【摘要】 目的:慢性疼痛如炎性疼痛的基因治疗缺乏安全且高效的载体,本实验探讨了细胞穿透肽Tat-LK15介导si RNA干扰大鼠脊髓背角n NOS表达进而治疗慢性炎性疼痛的可行性。方法:参照前期实验,检测鞘内注射Tat-LK15/si RNA对完全弗氏佐剂(CFA)炎性痛模型大鼠脊髓背角(SCDH)n NOS蛋白表达的影响,并测定鞘内注射此复合物后炎性痛大鼠机械缩足反射阈值(MWT)及热缩足反射持续时间(TWD)的变化。结果:Tat-LK15/si RNA注射后3 d,炎性疼痛大鼠SCDH n NOS蛋白水平的表达下降51%(P<0.01),Tat-LK15/sc RNA注射后n NOS的表达无明显变化。Tat-LK15/si RNA鞘内注射后3、7、14及21d炎性痛大鼠的MWT显著增高,TWD显著缩短(P<0.01),Tat-LK15/sc RNA无此治疗作用。结论:TatLK15可有效运载si RNA抑制CFA所致慢性炎性痛大鼠n NOS的过度表达,从而对炎性疼痛大鼠具有治疗作用。更多还原

【Abstract】 Objective To investigate the potential application of a non-viral gene carrier,TAT-LK15,for delivering n NOSsi RNAin vivo and to study whether TAT-LK15 / si RNA can be a new treatment method for chronic inflammatory pain.Method TAT-LK15 was complexed with n NOSsi RNA or scrambled control si RNA.The expression of n NOS was determined in SCDH of chronic inflammatory pain rats by western-blot assay.Pain control efficacy was evaluated by mechanical withdrawal threshold(MWT) and thermal withdrawal duration(TWD) assays.Results n NOS protein expression was efficiently inhibited by intrathecal injection of TAT-LK15 /si RNA complexes,with the reduction of n NOS protein by 52%.Moreover,injection of TAT-LK15 / si RNA complexes significantly could decrease MWT,but increase TWD in rats with chronic inflammatory pain.Conclusions TAT-LK15 can efficiently deliver n NOSsi RNAin vivo and n NOSsi RNA can relieve chronic inflammatory pain in rats.更多还原