慢性坐骨神经损伤大鼠中脑导水管周围灰质MC4R的表达及HS014对热痛觉过敏的影响

发布时间：2018-06-02 00:24

本文选题：慢性坐骨神经损伤 + 中脑导水管周围灰质　；参考：《现代中西医结合杂志》2016年35期

【摘要】：目的观察大鼠慢性坐骨神经损伤(CCI)后不同时间点中脑导水管周围灰质(PAG)4型黑皮质素受体(MC4R)mRNA表达变化及给予选择性MC4R拮抗剂HS014对CCI大鼠疼痛行为学的影响。方法 1将42只健康成年雄性Wistar大鼠随机分为对照组6只、假手术组18只和CCI组18只,检测各组大鼠术前和术后3,7,14 d热缩足潜伏期(TWL),假手术组和CCI组分别于术后3,7,14 d,对照组于术后14 d TWL检测完成后处死大鼠,取PAG脑组织,用半定量RT-PCR法检测PAG脑区MC4R mRNA表达情况。2将30只健康成年雄性Wistar大鼠随机分为对照组6只、假手术组6只和CCI组18只,均先进行PAG置管。置管后7 d,CCI组随机分成CCI+NS组、CCI+HS014 5μg组和CCI+HS014 10μg组,每组6只。假手术组和CCI各组手术造模。术后7 d,CCI+NS组经导管注射生理盐水0.5μL,CCI+HS014 5μg组注射HS014 5μg/0.5μL,CCI+HS014 10μg组注射HS014 10μg/0.5μL。检测各组大鼠置管后7 d、术后7 d和干预后(注射后10~30 min完成检测)TWL。结果 CCI组大鼠术后3 d开始出现TWL缩短(P0.05),术后7 d和14 d TWL缩短更加明显(P均0.05),与对照组和假手术组比较差异均有统计学意义(P均0.05)。CCI组术后各时间点MC4RmRNA表达量均明显高于对照组和假手术组(P均0.05),并且随着CCI术后时间的推移,MC4RmRNA的表达量逐渐增高(P均0.05)。CCI各组大鼠术后7 d TWL明显低于置管后7 d(P均0.05);CCI+NS组干预后TWL与术后7 d比较差异无统计学意义(P0.05),而CCI+HS014 5μg组和CCI+HS014 10μg组干预后TWL均明显长于术后7 d和CCI+NS组(P均0.05),CCI+HS014 10μg组干预后TWL明显长于CCI+HS014 5μg组(P0.05)。结论 CCI可引起PAG中MC4RmRNA的表达增加,其选择性拮抗剂HS014可剂量依赖性减轻CCI大鼠的热痛觉过敏,提示PAG中MC4R的表达增加可能参与神经病理性疼痛的形成和维持。
[Abstract]:Objective to observe the changes of MC4RN mRNA expression in periaqueductal gray matter of rats with chronic sciatic nerve injury (CCI) at different time points and the effect of selective MC4R antagonist HS014 on the pain behavior of CCI rats. Methods 1 Forty-two healthy adult male Wistar rats were randomly divided into control group (n = 6), sham operation group (n = 18) and CCI group (n = 18). Rats in each group were examined for the latent period of thermal contraction of foot at 714 days before and 3 days after operation. The rats in sham operation group and CCI group were killed on the 14th day after operation, and the rats in the control group were killed after TWL detection on the 14th day after operation. The brain tissues of PAG were taken out. The expression of MC4R mRNA in PAG brain was detected by semi-quantitative RT-PCR. 2 30 healthy adult male Wistar rats were randomly divided into control group (n = 6), sham operation group (n = 6) and CCI group (n = 18). Seven days after catheterization, CCI group was randomly divided into CCI NS group (CCI 5 渭 g) and CCI HS014 10 渭 g group (6 rats in each group). Sham operation group and CCI group were operated to model. 7 days after operation, normal saline 0.5 渭 L and HS014 5 渭 g / 0.5 渭 L HS014 5 渭 g / 0.5 渭 L CCI HS014 10 渭 g / 10 渭 g / HS014 were injected into CCI NS group 7 days after operation. TWL was detected 7 days after catheterization, 7 days after operation and after intervention (1030 min after injection). Results in the CCI group, TWL shortening began to appear 3 days after operation (P 0.05), and TWL shortening on the 7th and 14th days after operation was more obvious (P 0.05). There was significant difference between the control group and the sham operation group in the expression of MC4RmRNA at different time points in the 0.05).CCI group. The expression of MC4R mRNA in 0.05).CCI group was significantly higher than that in control group and sham operation group (P 0.05). The expression of MC4R mRNA in 0.05).CCI group was significantly lower than that in control group and sham operation group on the 7th day after operation. The TWL was significantly lower in 0.05).CCI group than that in control group and sham operation group at 7 days after intervention and 7 days after operation. The expression of MC4R mRNA in 0.05).CCI group was significantly lower than that in control group and sham operation group. There was no significant difference in TWL between CCI HS014 5 渭 g group and CCI HS014 10 渭 g group (P 0.05), but the TWL of CCI HS014 5 渭 g group and CCI HS014 10 渭 g group was significantly longer than that of CCI HS014 5 渭 g group and CCI NS group (P 0.05). Conclusion CCI can increase the expression of MC4RmRNA in PAG, and its selective antagonist HS014 can attenuate the hyperthermia in CCI rats in a dose-dependent manner, suggesting that the increased expression of MC4R in PAG may be involved in the formation and maintenance of neuropathic pain.
【作者单位】：内蒙古医科大学附属医院;青岛大学医学院附属医院;
【分类号】：R745.4

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