神经钙蛋白在奥沙利铂引起的神经病理性疼痛中的作用

发布时间：2018-03-30 12:40

本文选题：神经钙蛋白　切入点：奥沙利铂　出处：《广东医学》2017年08期

【摘要】：目的探讨神经钙蛋白(CaN)在奥沙利铂引起的神经病理性疼痛中的作用。方法取鼠龄为6周的SPF级SD雄性大鼠,体重约200~250 g,前期将大鼠随机分为两组(n=5):生理盐水组和CIPN模型组。CIPN模型组大鼠采用腹腔注射6 mg/kg奥沙利铂诱发其发生外周神经性病变(CIPN),于模型制备前2 d及制备后的1、2、3、4、5、7、14 d,采用von frey细丝测定各组大鼠左后足机械痛缩足阈值(PWT),选择疼痛最高点作为实验点。正式实验将大鼠随机分为3组(n=12):对照组(处理前)、CIPN模型7 d组、CIPN模型14 d组。于模型制备后7和14 d,痛阈测定结束后,取L_(4～5)段脊髓背角(DH)及背根神经节(DRG),采用qPCR和Western blot方法分别检测DH和DRG中CaN mRNA及其蛋白表达水平,采用免疫荧光双标记法检测DRG中星形胶质细胞标志物胶质纤维酸性蛋白(GFAP)、小胶质细胞标志物植物凝集素(IB4)、CaN的表达。结果 CIPN模型组大鼠术后第2、3、4、5、7、14天的PWT均较生理盐水组的同时间点的PWT显著下降(P0.05),且PWT在单次注射6 mg/kg奥沙利铂后的第7和14天到达最低点。在DH中,第7、14天CaN mRNA表达相较于对照组有所下调;在DRG中,第7、14天CaN mRNA的表达水平与对照组相比无明显变化,蛋白表达水平与mRNA表达水平保持一致。在DH和DRG中,对照组中GFAP、CaN及IB4、CaN大量共表达,而在CIPN模型7、14 d组中共表达明显减少,且胞体形态发生变化。结论奥沙利铂可能主要积累在DRG和DH中,对周围的神经造成损伤,诱导CaN表达下调,降低PWT值,导致痛觉的发生及感受。
[Abstract]:Objective to investigate the role of calcitonin in neuropathic pain induced by oxaliplatin. The rats were randomly divided into two groups: normal saline group and CIPN model group. CIPN model rats were induced to develop peripheral neuropathy by intraperitoneal injection of 6 mg/kg oxaliplatin, 2 days before and 2 days after the preparation of the model. The von frey filament was used to measure the threshold of mechanical pain of left hind foot in each group for 14 days. The highest point of pain was selected as the experimental point. The rats were randomly divided into 3 groups: control group (7 days before treatment). Group d: at 7 and 14 days after the model was made, the pain threshold was measured. The expression of CaN mRNA and its protein in DH and DRG were detected by qPCR and Western blot. The expression of glial fibrillary acidic protein (glial fibrillary acidic protein) and microglial marker plant agglutinin (IB4) in DRG was detected by immunofluorescence double labeling method. Results the PWT of the CIPN model group was higher than that of the control group on the 2nd day after operation. The PWT of saline group decreased significantly at the same time point, and PWT reached its lowest point at 7 and 14 days after a single injection of oxaliplatin for 6 mg/kg. The expression of CaN mRNA was down-regulated on day 7 and 14, and the expression of CaN mRNA on day 714 in DRG was not significantly different from that in control group, and the protein expression level was consistent with that of mRNA. In DH and DRG, the expression of CaN mRNA was similar to that of control group. In the control group, GFAP can and IB4 can co-expressed in large quantities, but in the CIPN model 714 d group, the expression decreased significantly and the somatic morphology changed. Conclusion oxaliplatin may accumulate mainly in DRG and DH, causing damage to peripheral nerves and inducing down-regulation of CaN expression. Reduce the PWT value, leading to the occurrence and feeling of pain.
【作者单位】：中山大学肿瘤防治中心华南肿瘤学国家重点实验室肿瘤医学协同创新中心麻醉科;
【基金】：国家自然科学基金资助项目(编号:81401036)
【分类号】：R965

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