【摘要】 目的 探讨吗啡对外周神经损伤性神经源性疼痛大鼠神经行为学及背根神经节中生长相关蛋白43(GAP-43)和神经生长因子(NGF)表达的影响。方法 选取成年SD大鼠65只,采用随机数字表法分成正常对照组(5只),坐骨神经慢性压迫性损伤(CCI)组(CCI组,20只),CCI后0.9%氯化钠注射液治疗对照组(NS组,20只),CCI后吗啡治疗组(M组,20只);CCI、NS和M组再按术后取材时间分为1、3、7、14 d 4个亚组(每亚组各5只大鼠)。手术仅损伤右侧坐骨神经,左侧作为正常对照。吗啡给药剂量为5 mg/kg腹腔注射。CCI、NS和M组大鼠分别于术后1、3、7、14 d测量机械缩足反射阈值(MWT)和热缩腿反射潜伏期(TWL),测量完毕后取术侧背根神经节,应用免疫组织化学方法 半定量检测背根神经节中GAP-43和NGF的表达。结果 CCI组、NS组、M组术后3、7、14 d MWT和TWL明显短于正常对照组[MWT:(7.3±1.2)、(7.2±0.9)、(12.6±1.6)g比(14.8±0.6)g;(5.9±0.7)、(5.8±0.6)、(7.9±0.8)g比(14.8±0.7)g;(4.3±0.4)、(4.5±0.7)、(5.4±0.6)g比(14.8±0.5)g;TWL:(1.07±0.05)、(1.05±0.06)、(1.31±0.16)s比(1.45±0.11)s;(0.97±0.05)、(0.96±0.05)、(1.10±0.12)s比(1.45±0.10)s;(0.86±0.04)、(0.88±0.07)、(1.01±0.06)s比(1.45±0.12)s,P<0.01],背根神经节中GAP-43和NGF的表达水平明显高于正常对照组[GAP43:(114.8±6.3)、(118.8±6.4)、(94.4±5.2)比(62.2±2.5);(118.0±4.3)、(122.4±5.5)、(89.7±3.0)比(62.2±2.5);(140.2±5.2)、(135.7±5.9)、(84.5±8.1)比(62.2±2.5);NGF:(134.0±3.8)、(131.5±3.6)、(98.3±3.6)比(71.6±3.4);(120.4±4.7)、(118.9±4.4)、(103.2±7.2)比(71.6±3.4);(117.9±4.1)、(116.5±5.9)、(95.4±3.6)比(71.6±3.4),P<0.01];M组与NS组和CCI组比较,术后3、7、14 d同时点的MWT和TWL均明显延长(P<0.01),GAP-43和NGF的表达均明显减少(P<0.01)。结论 腹腔注射吗啡能够明显减轻CCI后的热和机械性痛觉过敏,能有效抑制背根神经节中GAP43和NGF的高表达,说明吗啡对神经性疼痛治疗有效。更多还原

【Abstract】 Objective To explore the effect of morphine on the neurological behavior,the expression of growui associated protein-43(GAEM3) and nerve growth factor(NGF) in the dorsal root ganglion in neuropathic pain rat model induced by peripheral nerve chronic constriction injury.Methods Sixty-five SD rats were randomly divided into normal group(n =5),chronic constriction injury of the sciatic nerve(CCI) group(n=20),NS group(re =20,CCI + 0.9%sodium chloride) and M group(re =20,CCI + morphine).The rats in CCI,NS,M groups were divided equally into 4 subgroups according to the time points(1,3,7 and 14 days after surgery).In surgery,the right sciatic nerve was injured and the left side nerve was as a normal control.The morphine was given with a dosage of 5 mg/kg.The mechanical withdrawal threshold(MWT) and thermal withdrawal latency(TWL) of the rats in CCI,NS,M groups1,3,7 and 14 days after operation were measured;the dorsal root ganglions of injured sciatic nerves were harvested and immunohistochemistry was used to examine the expression of GAP-43 and NGF.Results Compared with those in normal group,die MWT and TWL in CCI,NS,M groups were significantly decreased 3 days[(7.3 ± 1.2),(7.2 ±0.9),(12.6 ±1.6) g vs(14.8+0.6) g;(1.07 ±0.05),(1.05 ±0.06),(1.31 ±0.16) s vs(1.45+0.11) s],7 days[(5.9+0.7),(5.8 ±0.6),(7.9 ±0.8) g vs(14.8 ±0.7) g;(0.97 ±0.05),(0.96 ±0.05),(1.10 +0.12) s vs(1.45+0.10) s]and 14 days after surgery[(4.3 ±0.4),(4.5 ±0.7),(5.4 ±0.6) g vs(14.8 ±0.5) g;(0.86±0.04),(0.88 ±0.07),(1.01 ±0.06) s vs(1.45 ±0.12) s](P<0.01).The expressions of GAP-43 and NGF in the dorsal root ganglion had a significant increase in CCI,NS,M groups compared with those in control group 3 days[(114.8 ±6.3),(118.8 ±6.4),(94.4 ±5.2) vs(62.2 ±2.5);(134.0 ±3.8),(131.5 ±3.6),(98.3 ±3.6) vs(71.6 ±3.4)],7 days[(118.0 ±4.3),(122.4 ±5.5),(89.7 ±3.0) vs(62.2 ±2.5);(120.4±4.7),(118.9±4.4),(103.2 ±7.2) vs(71.6 ±3.4)]and 14 days after surgery[(140.2 ±5.2),(135.7 +5.9),(84.5 ±8.1) vs(62.2±2.5);(117.9+4.1),(116.5 ±5.9),(95.4±3.6) vs(71.6±3.4)](P<0.01).Compared those in NS group,the MWT and TWL were significantly increased and the expressions of GAP-43 and NGF were significant declined in M group at the same time points(P <0.01).Conclusion Morphine can effectively relieve the symptom of heat and mechanical hyperalgesia after CCI,and it can also inhibit the high expression of GAP43 and NGF.更多还原