乳铁蛋白对神经病理性痛大鼠脊髓背角PKG活性的影响

Effects of lactoferrin on activity of PKG in spinal dorsal horn in a rat model of neuropathic pain

目的探讨乳铁蛋白对神经病理性痛大鼠脊髓背角cGMP依赖性蛋白激酶（PKG）活性的影响。方法雄性sD大鼠32只，体重200～250g，随机分为4组（n=8）：假手术组仅分离坐骨神经，不结扎，鞘内注射生理盐水10μl＋50％二甲基亚砜（DMSO）10μl；余3组采用结扎坐骨神经的方法制备大鼠神经病理性痛模型，神经病理性痛组鞘内注射生理盐水10μl＋50％DNS010μl；乳铁蛋白组鞘内注射乳铁蛋白100μg＋50％DMS010μl；PKG抑制剂KT5823组鞘内注射乳铁蛋白100pg＋KT582310m。给药后180min内每隔30min以热刺激法测定大鼠缩爪潜伏期，随后处死大鼠取脊髓背角，采用免疫荧光法检测PKG活性，并行定量分析。结果与神经病理性痛组和KT5823组相比，乳铁蛋白组缩爪潜伏期延长，乳铁蛋白组脊髓背角PKG活性升高（P〈0．05）；神经病理性痛组与KT5823组上述指标比较差异无统计学意义（P〉0．05）。结论乳铁蛋白可通过抑制脊髓背角PKG活性减轻大鼠神经病理性痛。

Objective To investigate the effects of lactoferrin on activity of PKG in spinal dorsal horn in a rat model of neuropathic pain （NP）. Methods Thirty-two male SD rats weighing 200-250 g were randomly divided into 4 groups （n = 8 each）： sham operation group （group S）, NP group, lactoferrin group and KT5823 （an inhibitor of PKG） group. Neuropathic pain was produced by placing loosely constrictive ligatures around the common sciatic nerve in group NP, lactoferrin and KT5823, while the sciatic nerve was only exposed but not ligated in groupS. In group S and NP, normal saline 10 /11 ＋ 50% dimethyl sulfoxide （DMSO） 10 μl were injected intrathecally. Lactoferrin 100 μg ＋ 50% DMSO 10 μl were given intrathecally in group lactoferrin. Lactoferrin 100μg ＋ KT5823 10 pl were given intrathecally in group KT5823. The paw withdrawal latency （PWL） to a thermal nociceptive stimulus was measured every 30 min within 180 min after administration. The rats were then sacririced and the spinal cord was removed. The activity of PKG in the spinal dorsal horn was determined by immuno- fluorescence. Results Compared with group NP and KT5823, the PWL was significantly prolonged after administration in group lactoferrin and the PKG activity was significantly increased in group lactoferrin （P 〈 0.05）. There was no significant difference in the parameters mentioned above between group NP and group KT5823 （ P 〉 0.05） . Conclusion Lactoferrin reduces NP by inhibiting the activity of PKG in spinal dorsal horn in rats.