单次迷走神经电刺激对CIPN大鼠有短期治疗作用*

Single Vagus Nerve Electric Stimulation Has Short Term Positive Impact on CIPN Rats

摘要:

目的：探讨颈部迷走神经电刺激能否通过抑制炎症反应发挥治疗化疗诱发周围神经病(CIPN)的作用。方法：72只SD大鼠随机分为迷走神经刺激组(VNS组)(n=36) 和假手术组(Sham组,n=36),腹腔注射紫杉醇建立CIPN模型,建模成功后于D28天全麻后给予右侧颈部迷走神经电刺激(VNS组)或仅放置电极不刺激(Sham组)。分别于D0、D28、D29和D35测量大鼠的4g和15g von frey纤维刺激缩足率及热痛阈,于D28、D29和D35取L4-6背根神经节(DRG),Western blot法和免疫组化法检测NF-κB、TNF-a、IL-10表达。结果：VNS组D29和D35的15g机械刺激下缩足率和热痛阈与D0相比差异均无统计学意义(P>0.05),与D28相比差异具有显著统计学意义(缩足率10.83%,5% vs 39.17%,热痛阈10.66s,10.63s vs 6.14s,P＜0.001)。D29和D35 VNS组15g机械刺激下缩足率显著低于Sham组(10.83% vs 35%；5% vs 28.33%,P＜0.001),热痛阈显著高于Sham组(10.66s vs 6.35s；10.63s vs 6.35s,P＜0.001)。D28和D29 VNS组DRG中IL-10表达高于Sham组(Western blot,免疫组化)(P＜0.05),D28 VNS组DRG中NF-κB表达低于Sham组(Western blot)(P＜0.05)。结论：单次颈部迷走神经刺激有助于短期内改善CIPN大鼠疼痛行为学,提高DRG内IL-10,降低DRG内NF-κB。

Abstract:

Objective: To investigate whether cervical vagus nerve electric stimulation could treat chemotherapy induced peripheral neuropathy(CIPN) by inhibiting inflammation. Methods: 72 SD rats were randomly divided into vagus nerve stimulation group(VNS group)(n=36) and sham group(n=36). After the CIPN model was established by intraperitoneal injection of paclitaxel, on D28 electric stimulation of the right cervical vagus nerve was given (VNS group),or only electrode was put on the right cervical vagus nerve(sham group). 4g and 15 g paw withdrawal rates, heat threshold of rats was recorded on D28, D29 and D35. L4-6 dorsal root ganglion(DRG) was obtained on D28, D29 and D35, NF-κB、TNF-? and IL-10 was measured by Western blot and immunohistochemical staining. Results: In VNS group, there was no significant difference between the 15 g paw withdrawal rates and heat threshold on D29, D35 and D0(P>0.05), the 15 g paw withdrawal rates and heat threshold on D29, D35 was significantly improved compared with D28(P＜0.001). The 15 g paw withdrawal rates in VNS group was significantly lower than in sham group, the heat threshold was significantly higher than in sham group(P＜0.001). IL-10 in the DRG of VNS group was higher than sham group on D28 and D29(Western blot and immunohistochemical staining)(P＜0.05), NF-κB in the DRG of VNS group was lower than sham group on D28(Western blot)(P＜0.05). Conclusion: Single cervical vagus nerve electric stimulation could improve the pain behavior of CIPN rats, increase IL-10 and inhibit NF-κB in DRG and protect neurons in DRG in short term.