 d、11 d、14 d行大鼠机械痛阈测定。术后14 d腹腔注射戊巴比妥钠(60 mg/kg)麻醉并灌注取脑组织、三叉神经节。采用酶联免疫吸附试验(ELISA)检测大鼠丘脑、三叉神经节白细胞介素(IL)-1β的表达水平,蛋白质免疫印迹法检测大鼠丘脑P2X7、p38、p-p38、IL-1β的表达水平,免疫荧光检测大鼠丘脑p-p38的表达水平。结果 ION-CCI+L组大鼠痛阈较假手术组降低(P<0。01),较ION-CCI组增高(P<0。01);ELISA结果显示,ION-CCI+L组大鼠丘脑、三叉神经节IL-1β浓度较ION-CCI组降低(P<0。05),较假手术组增高(P<0。05);蛋白质免疫印迹法结果显示ION-CCI+L组大鼠丘脑p2x7、p-p38的表达水平较ION-CCI组降低(P<0。01)、较假手术组增高(P<0。01),ION-CCI+L组大鼠丘脑IL-1β的表达水平较ION-CCI组降低(P<0。05)、较假手术组增高(P<0。01)、各组大鼠丘脑p38的表达水平差异无统计学意义(P>0。05);免疫荧光结果显示ION-CCI+L组大鼠丘脑区p-p38的荧光强度较ION-CCI组降低(P<0。05)、较假手术组增高(P<0。05)。结论 利多卡因可缓解大鼠三叉神经痛,降低三叉神经痛大鼠丘脑和三叉神经节IL-1β的表达水平、降低丘脑p2x7、p-p38的表达水平,提示利多卡因可能通过抑制P2X7-p38-IL-1β通路抑制中枢神经系统炎症反应从而缓解三叉神经痛。
Effects of lidocaine on p2x7-p38-IL-Iβ pathway in rats with trigeminal neuralgia
Objective To investigate the effects of lidocaine on p2x7-p38-IL-1β pathway in trigeminal neuralgia. Methods All male SD rats were divided into three groups by random number table method:sham surgery group (Sham group),surgery group (ION-CCI group),and lidocaine group (ION-CCI+L group). Sham group:blunt separation of the right infraorbital nerve without ligation+intraperitoneal injection of equal volume 0.9%sodium chloride injection;ION-CCI group:blunt separation of the right infraorbital nerve and ligation+intraperitoneal injection of equal volume 0.9%sodium chloride injection;ION-CCI+L group:blunt separation of the right infraorbital nerve and ligation+intraperitoneal injection of lidocaine 10 mg·kg-1·d-1. Mechanical pain threshold measurements were performed on rats before surgery and on postoperative days 1,3,5,7,9,11,and 14 days after surgery,intraperitoneal injection of pentobarbital sodium (60 mg/kg) was administered for anesthesia,and brain tissue and trigeminal ganglia were collected by perfusion. The expression levels of IL-1β in the thalamus and trigeminal ganglia of rats were detected using enzyme-linked immunosorbent assay (ELISA). The expression levels of p2x7,p38,p-p38,and IL-1β in the thalamus of rats were detected using protein immunoblotting. The expression level of p-p38 in rat thalamus was detected by immunofluorescence. Results The pain threshold of ION-CCI+L group rats was lower than that of Sham group (P<0.01),but higher than that of ION-CCI group (P<0.01);The ELISA results showed that the concentration of IL-1β in the thalamus and trigeminal ganglia of rats in the ION-CCI+L group was lower than that in the ION-CCI group (P<0.01),but higher than that in the Sham group (P<0.01). The results of protein immunoblotting showed that the expression levels of p2x7 and p-p38 in the thalamus of rats in the ION-CCI+L group were lower than those in the ION-CCI group (P<0.01),but higher than those in the Sham group (P<0.01);The expression level of IL-1β in the thalamus of ION-CCI+L group rats was lower than that of ION-CCI group (P<0.01),but higher than that of Sham group (P<0.01). There was no statistically significant difference in the expression level of p38 in the thalamus of rats in all the groups ( P>0.05). The immunofluorescence results showed that the fluorescence intensity of p-p38 in the thalamic region of ION-CCI+L group rats was lower than that of ION-CCI group (P>0.05),but higher than that of Sham group (P>0.05). Conclusion Lidocaine can alleviate trigeminal neuralgia,reduce the expression level of IL-1β in thalamus and trigeminal ganglion of trigeminal neuralgia rats,and decrease the expression level of p2X7 and p-p38 in thalamus of trigeminal neuralgia rats,suggesting that lidocaine may inhibit the central nervous system inflammatory by inhibiting the p2x7-p38-IL-1β pathway,thereby alleviating trigeminal neuralgia

Receptors,purinergic p2x7MAP kinase signaling systemp38 mitogen-activated protein kinasesInterleukin-1 betaLidocaineTrigeminal neuralgia

吴美能、邵敬宝

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嘉兴市第一医院嘉兴学院附属医院药学部,浙江嘉兴 314001

浙江中医药大学药学系,浙江杭州 310053

受体,嘌呤能P2X7 MAP激酶信号系统 p38丝裂原活化蛋白激酶类 白细胞介素-1β 利多卡因 三叉神经痛

2024

中国药物与临床
中国医院协会

中国药物与临床

影响因子:0.846
ISSN:1671-2560
年,卷(期):2024.24(22)