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目的:观察血红素加氧酶-1(Heme oxygenase-1,HO-1)在神经病理性疼痛(Neuropathic pain,NP)大鼠脊髓中的表达水平变化,研究HO-1激动剂原卟啉钴(cobalt protoporphyrinⅨ,COPP)对神经病理性疼痛的调节作用及其可能机制。方法:本实验采用保留性坐骨神经损伤(spared nerve injury,SNI)模型。雄性SD大鼠随机分为3组:Sham+Vehicle组、SNI+Vehicle和SNI+COPP组。术后第一天开始,Sham+Vehicle组和SNI+Vehicle组腹腔注射1%DMSO 10 ml/kg,SNI+COPP组腹腔注射0.1%COPP 10 mg/kg,均连续给药7天。各组分别于术前、术后第3(D3)、7(D7)和14(D14)天测定大鼠50%的机械刺激缩足阈值(Paw withdrawl threshold,PWT)。于术后D7、D14处死,取大鼠L4-6节段术侧脊髓,采用western blot检测脊髓中HO-1、μ受体(μ-opioid receptor,MOR)和δ受体(δ-opioid receptor,DOR)的表达量变化。结果:(1)各组术前术侧PWT无明显统计学差异(P>0.05);术后SNI+Vehicle组和SNI+COPP组较Sham+Vehicle组相比,在相同时间点术侧PWT值显著下降(P<0.05);与SNI+Vehicle组相比,SNI+COPP组在术后D7和D14术侧PWT显著升高(P<0.05)。(2)与Sham+Vehicle组相比,SNI+Vehicle组HO-1的表达在术后D7、D14明显增加(P<0.05),MOR、DOR无明显改变(P>0.05);与SNI+Vehicle组相比,SNI+COPP组的HO-1与MOR的表达在术后D7、D14有显著提高(P<0.05),DOR仍无明显改变(P>0.05)。结论:腹腔注射HO-1激动剂COPP可缓解大鼠神经病理性疼痛,调节阿片受体表达是其可能作用机制之一。
OBJECTIVE: To observe the changes of heme oxygenase-1 (HO-1) expression in the spinal cord of neuropathic pain (NP) rats and to investigate the effects of HO-1 protoporphyrin cobalt cobalt protoporphyrin Ⅸ, COPP) on neuropathic pain and its possible mechanism. Methods: We used a model of spared nerve injury (SNI). Male SD rats were randomly divided into three groups: Sham + Vehicle group, SNI + Vehicle and SNI + COPP group. From the first day after operation, Sham + Vehicle group and SNI + Vehicle group were injected intraperitoneally with 10 ml / kg DMSO and SNI + COPP group with 0.1% COPP 10 mg / kg intraperitoneally for 7 days. Rats in each group were respectively subjected to preoperative and postoperative 3 (D3), 7 (D7) and 14 (D14) days to determine the Paw withdrawl threshold (PWT) of 50%. The rats were sacrificed at D7 and D14 postoperatively, and the spinal cord on the L4-6 segment of the spinal cord was harvested. The expression of HO-1, μ-opioid receptor (MOR) and δ-opioid receptor , DOR) expression changes. Results: (1) There was no significant difference in PWT between preoperative and postoperative groups (P> 0.05). Compared with Sham + Vehicle group, postoperative PWI of SNI + Vehicle group and SNI + COPP group (P <0.05). Compared with SNI + Vehicle group, the PWT of Dl and D14 in SNI + COPP group was significantly higher than that in SNI + Vehicle group (P <0.05). (2) Compared with Sham + Vehicle group, the expression of HO-1 in SNI + Vehicle group increased significantly after D7 and D14 (P <0.05), but not in MOR and DOR (P> 0.05) The expression of HO-1 and MOR in SNI + COPP group was significantly increased at D7 and D14 (P <0.05), while DOR remained unchanged (P> 0.05). CONCLUSION: Intraperitoneal injection of HO-1 agonist COPP can relieve neuropathic pain in rats and regulate opioid receptor expression is one of its possible mechanisms.