星形胶质细胞内的三羧酸循环在福尔马林诱导的脊髓中枢敏化中的作用
发布时间:2018-05-14 06:58
本文选题:星形胶质细胞 + 三羧酸循环 ; 参考:《兰州大学》2014年硕士论文
【摘要】:目的通过观察福尔马林致炎大鼠鞘内给药后的行为学变化,探讨星形胶质细胞内的三羧酸循环在福尔马林诱导的脊髓中枢敏化中的作用。 方法建立炎性痛动物模型,通过行为学检测观察了福尔马林(5%,50μ1)致炎大鼠鞘内给予1nmol/10μl氟代柠檬酸(fluorocitrate,FC)和(或)500nomol/10μl谷氨酸(L-glutamate,Glu)后大鼠行为学变化情况。具体如下:(1)福尔马林炎性持续性痛模型:选择鞘内置管术后5d恢复良好的大鼠右后肢足底中心皮下注射(s.c.)5%的福尔马林50μl。(2)鞘内给药:a.福尔马林炎性持续性痛急性期:对照组:福尔马林注射前20分钟,分别鞘内注射①12%DMSO(n=3)②谷氨酸(500nmol/10μl,n=3);实验组:③福尔马林注射前20分钟,鞘内注射FC(1nmol/10μl, n=6),④鞘内注射500nmol/10μl Glu10分钟后,再次鞘内注射1nmol/10μl FC,20分钟后右后肢足底注射福尔马林(n=6)。推进速度为0.5μl/s,注射福尔马林后即刻将实验大鼠放入实验箱进行行为学测试。b.福尔马林炎性持续性痛慢性期:①福尔马林注射前20分钟,分别鞘内注射12%DMSO(n=3).FC(1nmol/10μl,n=6),并在福尔马林注射后3h、6h、1d、2d、3d、4d进行行为学检测;②福尔马林注射前20分钟,注射后1d,2d,连续3次分别鞘内注射12%DMSO(n=3).FC(1nmol/10μl, n=6),并在福尔马林注射后1d、2d、3d、5d、7d、9d、14d进行行为学检测;③福尔马林注射后9d,分别鞘内注射12%DMS0(n=3).FC(1nmol/10μl, n=6),并在福尔马林注射后1d、3d、5d、7d、9d(0h)、9d(3h)、9d(6h)、10d、11d、14d进行行为学检测;④福尔马林注射后9d、10d、11d,分别鞘内注射12%DMSO(n=3).FC(1nmol/10μ l,n=6),并在福尔马林注射后1d、3d、5d、7d、9d、10d、11d、12d、13d、14d进行行为学检测。 结果(1)鞘内给予FC对炎性痛大鼠自发伤害性行为(舔咬爪和缩腿反射)有抑制作用,而鞘内给予Glu对此作用产生部分的翻转效应。 (2)在急性期:与对照组相比,单次(福尔马林注射20min前)鞘内给予FC能够在1-3内抑制大鼠的机械痛敏,并在第1天显著抑制大鼠机械痛敏(P≤0.01);多次(福尔马林注射20min前和注射后1d、2d连续3天)鞘内注射FC能够在1-7天内抑制大鼠的同侧和对侧的机械痛敏,在第5天显著抑制大鼠同侧机械痛敏(P≤0.01),在第3天显著抑制大鼠对侧机械痛敏(P≤0.01)。在慢性期:与对照组相比,单次(福尔马林注射后第9天)鞘内注射FC3小时时能够抑制大鼠的同侧和对侧的机械痛敏(P≤0.05),但在6小时时其机械痛敏恢复;多次(福尔马林注射后9d、l0d、l1d连续3天)鞘内注射FC能够对同侧和对侧的机械痛敏产生瞬时的抑制的作用。 结论鞘内注射氟代柠檬酸能显著降低炎性痛大鼠的自发伤害性行为及诱发伤害性行为,而谷氨酸能够部分翻转此作用,提示星形胶质细胞内三羧酸循环在脊髓中枢敏化中起着重要作用。
[Abstract]:Aim to investigate the role of tricarboxylic acid cycle in astrocytes in formalin-induced spinal central sensitization by observing the behavioral changes after intrathecal administration of formalin-induced inflammatory rats. Methods the animal model of inflammatory pain was established and the behavioral changes of rats induced by 1nmol/10 渭 l fluorocitrate (FCU) and (or 500nomol- / 10 渭 l glutamate) were observed by behavioral examination. The model of inflammatory persistent pain in formalin: the right hind limb of rats with good recovery 5 days after intrathecal catheterization was subcutaneously injected with 5% formalin 50 渭 l. Acute phase of continuous pain in formalin: control group: 20 minutes before formalin injection, intrathecal injection of 112%DMSO(n=3)2 glutamate 500 nmol / 10 渭 l / L, FC(1nmol/10 渭 l 20 minutes before injection, 500nmol/10 渭 l Glu10 minutes after intrathecal injection of 500nmol/10 渭 l, respectively, in the experimental group, the control group was given intrathecal injection of FC(1nmol/10 渭 l, and the control group received intrathecal injection of Glutamic acid 500 nmol / 10 渭 l / L, respectively, and the control group received intrathecal injection of 500nmol/10 渭 l Glu10. After 20 minutes of intrathecal injection of 1nmol/10 渭 l FCU, the right hind limb was injected with formalin in the sole of the foot. The propelling speed was 0.5 渭 l / s. Immediately after formalin injection, the experimental rats were put into the experimental box for behavioral test. 20 minutes before chronic injection of 12%DMSO(n=3).FC(1nmol/10 渭 l, 12%DMSO(n=3).FC(1nmol/10 渭 l was injected intrathecally, and the behavior of formalin was measured 20 minutes before injection, 3 hours after injection of formalin, 1 hour after injection, 1 hour after injection, 2 days after injection, 2 minutes before injection of formalin, 20 minutes before injection of formalin, 1 hour after injection, 2 minutes after injection of formalin, 20 minutes before injection of formalin. 娉ㄥ皠鍚,
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