低频电针对紫杉醇诱发周围神经痛大鼠背根神经节TRPV1表达的影响

Effect of Low Frequency Electroacupuncture on the Expression of TRPV1 in Dorsal Root Ganglia of Paclitaxel Induced CIPN Rats

[目的]观察低频电针对紫杉醇(paclitaxel,PTX)化疗药物诱发周围神经病变(chemotherapy-induced peripheral neuropathy,CIPN)导致大鼠50%足底机械缩足反应阈值(paw withdrawal thresholds,PWTs)及背根神经节(dorsal root ganglion,DRG)中瞬时感受器电位香草酸受体1型(transient receptor potential vanilloid 1,TRPV1)通道表达的影响,探讨低频电针干预紫杉醇诱发CIPN的DRG中TRPV1通路的干预作用。[方法]第1部分:健康雄性SD大鼠随机分为溶剂组、紫杉醇组,每组7只。第1、3、5、7天腹腔注射紫杉醇制备CIPN模型。采用von Frey丝测量大鼠第0、2、4、6、8、15、22天右足50%PWTs。第2部分:健康雄性SD大鼠随机分为溶剂组、紫杉醇组、紫杉醇+电针组、紫杉醇+假电针组,每组7只。造模方法同第1部分。电针组于第10天开始治疗,电针参数:双侧"足三里""昆仑"穴,频率2 Hz,强度0.5～1.5 mA,1次/d,30min/次;假电针组予以相同部位针刺,无电流输入。采用von Frey丝测量大鼠第0、2、4、6、8、10、12、14、16、18天右足50%PWTs。用免疫荧光技术检测右侧L4-6 DRG中TRPV1表达。[结果]1.与溶剂组相比,紫杉醇组造模后右足50%PWTs显著降低(P<0.01),说明紫杉醇诱发CIPN模型造模成功;且紫杉醇组右侧L4-6 DRG中TRPV1表达显著增多(P<0.01)。2.电针干预后,紫杉醇+电针组大鼠右足50%PWTs显著提高,而假电针组无明显变化(P<0.01)。3.与紫杉醇组相比,紫杉醇+电针组L4-6 DRG中TRPV1表达有不同程度降低(P<0.01),而假电针组无明显变化(P>0.05)。[结论]低频电针能显著下调大鼠DRG中由紫杉醇所导致的TRPV1过表达,这一作用很可能参与了其抑制紫杉醇诱发大鼠CIPN的作用。

[Objective] To observe the effects of low frequency electroacupuncture(EA) on 50% paw withdrawal thresholds(PWTs) and expression of transient receptor potential vanilloid 1(TRPV1) channels in dorsal root ganglia(DRG) of paclitaxel chemotherapeutics induced CIPN rats. To investigate the effect of low frequency EA on TRPV1 channel expression in DRGs of paclitaxel-induced CIPN rats.[Method] Part one: Healthy male SD rats were randomized and divided into vehicle control group, PTX group(n =7 rats/group). The CIPN model was established by intraperitoneally(i.p.) injecting PTX on 4 alternate days(1, 3, 5, and 7 d). The 50% PWTs were measured by von Frey before the first injection and 1, 3, 5, 7, 14 and 21 d after the injection. Part two:Healthy male SD rats were randomized and divided into vehicle group, PTX group, PTX+EA group, PTX+sham EA groupn=7 rats/each group). The models were established in the same way as described in Part one. Bilateral "Zusanli"(ST36) and "Kunlun"(BL60) were inserted with stainless acupuncture needles. 2 Hz EA with intensities ranging 1~2 mA was delivered for 30 min every day. Sham EA group rats were inserted with needles subcutaneously into ST36 and BL60, but with no electrical discharge. The 50% PWTs were detected by von Frey before the first injection and 1, 3, 5, 7, 9, 11, 13, 15, and17 d after the injection(n=5 rats/group). The levels of TRPV1 expression in the right L4-6 DRG were tested by immunefluorescence staining.[Results] 1.Compared with vehicle group, the 50% PWTs after PTX injection were significantly decreased in the PTX group( P <0.01). PTX treatment significantly increased the expression of TRPV1 expression in the right L4-6 DRG neurons(P<0.01). 2. Low frequency EA but not sham EA significantly alleviated the mechanical hyperalgesia in CIPN rats. 3. Compared with PTX group, PTX+EA group showed significantly decreased TRPV1 expression in L4-6 DRGs( P<0.01).[Conclusions] These results demonstrate that low frequency EA can significantly reduce over expression of TRPV1 in the DRGs of paclitaxel-induced CIPN rats. This mechanism may underlie low frequency EA mediates therapeutic effects on PTX-induced CIPN.