鞘内注射白介素-10对慢性内脏痛敏大鼠脊髓促炎细胞因子的影响

Influence of Intrathecal Injection with Interleukin-10 on the Pro-inflammatory Cytokines of Spinal Cord on Rats with Chronic Visceral Hyperalgesia

目的探讨鞘内注射白介素-10(Interleukin-10,IL-10)在慢性内脏痛敏(Chronic Visceral Hyperalgesia,CVH)大鼠中的作用及其可能机制。方法新生雄性SD(Sprague-Dawley)大鼠随机均分为三组:对照组(Control组)、慢性内脏痛敏模型组(CVH组)和模型鞘内注射IL-10组(CVH+IL-10组);CVH组和CVH+IL-10组采用新生期结直肠扩张(Colorectal distension,CRD)建立慢性内脏痛敏模型。待大鼠成年后,通过腹外斜肌放电(Electromyogram,EMG)实验评估其内脏痛觉敏感性。CVH+IL-10组连续3天鞘内注射100 ng IL-10,Control组和CVH组给予同体积的生理盐水后,测定腹外斜肌放电幅值;采用荧光定量PCR实验检测脊髓背角TNF-α、IL-1β及IL-6 mRNA表达水平。结果与Control组相比,CVH组大鼠的腹外斜肌放电幅值显著升高(P<0.05);鞘内注射IL-10能够显著降低CVH大鼠腹外斜肌放电幅值(P<0.05);CVH组大鼠脊髓背角中TNF-α、IL-1β和IL-6 mRNA表达水平相比Control组显著升高(P<0.05);鞘内注射IL-10后,脊髓背角TNF-α、IL-1β和IL-6 mRNA表达水平显著下降(P<0.05)。结论鞘内注射IL-10对慢性内脏痛敏有一定的缓解作用,其作用机制可能与抑制脊髓背角促炎细胞因子的合成有关。

OBJECTIVE This study aimed to investigate the role and the underlying mechanism of Interleukin-10 in chronic visceral hyperalgesia.METHODS Neonatal male Sprague Dawley rats were randomly and equally assigned into three groups:Control group,CVH group and CVH+IL-10 group.The CVH group and CVH+IL-10 group were induced by neonatal colorectal distension.The electromyogram was used to evaluate the visceral nociceptive sensitivity of adult rats.The CVH+IL-10 group was intrathecal injection 100ng IL-10 for 3 consecutive days.The Control and CVH groups were treated with normal saline in the same volume.The electromyogram was measured after injection.The mRNA expression level of IL-1β,IL-6 and TNF-αin spinal dorsal horn were detected by Real-time PCR.RESULTS Compared to the Control group,the electromyogram of rats in CVH group was significantly increased(P<0.05).Intrathecal injection of IL-10 could reduce the EMG of CVH rats significantly(P<0.05).In comparison to the Control group,the mRNA expression levels of TNF-α,IL-1βand IL-6 in spinal dorsal horn of rats in CVH group were high(P<0.05).However,the mRNA expression levels of TNF-α,IL-1βand IL-6 were significantly decreased after intrathecal injection of IL-10(P<0.05).CONCLUSION Intrathecal injection of IL-10 can alleviate chronic visceral hyperalgesia.The mechanism may be related to regulate the synthesis of pro-inflammatory cytokines in the dorsal horn of the spinal cord.