背根神经节STAT3/CCL2信号通路在泰素诱导慢性疼痛中的作用  

Involvement of STAT3/CCL2 Pathway in the Paclitaxel-induced Chronic Pain in Dorsal Root Ganglion

作　　者：廖维勇[1] 王勇[1] 黄文君[1] 唐名杰 LIAO Wei-yong;WANG yong;HUANG Wen-jun;TANG Ming-jie(Department of Physiology,Guilin Medical University;Department of Oncology,Guilin Women and Children′s Hospital,Guilin 541500,China)

机构地区：[1]桂林医学院生理教研室 [2]桂林市妇女儿童医院肿瘤科,广西桂林541500

出　　处：《中山大学学报（医学科学版）》2020年第3期415-423,共9页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金地区科学基金(81560378)。

摘　　要：【目的】研究转录因子STAT3通过上调背根神经节趋化因子CCL2的表达介导泰素诱导慢性疼痛的机制。【方法】66只大鼠随机分成6组,包括:溶剂对照组(V)、泰素组(T)、鞘内注射CCL2中和性抗体+泰素组(A+T)、鞘内注射S3I-201+泰素组(S+T)、泰素+溶剂组(T+R)、鞘内注射C188-9+泰素组(C+T)。连续5 d腹腔注射化疗药泰素,建立慢性疼痛模型。采用蛋白印迹法、RT-qPCR方法和免疫组织化学方法,确定STAT3、CCL2在背根神经节表达的变化和细胞类型。鞘内注射CCL2中和性抗体,观察对泰素诱导慢性疼痛的影响。最后,鞘内注射STAT3抑制剂S3I-201,观察对泰素诱导慢性疼痛及背根神经节CCL2表达的影响。【结果】腹腔注射泰素显著诱导机械性慢性疼痛,同时上调背根神经节神经元CCL2和STAT3的表达。预先鞘内注射CCL2中和性抗体显著缓解慢性疼痛。此外,鞘内注射STAT3抑制剂S3I-201和C188-9均显著缓解泰素诱导机械性慢性疼痛和CCL2表达上调。【结论】转录因子STAT3通过上调趋化因子CCL2表达介导化疗药泰素诱导的慢性疼痛。【Objective】To examined the mechanism underlying the activation of CCL2/STAT3 signal pathway in the paclitaxel-induced chronic pain.【Methods】A total of sixty-six rats were randomly divided into 5 groups,including:vehicle group(V),Paclitaxel group(T),intrathecal injection of CCL2 neutralizing antibody Paclitaxel group(A+T),intrathecal injection of S3I-201+Paclitaxel group(S+T),Paclitaxel+Vehicle group(T+R),and intrathecal injection of C188-9+Paclitaxel group(C+T).Following paclitaxel treatment for a consecutive 5 day,the expression of CCL2 and STAT3 in DRG were observed by using Western blotting,RT-qPCR and Immunohistochemistry.Furthermore,following the intrathecal injection of neutralizing CCL2 antibody,the paw withdrawal threshold was observed.At last,by the application of STAT3 inhibitors S3I-201 or C188-9(i.t.),we explored the change of paw withdrawal threshold and CCL2 level.【Results】Paclitaxel treatment(i.p.)significantly induced the chronic pain(P<0.01),and increased the expression of CCL2(P<0.01)and STAT3(P<0.01)in DRG.Pre-intrathecal injection of neutralizing CCL2 antibody markedly attenuated the chronic pain induced by paclitaxel treatment(P<0.01).Moreover,Pre-application of S3I-201(P<0.01)or C188-9(P<0.01)attenuated the chronic pain and decreased the CCL2(P<0.01)upregulation in DRG induced by paclitaxel treatment.【Conclusion】CCL2 upregulation mediated by STAT3 pathway contributes to the paclitax?el-induced chronic pain.

关 键 词：慢性疼痛 背根神经节 泰素 STAT3 CCL2 

分 类 号：R338.1[医药卫生—人体生理学]