黑皮质素4受体介导神经病理性疼痛机制的研究

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1、青岛大学硕士学位论文黑皮质素4受体介导神经病理性疼痛机制的研究姓名：夏江玲申请学位级别：硕士专业：麻醉学指导教师：褚海辰20120602摘要目的：观察黑皮质素4受体(MC4R)拮抗剂对背根神经节(DRG)和脊髓背角p38MAPK的影响，探讨MC4R和p38MAPK之间的关系。方法：鞘内置管成功后，采用坐骨神经结扎(CCI)模型，将成熟雄性SD大鼠96只分为四组，假手术组，只暴露坐骨神经不予结扎，CCI组，单纯结扎坐骨神经，H组，CCI后鞘内注射黑皮质素受体4拮抗剂HS014，5¨∥天，持续7天。S组，鞘内注射p38MAPK抑制

2、剂SB203580，10m∥天，持续7天。于术后3天、7天、14天观察大鼠的热痛阈，免疫组化和ELISA及Western检测L4．6背根神经节和脊髓背角MC4R和磷酸化的p38MAPK(p—p38MAPK)变化。结果：CCI组较假手术组术后各时间点热痛阈显著下降(p

3、无明显变化而p-p38MAPK显著下降(p

4、reasetheneuropathicpaininducedbychromcconstrict蜘uD，(ccD．Methods：MaleWistarratsweighing280-3209wereusedinthisstudy，Theneuropathicpainmodelwasestablishedbychronicconstrictinjury(cci)tosciaticnerve．AfteralltheratsweTesuccessfullyintrathecallycatheterizedandassignedtoCC

5、Iorshamsurgery．Andtheywererandomlydividedintofourgroups，shamgroup，onlyexposethesciaticnervewithomsurgicalligation；CCIgroup，sciaticnervewereexposedand4looseligatureswereplacedonthesciaticnerveat1Himintervals、以th禾0silksuture；Hgroup，CCI+HS014(MC4Rantagonist)，5ug／day,fo

6、rS吖erldays；SGroup，CCI+SB203580(p38MAPKinhibitor)10rag／day，forseveildays．ThermalThresholdWasmeasuredbeforeoperationandonthe3rd，7thand14thdayafterCCI．ThelevelofMC4Randphosphorylatedp38MAPK(p-p38MAPK)indorsalrootganglionandlumbarspinalcordwastestedbyimmunohistochemistr

7、yandp-p38MAPKwerealsotestedbyELISA(enzyme-linkedimmunosorbantassay)andwesternblotResults：Thethermalthr懿holdWaSsignificantlylowerinCCIgroupthaninshamoperationgroup(P<0．O1)，andMC4Randp-p38MAPKexpressionintheDI好andspinalcordwel"esignificantlyincreasedinCCIgroup倦shamgro

8、up(p