miR-99b-5p靶向FGFR3对紫杉醇诱导慢性神经病理性疼痛形成的影响  

miR-99b-5p targeting FGFR3 inhibits the paclitaxel-induced chronic neuralgia

作　　者：韩聪 徐力 曾文玉 辜文艳 刘庆 HAN Cong;XU Li;ZENG Wenyu;GU Wenyan;LIU Qing(Department of Pain Medicine,the Affiliated Hospital of Southwest Medi-cal University,Luzhou 646000,China;Department of Operating Theatre,the Affiliated Hospital of Southwest Medi-cal University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属中医医院疼痛科 [2]西南医科大学附属中医医院手术室,泸州646000

出　　处：《中国疼痛医学杂志》2021年第10期737-743,共7页Chinese Journal of Pain Medicine

基　　金：西南医科大学-西南医科大学附属中医医院联合项目(2020XYLH-055)。

摘　　要：目的:探讨miR-99b-5p对紫杉醇诱导的大鼠慢性神经病理性疼痛的影响。方法:成年SD雄性大鼠,按照简单随机化的方法分为空白组(blank)、紫杉醇模型组(modle)、agomiR-99b-5p治疗组和agomiR-NC对照组,每组8只。采用隔日腹腔注射紫杉醇(2 mg/kg,共4次)的方法制备紫杉醇诱导的慢性神经病理性疼痛大鼠模型。检测大鼠机械缩足反射阈值(mechanical withdrawal threshold,MWT)和热缩足反射潜伏期(thermal withdrawal latency,TWL);RT-qPCR检测miR-99b-5p的表达,判断agomiR-99b-5p的激活作用和背根神经节中炎症因子TNF-α、IL-6和IL-1β含量的变化;Western Blot检测背根神经节成纤维细胞生长因子受体3(fibroblast growth factor receptor 3,FGFR3)的变化;双荧光素酶报告基因实验检测miR-99b-5p对FGFR3的靶向作用。结果:agomiR-99b-5p能显著增加大鼠背根神经节miR-99b-5p的含量,降低紫杉醇诱导的慢性神经病理性疼痛大鼠的MWT和TWL,同时也能显著下调背根神经节的炎症因子水平。荧光素酶结果表明相对于NC模拟物(mimic)组,miR-99b-5p mimic能够抑制FGFR3的表达。结论:miR-99b-5p能够影响FGFR3的表达,进而抑制背根神经节炎症因子的含量,达到降低紫杉醇诱导大鼠慢性神经病理性疼痛的目的。Objective:To investigate the effects of miR-99b-5p on paclitaxel-induced chronic neuralgia in rats.Methods:Following the simple randomization method,male SD rats were divided into the blank group,paclitaxel model group,agomiR-99b-5p group and agomiR-NC group.Paclitaxel-induced chronic neuralgia rats were prepared by intraperitoneal injection of paclitaxel(2 mg/kg,four times in total)every other day.Mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured in these rats.RT-qPCR was used to detect the expression of miR-99b-5p,TNF-α,IL-6,and IL-1βin dorsal root ganglia of rats.Western Blot was used to detect the expression of fibroblast growth factor receptor 3(FGFR3),and luciferase assay was used to detect the targeting effect of miR-99b-5p on FGFR3.Results:AgomiR-99b-5p significantly increased the concentration of miR-99b-5p in the dorsal root ganglia,reduced the MWT and TWL in paclitaxel-induced chronic neuralgia rats,and significantly down-regulated the levels of inflammatory factors in dorsal root ganglia.The luciferase experiment indicated that miR-99b-5p mimic inhibited FGFR3 expression compared with the NC mimic group.Conclusion:MiR-99b-5p can target and inhibit the expression of FGFR3,and further inhibit the concentrations of inflammatory factors in dorsal root ganglia,thus alleviating paclitaxel-induced chronic neuralgia in rats.

关 键 词：紫杉醇 慢性神经痛 miR-99b-5p 成纤维细胞生长因子受体3 

分 类 号：R741[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]