线粒体抗氧化对神经病理性疼痛大鼠TRPV1表达的影响
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摘要
目的探讨线粒体抗氧化治疗对神经病理性疼痛(NP)大鼠脊髓水平瞬时感受器电位香草酸受体1(TRPV1)表达的影响。方法清洁级雄性SD大鼠120只,采用随机数字表法分为3组:假手术组(Sham组,n=40)、神经病理性疼痛组(NP组,n=40)、抗氧化治疗组(MT组,n=40)。NP组和MT组采用慢性坐骨神经结扎(CCI)制备NP模型。术后第7天MT组腹腔注射三苯基磷阳离子结合抗氧化剂(MT)0.7 mg/kg, Sham组和NP组腹腔注射生理盐水,1次/d,连续14 d。术前及术后第3、7、14、21天时测定机械缩足反应阈(MWT)和热缩足潜伏期(TWL),评价疼痛行为。术前及术后第3、7、14、21天取大鼠L4-6节段脊髓,采用Western blot法测定TRPV1的表达。结果与Sham组比较,NP组大鼠术后第3、7、14、21天MWT明显降低(P<0.05),TWL明显缩短(P<0.05),MT组大鼠术后第3、7天MWT明显降低(P<0.05),TWL明显缩短(P<0.05);与NP组比较,MT组大鼠术后第14、21天MWT明显升高(P<0.05),TWL明显延长(P<0.05)。与Sham组比较,NP组大鼠脊髓TRPV1表达在术后第7、14、21天明显增加(P<0.05), MT组大鼠术后第7天脊髓TRPV1表达明显增加(P<0.05);与NP组比较,MT组大鼠脊髓TRPV1在术后第14、21天明显降低(P<0.05)。结论线粒体抗氧化可以缓解NP大鼠的疼痛行为,可能与降低脊髓水平TRPV1表达有关。
Objective To evaluate the effect of mitochondria-targeted antioxidant on transient receptor potential cation channel,subfamily V, member 1(TRPV1) expression in neuropathic pain(NP) rats. Methods 120 male Sprague-Dawley rats were randomly divided into 3 groups(n=40 each) using a random number table:sham operation group(Sham group),neuropathic pain group(NP group), mitochondrial antioxidant treatment group(MT group). Neuropathic pain was induced by chronic constriction injury in NP and MT groups. Starting from 7 th day after operation, mito-tempo(triphenylphosphine cation combined with antioxidant) 0.7 mg/kg in 1 ml of normal saline was injected intraperitoneally once a day for 14 consecutive days in MT group, and the equal volume of normal saline was given once a day for 14 consecutive days in Sham and NP groups. On 1 day before operation and 3,7,14 and 21 days after operation, the mechanical paw withdrawal threshold(MWT) and thermal paw withdrawal latency(TWL) were measured. Lumbar 4-6 segments of the spinal cord were harvested to detect the expression of TRPV1(by Western blot) before operation and on days 3,7,14 and 21 after operation. Results Compared with group Sham, the MWT and TWL in NP group were significantly decreased on the 3 rd,7 th,14 th and 21 st day after operation(P<0.05), the MWT and TWL in MT group were significantly decreased on the 3 rd and 7 th day after operation(P<0.05); Compared with group NP, the MWT and TWL in MT group were significantly increased on the 14 th and 21 st day after operation(P<0.05). Compared with group Sham,the expression of TRPV1 in NP group was significantly increased on the 7 th, 14 th and 21 st day after operation(P<0.05),the expression of TRPV1 in MT group was significantly increased on the 7 th day after operation(P<0.05); Compared with group NP, TRPV1 expression in MT group was significantly deceased on the 14 th and 21 st day after operation(P<0.05). Conclusion The mechanism by which mitochondrial antioxidant treatment increases behavior threshold may be related to TRPV1 expression reduction.
