经皮神经电刺激对痛觉敏化诱发模型大鼠背根神经节IL-33/ST2信号通路的影响  

Effects of transcutaneous electrical nerve stimulation on IL-33/ST2 signaling pathway in the dorsal root ganglion of rats modeling hyperalgesia

作　　者：金莹 马黎倩 熊冰[1] 周杰[2] 林士明 崔清风[1] 李水泉 沈茜[1] Jin Ying;Ma Liqian;Xiong Bing;Zhou Jie;Lin Shiming;Cui Qingfeng;Li Shuiquan;Shen Qian(Department of Rehabilitation Medicine,The Second Afiliated Hospital of Zhejiang University School of Medicine,Hangzhou 310000,China;The Third Clinical Medical College and Rehabilitation Medical College of Zhejiang Traditional Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江大学医学院附属第二医院康复医学科,杭州310000 [2]浙江中医药大学第三临床医学院、康复医学院,杭州310053

出　　处：《中华物理医学与康复杂志》2024年第10期871-879,共9页Chinese Journal of Physical Medicine and Rehabilitation

基　　金：浙江省自然科学基金(LQ21H270008);浙江省医药卫生科技计划项目(2022492789);浙江省中医药科技计划(2024ZL577)。

摘　　要：目的探究经皮神经电刺激(TENS)对痛觉敏化诱发(HP)模型大鼠背根神经节(DRG)白细胞介素-33(IL-33)/受体生长刺激表达基因2蛋白(ST2)信号通路的影响。方法本研究分为2个实验进行。实验1,将30只SD大鼠按照随机数字表法分为空白组、假HP组、HP组、抗体组、抑制剂组,每组6只;除空白组和假HP组外,其余组大鼠在左后足足底皮下注射角叉菜胶(Car)和前列腺素E2(PGE2),建立HP模型;抗体组和抑制剂组大鼠,分别给予鞘内注射抗ST2抗体和肿瘤坏死因子α(TNF-α)特异性抑制剂;以Car注射为基准点(0 h),在4 h、24 h、48 h、72 h,以及7 d、7 d 1 h、7 d 4 h、7 d 24 h,对大鼠行机械痛阈检测;Car注射后7 d 24 h,采用免疫荧光技术和Western blot法检测各组大鼠IL-33、ST2和TNF-α的表达情况。实验2,将42只SD大鼠按照随机数字表法分为假HP组、HP组、TENSⅠ组、TENSⅡ组、TENSⅠ抑制剂组、TENSⅡ抑制剂组、假TENS组,每组6只;所有大鼠均建立HP模型,造模方法和假HP组处理方法同实验1;TENSⅠ组、TENSⅡ组、TENSⅠ抑制剂组、TENSⅡ抑制剂组均给予TENS干预,TENSⅠ抑制剂组和TENSⅡ抑制剂组大鼠均给予鞘内注射TNF-α特异性抑制剂;以Car注射为基准点(0 h),在4 h、24 h、48 h、72 h,以及7 d、7 d 1 h、7 d 4 h、7 d 24 h,对大鼠行机械痛阈检测;Car注射后7 d 24 h,采用Western blot法检测各组大鼠IL-33、ST2和TNF-α的蛋白表达水平。结果实验1,Car注射后4 h、24 h、48 h、72 h,与空白组和假HP组同时间点比较,HP组、抗体组、抑制剂组大鼠的机械痛阈显著降低(P<0.05);Car注射后7 d 1 h,假HP组、抗体组、抑制剂组大鼠的机械痛阈较HP组显著升高(P<0.05),IL-33、ST2和TNF-α表达较HP组显著降低(P<0.05)。实验2,Car注射后4 h、24 h、48 h、72 h,与假HP组比较,其余组大鼠的机械痛阈显著降低(P<0.05);Car注射后7 d 1 h,经TNES干预大鼠的机械痛阈较假TENS组显著升高(P<0.05);TENSⅡ组大鼠的Objective To explore the effect of transcutaneous electrical nerve stimulation(TENS)on interleukin-33(IL-33)/growth stimulation expressed gene 2(ST2)signaling pathway in the dorsal root ganglia(DRGs)of rats modeling hyperalgesia(HP).Methods This study consisted of two experiments.In the first,30 Sprague-Dawley(SD)rats were randomly divided into a blank group,a Sham-HP group,an HP group,an antibody group and an inhibitor group,each of 6.HP was induced in all except the rats of the blank and Sham-HP groups by injecting carrageenan(Car)and prostaglandin E2 subcutaneously at the bottom of the left hind feet.The antibody and inhibitor groups were then given intrathecal injections of anti-ST2 antibody and a tumor necrosis factorα(TNF-α)-specific inhibitor,respectively.In the second experiment,42 SD rats were randomly divided into a Sham-HP group,an HP group,a TENSⅠgroup,a TENS Ⅱ group,a TENS Ⅰ inhibitor group,a TENS Ⅱ inhibitor group,and a Sham-TENS group,each of 6.All of the groups had HP induced as in experiment one.All of the rats except those in the Sham-HP,HP and Sham-TENS groups were then given TENS,and the TENS Ⅰ and Ⅱ inhibitor groups were offered intrathecal injection of TNF-α-specific inhibitors.Mechanical pain thresholds(MPTs)were documented 4h,24h,48h,72h,6d,7d 4h,7d 1h,and 7d after the Car injections.Western blotting was used to measure the protein expressions of IL-33,ST2 and TNF-α6d after the Car injection in both experiments.Results In experiment one,the average MPTs of the HP,antibody and inhibitor groups had decreased significantly 4 hours after the Car injection compared with the blank and Sham-HP groups.However,7d 1h after the Car injection the value had increased significantly in the Sham-HP,antibody and inhibitor groups compared with the HP group,while the expressions of IL-33,ST2 and TNF-αhad decreased significantly.In experiment two,by 4 hours after the Car injection,the average MPT of all the other groups had decreased significantly compared with the Sham-HP group.Moreover,by 7

关 键 词：经皮神经电刺激 痛觉转化 背根神经节 白细胞介素-33 受体生长刺激表达基因2蛋白 肿瘤坏死因子α 

分 类 号：R338[医药卫生—人体生理学]