miR-99b-5p对紫杉醇致大鼠神经病理性疼痛的缓解作用及对神经细胞焦亡和凋亡的影响*

doi:10.12047/j.cjap.6289.2022.082

中国应用生理学杂志 ›› 2022, Vol. 38 ›› Issue (5): 438-442.doi: 10.12047/j.cjap.6289.2022.082

miR-99b-5p对紫杉醇致大鼠神经病理性疼痛的缓解作用及对神经细胞焦亡和凋亡的影响^*

曾文玉¹, 辜文艳², 徐力¹, 张英¹, 韩聪^1△

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

收稿日期:2022-03-07 修回日期:2022-08-09 出版日期:2022-09-28 发布日期:2023-04-23
通讯作者: ^△Tel: 15196090960; E-mail: 408950003@qq.com
基金资助:
^*西南医科大学附属中医医院科研项目自然科学基金(2020XYLH-055)

miR-99b-5p inhibits the activation of NLRP3 inflammasome to alleviate the neurotoxicity induced by paclitaxel chemotherapy

ZENG Wen-yu¹, GU Wen-yan², XYU Li¹, ZHANG Ying¹, HAN Cong^1△

1. Department of Pain Medicine, the Affiliated T.C.M Hospital of Southwest Medical University;
2. Department of Operating Theatre, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, China

Received:2022-03-07 Revised:2022-08-09 Online:2022-09-28 Published:2023-04-23

摘要/Abstract

摘要： 目的: 研究miR-99b-5p(非编码RNA)通过抑制NLRP3炎性小体活化缓解紫杉醇化疗后病理性神经疼痛的干预作用,以及对神经细胞焦亡和凋亡的影响。方法: SD大鼠随机分为空白组(Blank)、模型组(Model)、agomiR-99b-5p治疗组和agomiR-NC对照组,每组6只。空白组接受生理盐水治疗作为对照,模型组通过紫杉醇诱导建立疼痛模型,agomiR-99b-5p组和agomiR-NC组为在模型组的基础上注射agomiR-99b-5p和agomiR-NC进行干预。RT-qPCR检测空白组、模型组、agomiR-99b-5p治疗组和agomiR-NC组大鼠背根神经节中miR-99b-5p的表达差异;vonFrey纤维丝检测空白组、模型组与治疗组机械缩足阈值(MWT);TUNEL法测定背根神经节细胞凋亡情况;试剂盒检测大鼠背根神经节中ROS、MDA和SOD;免疫荧光染色检测炎症小体NLRP3、Caspase-1和IL-1β蛋白的表达。结果: 与空白组比较,模型组miR-99b-5p含量较低;与模型组比较,agomiR-99b-5p治疗组可以显著增加大鼠背根神经节miR-99b-5p的水平(P＜0.05),增加大鼠机械缩足阈值(MWT)(P＜0.05),抑制背角细胞的凋亡,大鼠背根神经节ROS和MDA水平降低(P＜0.05),而SOD水平增加(P＜0.05)。免疫荧光显示,NLRP3、Caspase-1和IL-1β的表达水平可被miR-99b-5p抑制。结论: 在体内miR-99b-5p可以通过抑制NLRP3活化和改善机体氧化应激以缓解大鼠经紫杉醇化疗后的神经病理性疼痛及神经细胞焦亡和凋亡。

关键词: 背根神经节, miR-99b-5p, 氧化应激, NLRP3

Abstract: Objective: To study the effects of miR-99b-5p (non-coding RNA) in alleviating pathological neuropathic pain after paclitaxel chemotherapy by inhibiting NLRP3 inflammatory vesicle activation and the effects on neuronal cells pyrosis and apoptosis. Methods: SD rats were randomly divided into blank group, model group, agomiR-99b-5P treatment group, and agomiR-NC group, 6 rats in each group. The blank group received saline treatment as a control, the model group established a pain model induced by paclitaxel, and the rats in agomiR-99b-5p treatment group and agomiR-NC group were treated with agomiR-99b-5p and agomiR-NC injections, respectively. The expressions of miR-99b-5p in the blank group, model group, and treatment group were detected by RT-qPCR. The mechanical foot retraction threshold (MWT) of the blank group, model group, and treatment group were detected. TUNEL was used to detect the apoptosis of spinal dorsal horn cells. The levels of ROS, MDA, and SOD were detected by ELISA kits. The protein expressions of NLRP3, caspase-1, and IL-1β were detected by immunofluorescence staining. Results: Compared with the model group, the expression level of miR-99b-5p and the MWT were increased significantly in agomiR-99b-5p treatment group (P＜0.05), the apoptosis of dorsal horn cells was inhibited (P＜0.05), the level of antioxidant stress was increased in rats, the levels of ROS and MDA were decreased (P＜0.05), while the level of SOD was increased (P＜0.05). Immunofluorescence showed that the expressions of NLRP3, caspase-1, and IL-1β were inhibited by miR-99b-5p. Conclusion: miR-99b-5p can alleviate the apoptosis and pyroptosis of neurons after paclitaxel chemotherapy by inhibiting the activation of NLRP3 and improving oxidative stress in vivo.

Key words: dorsal root ganglion, miR-99b-5p, oxidative stress, NLRP3

中图分类号:

R741

曾文玉, 辜文艳, 徐力, 张英, 韩聪. miR-99b-5p对紫杉醇致大鼠神经病理性疼痛的缓解作用及对神经细胞焦亡和凋亡的影响^*[J]. 中国应用生理学杂志, 2022, 38(5): 438-442.

ZENG Wen-yu, GU Wen-yan, XYU Li, ZHANG Ying, HAN Cong. miR-99b-5p inhibits the activation of NLRP3 inflammasome to alleviate the neurotoxicity induced by paclitaxel chemotherapy[J]. CJAP, 2022, 38(5): 438-442.

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miR-99b-5p对紫杉醇致大鼠神经病理性疼痛的缓解作用及对神经细胞焦亡和凋亡的影响^*

miR-99b-5p inhibits the activation of NLRP3 inflammasome to alleviate the neurotoxicity induced by paclitaxel chemotherapy

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