摘要
目的比较不同剂量下沙利度胺影响肿瘤坏死因子受体(TNFR)表达水平对大鼠慢性坐骨神经缩窄(CCI)镇痛效果及其潜在临床价值。方法 50只大鼠随机分为S组、C组、L组、M组及H组,S组为假手术组,其余4组建立CCI模型,术后分别用20、50、100 mg/kg沙利度胺处理为L组、M组、H组,余为C组,于术后第1、2、3及4周测量机械性痛阈与热痛阈并运用重复测量方差分析各组差异;蛋白质印迹法(Western印迹)及实时荧光定量聚合酶链反应(PCR)(Q-PCR)分析4组TNFR基因表达产物相对含量,比较各组TNFR mRNA和蛋白表达差异;运用Pearson相关性分析显示沙利度胺浓度与TNFR mRNA相对表达间的关系。结果与S组相比,4组术后机械性痛阈、热痛阈均显著下降(P<0.05);与C组比较,L组、M组与H组术后机械性痛阈、热痛阈呈上升趋势(P<0.05),H组显著高于M组(F机械性痛阈=6.432,P机械性痛阈=0.000;F热痛阈=5.445,P热痛阈=0.000),而M组显著高于L组(F机械性痛阈=8.045,P机械性痛阈=0.000;F热痛阈=5.673,P热痛阈=0.000);相对于C组,L组、M组、H组术后第4周TNFR1 mRNA及蛋白相对含量显著下降(P<0.05),其中H组下降最为明显,M组次之;Pearson相关性分析显示:沙利度胺浓度增加与TNFR1表达升高呈明显负相关(r=-0.497,P=0.036)。结论沙利度胺可能通过影响TNFR表达对CCI大鼠产生镇痛效应,其镇痛效应随剂量增加而加强,有望作为神经病理性疼痛的辅助镇痛药物之一。
Objective To explore the association between TNF receptor levels affected by thalidomide at different doses and analgesic effect on CCI rat model. Methods Fifty rats were randomly divided into S,C,L,M and H groups. Then, S group was defined as sham operation group and the CCI model was established in the rest groups. L, M and H groups were treated by 20, 50 and 100 mg/kg thalidomide following CCI, respectively.The mechanical pain threshold and thermal pain threshold of the five groups were measured at the first, second, third and the 4 th week after operation, and the differences among the five groups were analyzed by repeated measurement of variance. Western blot and real-time quantitative PCR were applied to test the contents of INFR mRNA and protein of the four CCI model groups.Results Compared with those of S group, the mechanical pain thresholds and thermal pain thresholds of four CCI model groups were dropped significantly(P<0.05). The mechanical pain thresholds and thermal pain thresholds of L, M and H groups were risen at different times after operation and those in group H were higher than those in group M(FMPT=6.432,PMPT=0.000;FTWL=5.445,PTWL=0.000), while those in M group were higher than those of L group(FMPT=8.045,PMPT=0.000;FTWL=5.673,PTWL=0.000). Compared with those of C group, the expression levels of TNFR1 mRNA and protein in L, M and H groups were decreased significantly(P<0.05) and those of M group were the lowest. The concentration of TNFR1 and the level of thalidomide had significant negative correlation(r=-0.497,P=0.036). Conclusions Thalidomide might has an analgesic effect on chronic sciatic nerve of rats by affecting the level of TNFR and the analgesic effect is enhanced with increasing dose, which is expected as one of auxiliary analgesic drugs for neuropathic pain.
作者
苏晓英
陈素明
周飞仁
王清秀
SU Xiao-Ying;CHEN Su-Ming;ZHOU Fei-Ren(Department of Anesthesiology, Sichuan Province Mianyang Third People′s Hospital,Mianyang 621000, Sichuan, China)
出处
《中国老年学杂志》
CAS
北大核心
2019年第11期2720-2723,共4页
Chinese Journal of Gerontology
基金
上海浦东新区科技发展基金(PKJ2011-y17)
