三硝基苯三磷酸腺苷鞘内注射对大鼠内脏高敏感性的影响

Effect of Intrathecal Injection of Trinitrophenyl Adenosine Triphosphate on Visceral Hypersensitivity in Rats

背景:P2X受体在感觉神经元中表达丰富,近年研究表明其在伤害性信息的传导过程中起有重要作用。目的:研究选择性P2X受体拮抗剂三硝基苯三磷酸腺苷(TNP-ATP)鞘内注射对大鼠内脏高敏感性的影响,了解P2X受体与内脏高敏感性的关系。方法:30只健康Wistar大鼠随机分为5组,每组6只。以慢性避水应激建立内脏高敏感模型(S组),以假应激作为对照(C组),分别予鞘内注射0.9%NaCl溶液10μl(SNaCl组和CNaCl组)、TNP-ATP50μg/10μ1(ST50组和CT50组)和TNP-ATP25μg/10μl(ST25组)。以结直肠扩张(CRD)时的腹壁肌电图内脏运动反射(VMR)幅度值和脊髓灰质c-fos蛋白的表达为指标观察内脏敏感性的变化。结果:鞘内注射后,SNaCl组CRD时的VMR幅度值(40mmHg:P<0.05;60和80mmHg:P<0.01)和脊髓灰质c-fos免疫阳性细胞数(1区:P<0.01;3区:P<0.05)较CNaCl组显著增加;ST50组VMR幅度值(40和80mmHg:P<0.05;60mmHg:P<0.01)和c-fos免疫阳性细胞数(1区和3区:P<0.05)较SNaCl组显著降低;ST25组VMR幅度值和c-fos免疫阳性细胞数无明显变化。结论:TNP-ATP50μg/10μl鞘内注射可降低大鼠的内脏高敏感性,提示在心理应激所致的内脏高敏感过程中有P2X受体参与。

Background： P2X receptors are richly expressed in sensory neurons. It was shown in recent years that P2X receptors play an important role in the transmission of nociceptive information. Aims： To investigate the effect of intrathecal injection of 2＇ ,3＇-O-trinitrophenyl adenosine 5 ＇-triphosphate （TNP-ATP）, a selective P2X receptor antagonist, on visceral hypersensitivity in rats, so as to clarify the correlation between P2X receptors and visceral hypersensitivity. Methods： Thirty healthy Wistar rats were randomly divided into 5 groups, 6 rats in each group. Visceral hypersensitivity model was established by chronic water avoidance stress （S groups） and sham water avoidance stress was used in control groups （C groups）. SNaCl and CNaCl groups were injected intrathecally with 10μl 0.9% NaCl; SNaCl and CNaCl groups were injected with TNP-ATP 50μg/10 μl, and ST25 group with TNPoATP 25 μg/10 μl. Abdominal wall electromyogram was taken and magnitude of visceromotor response （VMR） was calculated during colorectal distention （CRD）. Magnitude of VMR and c-fos protein expression in gray substance of spinal cord measured immunohistochemically were used to observe the changes of visceral hypersensitivity. Results： After intrathecal injection, the magnitude of VMR during CRD （40 mm Hg： P〈0.05; 60 and 80 mm Hg： P〈0.01） and c-fos protein expression in gray substance of spinal cord （area 1： P〈0.01; area 3： P〈0.05） were significantly higher in SNaCl group than those in CNaCl group. The magnitude of VMR （40 and 80 mm Hg： P〈 0.05; 60 mm Hg： P〈0.01） and c-fos protein expression （area 1 and area 3： P〈0.05） were significantly lower in SNaCl group than those in SNaCl group. The differences of VMR magnitude and c-fos protein expression between ST24 and SNaCl groups and ST25 and ST50 groups were not significant. Conclusions： Intrathecal injection of TNPoATP 50μg/10μl can decrease visceral hypersensitivity in rats and it suggests that P2X receptors may be involved in the formation of visceral hypersensitivity induced by psychological stress.