摘要
目的:观察鞘内注射5-HT5AR的小干扰RNA重组腺病毒载体(Ad-5-HT5A-siRNA)前后,化疗痛大鼠脊髓5-HT5AR表达和痛觉过敏的变化情况,探讨5-HT5AR在化疗痛中的作用。
方法:第一部分雄性成年SD大鼠随机分为模型组(n=10)和对照组(n=10),模型组腹腔注射长春新碱,对照组腹腔注射生理盐水,定期测定大鼠的机械痛阈及RT-PCR检测建模结束时大鼠脊髓L4-5段5-HT5AR的mRNA表达。第二部分30只已成功建立化疗痛模型大鼠随机分为三组(n=10),实验组鞘内注射Ad-5-HT5A-siRNA,阴性对照组鞘内注射阴性对照腺病毒(Ad-X-HK),空白对照组鞘内注射生理盐水。鞘内注射后3、7d检测各组L4-5脊髓5-HT5AR的表达,并分别在鞘内注射前及注射后3、5、7d测定机械痛阈。
结果:腹腔注射长春新碱可引起模型组大鼠机械痛阈下降(P<0.01)和脊髓5-HT5AR的mRNA表达增高。而鞘内注射后7d,实验组大鼠5-HT5AR的mRNA表达下降,同时该组大鼠的机械痛阈降低(与阴性对照组、空白对照组比较,P<0.05)。
结论: 5-HT5AR参与了化疗痛的调控过程,其表达增强时可能有减轻化疗痛的作用。
Objective: To investigate the role of 5-HT5A receptors in rats with chemotherapy-evoked hyperalgesia by intrathecal injection of adenovirus-mediated small-interference RNA.
Methods: Adult male SD rats were randomly divided into 2 groups: model group (n=10, intraperitoneal injection of vincristine) and control group (n=10, intraperitoneal injection of normal saline). The mechanical hyperalgesia were measured as the paw withdrawal thresholds(PWT) and the expression of 5-HT5AR mRNA in L4-5 spinal cord were determined by RT-PCR. Thirty rats with chemotherapy-evoked hyperalgesia were randomly divided into 3 groups after the formation of chemotherapy pain model: experimental group, negative control group and blank control group, which respectively were treated with intrathecal injection of Ad-5-HT5AR-siRNA, Ad-X-HK and normal saline. Expressions of 5-HT5AR mRNA and PWT after intrathecal injection were assessed respectively.
Results: Compared with control group, PWT of rats in model group were significantly decreased (P<0.01), and levels of 5-HT5AR mRNA were increased. But after intrathecal injection, expressions of 5-HT5AR were down-regulated in experimental group. Meanwhile, PWT of rats in experimental group were lower than those in negative control group and blank control group (P<0.05).
Conclusions: 5-HT5AR is involved in the mechanism of chemotherapy-evoked hyperalgesia and may has antinociceptive effect.
引文
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