【摘要】：目的探討大鼠鞘內(nèi)注射細(xì)胞穿透肽Tat-LK15介導(dǎo)NR2B siRNA治療大鼠慢性炎性疼痛的可行性。方法健康雄性SD大鼠72只,6周齡,體質(zhì)量180~200 g,采用隨機(jī)數(shù)字表法分為4組(n=18):空白對(duì)照組(C組)、慢性炎性痛模型組(CFA組)、Tat-LK15/NR2B siRNA組(si Tat-LK15組)和Tat-LK15/陰性對(duì)照siRNA組(nc Tat-LK15組)。除C組不給予任何處理外,其余大鼠右后趾皮下注射完全弗氏佐劑(CFA)制作慢性炎性痛模型。CFA組、si Tat-LK15組及nc Tat-LK15組于模型制備后第1、3、5天分別鞘內(nèi)注射生理鹽水、Tat-LK15/NR2B siRNA及Tat-LK15/陰性對(duì)照siRNA 10μL。每組取12只大鼠于造模前1 d及鞘內(nèi)注射后3、7、14、21 d時(shí)測(cè)定機(jī)械縮足反應(yīng)閾(PWMT)和熱縮足反應(yīng)潛伏期(PWTL)。每組取6只大鼠于鞘內(nèi)注射后7 d處死后取脊髓,檢測(cè)鞘內(nèi)注射對(duì)大鼠脊髓NR2B蛋白表達(dá)的影響。結(jié)果鞘內(nèi)注射后7 d,si Tat-LK15組大鼠脊髓NR2B蛋白表達(dá)下調(diào)。鞘內(nèi)注射后3、7、14及21 d,si Tat-LK15組PWMT與PWTL與CFA組相比明顯升高,差異有統(tǒng)計(jì)學(xué)意義(P0.01),而nc Tat-LK15組PWMT與PWTL較CFA組相比差異無統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論鞘內(nèi)注射Tat-LK15/NR2B siRNA可有效減輕CFA所致大鼠慢性炎性疼痛。
[Abstract]:Objective to investigate the feasibility of intrathecal injection of cellular penetrating peptide (Tat-LK15) -mediated NR2B siRNA in the treatment of chronic inflammatory pain in rats. Methods 72 healthy male SD rats, aged 6 weeks and weighing 180 ~ 200g, were randomly divided into 4 groups (n = 18): blank control group (C group) and chronic inflammatory pain model group (CFA group). Tat-LK15/NR2B siRNA group (si Tat-LK15 group) and Tat-LK15/ negative control group siRNA group (nc Tat-LK15 group). The chronic inflammatory pain model was induced by subcutaneous injection of complete Freund's adjuvant (CFA) into the right hind toe of the other rats except for group C. CFA group, si Tat-LK15 group and nc Tat-LK15 group were treated with chronic inflammatory pain on the 1st day after the model was made. Intrathecal injection of normal saline, siRNA 10 渭 L in Tat-LK15/NR2B siRNA and Tat-LK15/ negative control group for 5 days. Mechanical foot contraction threshold (PWMT) and thermal foot contraction latency (PWTL).) of 12 rats in each group were measured 1 day before model making and at 21 days after intrathecal injection. Six rats in each group were killed 7 days after intrathecal injection and the effects of intrathecal injection on the expression of NR2B protein in spinal cord were examined. Results the expression of NR2B protein in spinal cord was down-regulated 7 d after intrathecal injection. After intrathecal injection, PWMT in Tat-LK15 group was significantly higher than that in PWTL group and CFA group (P0.01), but PWMT and PWTL in nc Tat-LK15 group had no significant difference compared with CFA group (P0.05). Conclusion Intrathecal injection of Tat-LK15/NR2B siRNA can effectively relieve chronic inflammatory pain induced by CFA in rats.
【作者單位】： 廣州中醫(yī)藥大學(xué)第二附屬醫(yī)院廣東省中醫(yī)院麻醉科;廣州軍區(qū)廣州總醫(yī)院麻醉科;
【基金】：國(guó)家自然科學(xué)基金資助項(xiàng)目(編號(hào):81100817,81371233)
【分類號(hào)】：R402

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