本文選題：神經(jīng)鈣蛋白　切入點(diǎn)：奧沙利鉑　出處：《廣東醫(yī)學(xué)》2017年08期

【摘要】：目的探討神經(jīng)鈣蛋白(CaN)在奧沙利鉑引起的神經(jīng)病理性疼痛中的作用。方法取鼠齡為6周的SPF級(jí)SD雄性大鼠,體重約200~250 g,前期將大鼠隨機(jī)分為兩組(n=5):生理鹽水組和CIPN模型組。CIPN模型組大鼠采用腹腔注射6 mg/kg奧沙利鉑誘發(fā)其發(fā)生外周神經(jīng)性病變(CIPN),于模型制備前2 d及制備后的1、2、3、4、5、7、14 d,采用von frey細(xì)絲測定各組大鼠左后足機(jī)械痛縮足閾值(PWT),選擇疼痛最高點(diǎn)作為實(shí)驗(yàn)點(diǎn)。正式實(shí)驗(yàn)將大鼠隨機(jī)分為3組(n=12):對照組(處理前)、CIPN模型7 d組、CIPN模型14 d組。于模型制備后7和14 d,痛閾測定結(jié)束后,取L_(4～5)段脊髓背角(DH)及背根神經(jīng)節(jié)(DRG),采用qPCR和Western blot方法分別檢測DH和DRG中CaN mRNA及其蛋白表達(dá)水平,采用免疫熒光雙標(biāo)記法檢測DRG中星形膠質(zhì)細(xì)胞標(biāo)志物膠質(zhì)纖維酸性蛋白(GFAP)、小膠質(zhì)細(xì)胞標(biāo)志物植物凝集素(IB4)、CaN的表達(dá)。結(jié)果 CIPN模型組大鼠術(shù)后第2、3、4、5、7、14天的PWT均較生理鹽水組的同時(shí)間點(diǎn)的PWT顯著下降(P0.05),且PWT在單次注射6 mg/kg奧沙利鉑后的第7和14天到達(dá)最低點(diǎn)。在DH中,第7、14天CaN mRNA表達(dá)相較于對照組有所下調(diào);在DRG中,第7、14天CaN mRNA的表達(dá)水平與對照組相比無明顯變化,蛋白表達(dá)水平與mRNA表達(dá)水平保持一致。在DH和DRG中,對照組中GFAP、CaN及IB4、CaN大量共表達(dá),而在CIPN模型7、14 d組中共表達(dá)明顯減少,且胞體形態(tài)發(fā)生變化。結(jié)論奧沙利鉑可能主要積累在DRG和DH中,對周圍的神經(jīng)造成損傷,誘導(dǎo)CaN表達(dá)下調(diào),降低PWT值,導(dǎo)致痛覺的發(fā)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.
【作者單位】： 中山大學(xué)腫瘤防治中心華南腫瘤學(xué)國家重點(diǎn)實(shí)驗(yàn)室腫瘤醫(yī)學(xué)協(xié)同創(chuàng)新中心麻醉科;
【基金】：國家自然科學(xué)基金資助項(xiàng)目(編號(hào):81401036)
【分類號(hào)】：R965

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