利多卡因对三叉神经痛大鼠p2x7-p38-IL-Iβ通路的影响  

Effects of lidocaine on p2x7-p38-IL-Iβ pathway in rats with trigeminal neuralgia

作　　者：吴美能 邵敬宝 Wu Meineng;Shao Jingbao(Department of Pharmacy,Jiaxing First Hospital,Affiliated Hospital of Jiaxing University,Jiaxing,Zhejiang314001,China;Department of Pharmacy,Zhejiang University of Traditional Chinese Medicine,Hangzhou,Zhejiang 310053,China)

机构地区：[1]嘉兴市第一医院嘉兴学院附属医院药学部,浙江嘉兴314001 [2]浙江中医药大学药学系,浙江杭州310053

出　　处：《中国药物与临床》2024年第22期1467-1471,F0003,共6页Chinese Remedies & Clinics

摘　　要：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。Objective To investigate the effects of lidocaine on p2x7-p38-IL-1βpathway 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-1βin 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-1βin 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-1βin 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

关 键 词：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 

分 类 号：R965[医药卫生—药理学]