应用ERKO小鼠观察雌激素对痛觉的影响及ERs的作用特点  

Using ERKO mice for study pain modulation by estrogen via ERs

作　　者：丁海霞 王强 王宇[2] 王军[2] 刘景丽[2] 董海蓉[3] 肖杭 

机构地区：[1]南京医科大学第一附属医院老年神经内科,江苏南京210029 [2]南京医科大学公共卫生学院神经毒理研究室,江苏南京210029 [3]南京医科大学第一附属医院神经内科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2011年第12期1731-1736,共6页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金(81072329);中国博士后基金(20110491450);江苏省博士后基金(1101027c);江苏省高校自然科学基金(09KJB310005);江苏省普通高校研究生科研创新计划项目(CX10B_348Z);江苏省六大人才高峰(2009026)

摘　　要：目的:探讨雌激素通过ERs对痛觉的影响。方法:WT、αERKO和βERKO小鼠随机分为去卵巢加17β-E2组(OVX+17β-E2)和去卵巢组(OVX+Oil),甩尾热痛仪和热痛刺激仪测痛,并应用福尔马林致痛模型评价雌激素对痛觉的影响。结果:将WT小鼠卵巢切除后给予外源性雌激素,发现17β-雌二醇(17β-E2)对甩尾痛阈和缩足痛阈没有影响,敲除ERα或ERβ后甩尾痛阈和缩足痛阈也没有变化;17β-E2能够降低福尔马林炎症性痛实验的Ⅱ相反应,但对Ⅰ相反应无影响。进一步应用ERKO小鼠模型观察ERα和ERβ的作用特点发现,较WT小鼠,βERKO雌性小鼠在福尔马林炎症性痛模型Ⅱ相疼痛反应行为的时间减少,而在Ⅰ相反应中没有差别;αERKO小鼠福尔马林炎症性痛实验与WT比较没有明显差异。结论:雌激素可以影响慢性炎性痛,可能与影响急性痛进程无关。ERβ亚型在雌激素调节痛觉传递和调制过程中发挥着重要作用。Objective：To verify the involvement of ERα and ERβ on acute and persistent pain modulation by estradiol.Methods：The involvement of both receptors on nociceptive responses was measured by tail-flick,hotplate and formalin tests in αERKO and βERKO female mice.Ovariectomies followed by estrogen replacement were performed in the groups to insure comparable sex hormone levels.Results：WT mice given E2 showed no changes in tail-flick latency and hot plate latency.There were also no significant differences between WT and αERKO or βERKO mice.Estradiol significantly reduced the overall number of flinches in PhaseⅡ（not phase Ⅰ） during the formalin nociceptive response.Using ERKO mice,we found that βERKO（not αERKO） female mice showed lower nociceptive responses compared to WT female mice in the phase Ⅱ（not phase Ⅰ） in the formalin test,but suggesting that the pain was modulated by ERβ.Conclusion：Estrogen specifically influences nociceptive responses,and ERβ plays an important role in endogenous pain modulation systems.

关 键 词：雌激素受体 基因敲除小鼠 痛觉 

分 类 号：R329.26[医药卫生—人体解剖和组织胚胎学]