WSLP运载siRNA抑制炎性疼痛大鼠脊髓背角 NMDA 受体1基因表达的可行性  

Water soluble lipopolymer can be efficient siRNA delivery targeting NMDA receptor 1 in rats with chronic inflammatory pain

作　　者：马国亮[1] 杨雪[2] 董文芳[2] 彭捷[2] 陆建华[2] 党健[3] 

机构地区：[1]解放军第四二一医院,广州市510318 [2]广州军区广州总医院麻醉科,广州市510010 [3]广州军区广州总医院心功能室,广州市510010

出　　处：《实用医学杂志》2013年第18期2971-2973,共3页The Journal of Practical Medicine

基　　金：国家自然科学青年基金项目(编号:81100817);广州市科技计划项目(编号:10C36091669);广东省自然科学基金面上项目(编号:S2012010009271)

摘　　要：目的:探讨低分子量聚乙烯亚胺(PEI)和胆固醇组成的水溶性脂聚体(WSLP)运载siRNA抑制炎性疼痛大鼠脊髓背角(SCDH)N-甲基-D-天冬氨酸受体功能亚基(NR1)基因表达的可行性及其对炎性疼痛大鼠机械性痛阈值的影响。方法:将WSLP直接与靶向NR1的siRNA连接形成WSLP/siRNA复合物,乱序siRNA作为对照(WSLP/scRNA);然后分别检测鞘内注射WSLP/siRNA对炎性痛模型大鼠SCDH NR1转录水平及蛋白水平表达的影响,并且测定鞘内注射此复合物后炎性痛大鼠50%机械性痛阈值的变化。结果:WSLP/siRNA注射后3 d,炎性疼痛大鼠SCDH NR1转录水平表达下降41%(P<0.01),蛋白水平的表达相应下降58%(P<0.01),WSLP/scRNA及PEI/siRNA注射后NR1转录水平及蛋白水平的表达无明显变化。WSLP/siRNA鞘内注射后3、7、14及21 d炎性痛大鼠的50%机械性痛阈值显著增高(P<0.01),WSLP/scRNA及PEI/siRNA均无此作用。结论:WSLP可有效运载siRNA抑制慢性炎性痛大鼠NR1的过度表达,从而治疗炎性疼痛大鼠痛觉过敏。Objective To examine the potential application of a non-viral gene carrier, water soluble lipopolymer （WSLP） for delivering siRNA targeting NRI in chronic inflammatory pain treatment. Method WSLP was complexed with siRNA （designed to inhibit NR1 expression） or scrambled siRNA. Changes of NR1 mRNA and protein expression were detected using Q-PCR and western-blot in SCDH of chronic inflammatory pain rats following intratbecal injection of WSLP/siRNA. Pain control efficacy was evaluated by changes of 50% mechanical withdrawal threshold （MWT） in these rats. Results 3 days after injection, the changes of mRNA and protein level was reduced by 41% and 58% respectively compared to chronic inflammatory pain rats without treatment, while complexes injection of WSLP with scrambled siRNA or PEI with siRNA did not show this inhibitory effect. Moreover, injection of WSLP/siRNA complexes significantly inhibited the decrease of 50% MWT in chronic inflammatory pain rats. Conclusions WSLP can efficiently deliver siRNA for inhibiting NR1 overexpression in rats with chronic inflammatory pain and thus have treatment roles in these rats.

关 键 词：炎性疼痛 水溶性脂聚体 NMDA受体1 小干涉RNA 

分 类 号：R363[医药卫生—病理学]