Objective To evaluate the effect of mitochondria-targeted antioxidant on transient receptor potential cation channel,subfamily V, member 1(TRPV1) expression in neuropathic pain(NP) rats. Methods 120 male Sprague-Dawley rats were randomly divided into 3 groups(n=40 each) using a random number table:sham operation group(Sham group),neuropathic pain group(NP group), mitochondrial antioxidant treatment group(MT group). Neuropathic pain was induced by chronic constriction injury in NP and MT groups. Starting from 7 th day after operation, mito-tempo(triphenylphosphine cation combined with antioxidant) 0.7 mg/kg in 1 ml of normal saline was injected intraperitoneally once a day for 14 consecutive days in MT group, and the equal volume of normal saline was given once a day for 14 consecutive days in Sham and NP groups. On 1 day before operation and 3,7,14 and 21 days after operation, the mechanical paw withdrawal threshold(MWT) and thermal paw withdrawal latency(TWL) were measured. Lumbar 4-6 segments of the spinal cord were harvested to detect the expression of TRPV1(by Western blot) before operation and on days 3,7,14 and 21 after operation. Results Compared with group Sham, the MWT and TWL in NP group were significantly decreased on the 3 rd,7 th,14 th and 21 st day after operation(P<0.05), the MWT and TWL in MT group were significantly decreased on the 3 rd and 7 th day after operation(P<0.05); Compared with group NP, the MWT and TWL in MT group were significantly increased on the 14 th and 21 st day after operation(P<0.05). Compared with group Sham,the expression of TRPV1 in NP group was significantly increased on the 7 th, 14 th and 21 st day after operation(P<0.05),the expression of TRPV1 in MT group was significantly increased on the 7 th day after operation(P<0.05); Compared with group NP, TRPV1 expression in MT group was significantly deceased on the 14 th and 21 st day after operation(P<0.05). Conclusion The mechanism by which mitochondrial antioxidant treatment increases behavior threshold may be related to TRPV1 expression reduction.
引文
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[8] Li Y,Adamek P,Zhang H,et al.The cancer chemotherapeutic paclitaxel increases human and rodent sensory neuron responses to TRPV1 by activation of TLR4[J].J Neurosci,2015,35(39):13487-500.
[9] Yamamoto K,Chiba N,Chiba T,et al.Transient receptor potential ankyrin 1 that is induced in dorsal root ganglion neurons contributes to acute cold hypersensitivity after oxaliplatin administration[J].Mol Pain,2015,11(1):1-11.
[10] Rahbardar M G,Amin B,Mehri S,et al.Rosmarinic acid attenuates development and existing pain in a rat model of neuropathic pain:An evidence of anti-oxidative and anti-inflammatory effects[J].Phytomedicine,2018,40:59-67.
[11] Lis K,Grygorowicz T,Cudna A,et al.Inhibition of TNF reduces mechanical orofacial hyperalgesia induced by complete Freund's adjuvant by a TRPV1-dependent mechanism in mice[J].Pharmacol Rep,2017,69(6):1380-5.
[2] Zhan L,Li R,Sun Y,et al.Effect of mito-TEMPO,a mitochondria-targeted antioxidant,in rats with neuropathic pain[J].Neuro Report,2018,29(15):1275-81.
[3] Utsumi D,Matsumoto K,Tsukahara T,et al.Transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 contribute to the progression of colonic inflammation in dextran sulfate sodium-induced colitis in mice:Links to calcitonin gene-related peptide and substance P[J].J Pharmacol Sci,2018,136(3):121-32.
[4] Bennett G J,Xie Y K.A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man[J].Pain,1988,33(1):87-107.
[5] Gandhi S,Abramov A Y.Mechanism of oxidative stress in neurodegeneration[J].Oxid Med Cell Longev,2012,2012(3):428010.
[6] Mart?Nez-Revelles S,Garc?A-Redondo A B,Avendaňo M S,et al.Lysyl oxidase induces vascular oxidative stress and contributes to arterial stiffness and abnormal elastin structure in hypertension:role of p38MAPK[J].Antioxid Redox Signal,2017,27(7):379-97.
[7] Chiba T,Oka Y,Sashida H,et al.Vincristine-induced peripheral neuropathic pain and expression of transient receptor potential vanilloid 1 in rat[J].J Pharmacol Sci,2017,133(4):254-60.
[8] Li Y,Adamek P,Zhang H,et al.The cancer chemotherapeutic paclitaxel increases human and rodent sensory neuron responses to TRPV1 by activation of TLR4[J].J Neurosci,2015,35(39):13487-500.
[9] Yamamoto K,Chiba N,Chiba T,et al.Transient receptor potential ankyrin 1 that is induced in dorsal root ganglion neurons contributes to acute cold hypersensitivity after oxaliplatin administration[J].Mol Pain,2015,11(1):1-11.
[10] Rahbardar M G,Amin B,Mehri S,et al.Rosmarinic acid attenuates development and existing pain in a rat model of neuropathic pain:An evidence of anti-oxidative and anti-inflammatory effects[J].Phytomedicine,2018,40:59-67.
[11] Lis K,Grygorowicz T,Cudna A,et al.Inhibition of TNF reduces mechanical orofacial hyperalgesia induced by complete Freund's adjuvant by a TRPV1-dependent mechanism in mice[J].Pharmacol Rep,2017,69(6):1380-5.