天麻素通过下调Nav1.6通道表达缓解糖尿病神经病理性疼痛的研究

Gastrodin Alleviated Diabetic Neuropathic Pain via Downregulating the Expression of Nav1.6 in Rats

目的:探究天麻素对Ⅱ型糖尿病神经病理性痛的镇痛作用以及天麻素对背根神经节Nav1.6通道的表达调控作用。方法:将60只雄性SD大鼠随机分为空白对照组、糖尿病组和天麻素处理组(10 mg·kg^(-1)·d^(-1))。通过高脂饮食喂养4周,低剂量腹腔注射STZ(30 mg·kg^(-1))的方法构建Ⅱ型糖尿病神经病理性痛大鼠模型,利用痛行为学检测观察各组大鼠的机械刺激足缩反应阈值变化,采用免疫荧光组织化学及Western blot方法观察各组大鼠背根神经节上Nav1.6通道的表达变化。结果:与空白对照组相比,糖尿病模型大鼠出现显著的机械刺激疼痛阈值下降(P<0.05),且模型组大鼠背根神经节神经元上的Nav1.6通道表达上调(P<0.05)。与糖尿病组相比,连续腹腔注射天麻素3天、7天、14天后,模型动物的疼痛明显缓解(P<0.05),另外天麻素可以翻转背根神经节上Nav1.6通道的高表达(P<0.05)。结论:天麻素可能通过降低Nav1.6通道的表达来缓解Ⅱ型糖尿病神经病理性疼痛,从而为天麻素缓解糖尿病神经病理性疼痛提供新的理论依据。

Objective:To investigate the inhibitory effect of gastrodin on allodynia in diabetic neuropathic pain and its mechanisms.Methods:144 male SD rats were randomly divided into three groups:control group,diabetes group and gastrodin treatment group(10 mg·kg^(-1)·d^(-1)).TypeⅡDiabetic rats were fed high fat diet for 4 weeks and intraperitoneally injected with low-dose streptozotocin(STZ)(30 mg·kg^(-1)).The paw withdrawal mechanical threshold(PWMT)was detected to reflect the pain behavioral changes.The expression of Nav1.6 was observed by immunofluorescence histochemistry and Western blot analysis.Results:Compared with control rats,typeⅡdiabetic rats showed significant pain sensitization and lower PWMT(P<0.05).Upregulated expression of Nav1.6 channel was detected on dorsal root ganglion(DRG)neurons from these painful diabetic rats(P<0.05).After continuous injection of gastrodin for 3 days,7 days and 14 days,the allodynia of diabetic rats was significantly relieved(P<0.05).Moreover,gastrodin could reverse the overexpression of Nav1.6 on dorsal root ganglion neurons(P<0.05).Conclusion:Gastrodin could alleviate diabetic neuropathic pain by downregulating the overexpression of Nav1.6.This research may provide new data for clinical therapy in diabetic neuropathic pain.