阻断Nav1.8表达对大鼠内脏高敏感性影响的研究

目的通过阻断Nav1．8钠通道的表达研究其对内脏高敏感性的影响。方法以新生大鼠直肠内气囊扩张法制成动物模型，连续3d，每天2次鞘内注射Nav1．8钠通道反义寡核苷酸以阻断Nav1．8的表达，并以行为学腹部收缩反射（AWR）评分和脊髓c-Fos的表达为指标观察大鼠内脏高敏感的改变情况。结果鞘内注射Nav1．8钠通道反义寡核苷酸使大鼠Nav1．8 mRNA的表达下降。行为学检测发现造模组大鼠AWR评分下降，脊髓c-Fos样免疫反应（c-FLI）阳性细胞总数减少，主要是1区和3区的细胞数减少，而注射错配寡核苷酸组无明显改变。对照组则不论注射错配寡核苷酸或反义寡核苷酸AWR评分和脊髓c—FLI阳性细胞数均无明显改变。结论鞘内注射反义寡核苷酸阻断Nav1．8的表达，可以降低造模大鼠内脏高敏感状态。

Inhibition of visceral hypersensitivity in rats by decreased expression of Nav1. 8

Objective To investigate the effect of inhibiting the expression of Navl. 8 sodium channels by an antisense oligodeoxynudeotide(ODN) on visceral hypersensitivity. Methods The visceral hypersensitivity animal models induced by giving neonatal Sprague-Dawley rats colorectal distention(CRD) after postnatal days 8, 10 and 12. Animals were injected intrathecally either Navl. 8 antisense ODN (research group) or mismatch ODN (control group) twice a day for 3 days at the 8th week. After that, the expression of Navl. 8 in each group was examined by RT-PCR, and abdomiral withdrawal reflex(AWR) score and spinal c-Fos expression were evaluated to assess whether the intervention can relieve the visceral hypersensitivity. Results After intrathecal injection with the antisense ODN, the expression of Navl. 8 in each group decreased.AWR score and the number of c-Fos positive neurons in the spinal cord, especially in the area 1 and 3, decreased in the model group, while they did not change in the control group. Conclusions Interventing the expression of Nav1.8 may relieve the visceral hypersensitivity in this model of irritable bowel syndrome.