摘要
目的 探讨鞘内注射反义、正义PKCγ寡核苷酸(PKCγ-ASODN、PKCγ-SODN)对慢性神经痛大鼠的镇痛作用及其机制。方法 24只雌性SD大鼠建立慢性坐骨神经痛(CCI)模型,鞘内置管后随机分为4组:CCI+无菌生理盐水鞘内注射组(C组);CCI+PKCγ-SODN 20μg鞘内注射组(S组);CCI+PKCγ-ASODN 5μg鞘内注射组(A1组);CCI+PKCγ-ASODN 20μg鞘内注射组(A2组),每组6只。除C组外,其余三组均于鞘内注入相应剂量的PKC7γ-SODN或-ASODN,每日1次,连续6 d,采用VonFrev hairs检测术侧机械缩爪阈值变化,Western blot法检测脊髓PKCγ、PKCα蛋白质表达。结果 与结扎术前比较,机械缩爪阈值S组注药后2、4、6 d降低,A1组注药后2 d天降低(P<0.01),A2组注药后4 d升高(P<0.05或0.01);与C组比较,A1组注药后4、6d及A2组注药后2、4、6 d升高(P<0.01);与A1组比较,A2组注药后2、4 d升高(P<0.01)。与C组比较,A1、A2组PKCγ蛋白质表达丰度降低(P<0.01),而S组PKCγ蛋白质及S、A1、A2组PKCα蛋白质表达丰度差异无统计学意义(P>0.05)。结论 鞘内注射PKCγ-ASODN可抑制慢性神经痛大鼠的痛觉过敏,该作用与PKCγ蛋白质活性降低,表达量下调有关。
Objective To evaluate the effect of PKCγ antisense oligonucleotide (ASODN) administered intrathecally on the hyperalgesia induced by chronic constructive injury (CCI) and to investigate the underlying mechanism.Methods Twenty four female SD rats weighing 150-180 g were used. CCI was produced by 4 loose ligatures placed on the right sciatic nerve. A catheter was inserted into subarachnoid space at L3-4 for intrathecal drug or normal saline(NS) administration. Three days after intrathecal catheter implantation when the function of the animal's lower limbs recovered, NS or drug was injected through the catheter every day for 6 days. Then the animals were decapitated and the lumbar segment (L2-6 ) of the spinal cord was removed. The animals were randomly divided into 4 groups of 6 animals : Ⅰ CCI + NS (group C); Ⅱ CCI + PKCγ sense oligonucleotide (SOON) 20 μg (group S); Ⅲ CCI + ASODN 5 μg (group A1) and Ⅳ CCI + ASODN 20 μg(group A2). The mechanical withdrawal threshold was assessed by Von Frey hair stimulation. The expression of PKCγ and PKCa protein in the spinal cord was determined using Western blot. Results The threshold to Von Frey hair stimulation was significantly reduced after sciatic nerve ligation. Intrathecal ASODN administration significantly reduced the hyperalgesia induced by CCI in group A1 and A2 in a dose-dependent manner as compared with group C. The expression of PKCy protein in lumbar spinal cord was significantly lower in group A1 and A2 than in group C. There was no significant difference in PKCa protein expression among the four groups. Conclusion The hyperalgesia induced by CCI can be decreased by intrathecal administration of PKCy antisense oligonucleotide. The reduction in expression of PKCy protein may be involved in the mechanism.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2005年第1期52-54,共3页
Chinese Journal of Anesthesiology
基金
湖北省自然科学基金资助(2002AA301D09)
