肠吉泰对内脏高敏大鼠电压门控钠通道Nav1.8和神经生长因子的影响

Effect of Chang Ji Tai on voltage-gated sodium channel Nav1.8 andnerve growth factor in the rats with visceral hypersensitivity

[目的]观察肠吉泰对内脏高敏大鼠电压门控钠通道(VGSC)Nav1.8和神经生长因子(NGF)的影响。[方法]40只新生SD大鼠随机分成正常组、模型组、肠吉泰A组和B组4组;用醋酸刺激法建立内脏高敏大鼠模型;肠吉泰A组和B组分别每日予肠吉泰30g/kg和50g/kg灌胃,正常组和模型组予等量去离子水灌胃;4周后,采用直肠气囊扩张法评估内脏敏感性;取L6～S2脊髓背根神经节和直肠组织,采用RT-PCR和ELISA法分别检测Nav1.8 mRNA和NGF含量。[结果]与正常组相比,模型组大鼠内脏敏感性增高(P<0.01),Nav1.8 mRNA和NGF含量均明显增高(P<0.05);肠吉泰B组与正常组相比,内脏敏感性、Nav1.8 mRNA和NGF均差异无统计学意义;与模型组比,P<0.01或P<0.05。[结论]高剂量肠吉泰可能通过降低肠道NGF和脊髓背根神经节Nav1.8来降低内脏敏感性。

[Objective]To observe the effect of Chang Ji Tai（CJT）on voltage-gated sodium channel Nav1.8 in dorsal root ganglia and nerve growth factor in the rectum of the rats with visceral hypersensitivity.[Methods]Fourty neonatal Sprague-Dawley rats were randomly divided into 4 groups：normal control group,model control group,CJT group A and CJT group B.Visceral hypersensitivity model was induced by intrarectal acetic acid irritation in the latter 3 groups.0.2ml of 0.5% acetic acid was injected into rectum through epidural catheter everyday for 3 weeks.Then CJT with concentrations of 30g/kg and 50g/kg were administered intragastrically everyday in CJT group A and B respectively while equivalent deionized water was administered intragastrically in normal control group and model control group.After 4-week treatment,rectal balloon distension was applied to evaluate visceral hypersensitivity.The pressure values inducing rat abdominal retraction and back hunch were recorded.Each value was repeated three times with a 5-minute interval and the average value was calculated.L6～S2 dorsal root ganglia and 1 cm rectum tissue were isolated for Nav1.8 mRNA and nerve growth factor measurement respectively.Real-time polymerase chain reaction（RT-PCR）and enzyme linked immunosorbent assay（ELISA）were applied to measure Nav1.8 mRNA and nerve growth factor respectively.[Results]Compared to the normal control group,the pressures inducing abdominal retraction and back hunch were significantly lower in model control group（P〈0.01）and CJT group A（P=0.022 and P=0.021）while the dorsal root ganglia Nav1.8 mRNA and the rectal nerve growth factor levels were significantly higher in model control group（P=0.023 and P=0.017）and CJT group A（P=0.039 and P=0.016）.The pressures inducing abdominal retraction and back hunch in CJT group B were similar to those in normal control group（P=0.744 and P=0.440）.There were no significant differences between CJT group B and normal control group in the levels of Nav1.8 mRNA（P=0.998）and nerve growth factor（P=0.920）.[Conclusion]High dosage CJT could reduce the visceral hypersensitivity by decreasing the levels of dorsal root ganglia Nav1.8 mRNA and rectal nerve growth factor.