小鼠颅脑创伤急性期腺苷A2A受体对垂体-肾上腺轴应激反应的影响

Effect of adenosine A2A receptor on stress response of pituitary-adrenal axis in acute phase of craniocerebral trauma in mice

目的研究腺苷A2A受体在中度颅脑创伤急性期垂体-肾上腺轴应激反应中的作用。方法将野生型、基因敲除小鼠各18只按随机数字表法分别分为正常对照组、伤后4，24h组，每组6只。使用腺苷A2A受体基因敲除小鼠和野生型C57BL／6小鼠复制颅脑创伤模型，ELISA法测定伤后4h和24h血浆中促肾上腺皮质激素（adrenoeorticotropichormone，ACTH）和皮质酮浓度。结果野生型伤后4，24h组脑含水量分别为（80．950±0．184）％、（82．178±0．255）％，基因敲除伤后4，24h组脑含水量分别为（80．006±0．199）％、（81．091±0．295）％，均高于各自对应的正常对照组（P〈0．01），且野生型损伤组脑含水量高于基因敲除损伤组（P〈0．01）。基因敲除正常对照组血浆ACTH浓度为（120．2144-2．472）ng／L，皮质酮浓度为（27．814±0．888）μg/L，均高于野生型正常对照组（91．767±7．395）ng／L和（11．430±0．644）μg/L（P〈0．01）。基因敲除损伤组血浆ACTH浓度4h为（174．776±5．040）ng／L，24h为（189．613±4．802）ng／L；皮质酮浓度4h为（40．138±0．805）μg/L，24h为（37．440±0．485）μg/L。野生型损伤组血浆ACTH浓度4h为（119．594±6．945）ng／L，24h为（124．93±11．0017）ng／L；皮质酮浓度4h为（19．702±0．804）μg/L，24h为（17．602±0．743）μg/L，基因敲除损伤组增高幅度显著高于野生型损伤组（P〈0．05）。结论敲除腺苷A2A受体在中度颅脑创伤急性期可增加ACTH和皮质酮释放，对垂体一肾上腺轴应激反应有促进作用，为敲除A2A受体发挥神经保护作用提供了新的解释。

Objective To investigate the effect of adenosine A2A receptor on pituitary-adrenal axis response in acute phase of moderate craniocerebral trauma. Methods Eighteen adenosine A2A receptor knock-out mice in a C57BL/6 background and another eighteen their wild-type littermates were divided into normal control group and craniocerebral trauma for 4 hours group, and craniocerebral trauma for 24 hours group according to random number table, with six mice per group. Plasma levels of adrenocorticotropic-hormone （ACTH） and corticosterone at hours 4 and 24 postinjury were determined using ELISA method. Results At 4 and 24 hours, brain water content in wild-type mice [ （ 80. 950 ± 0. 184） % , （82. 178 ±0. 255 ）% respectively l was higher than that in gene knock-out mice [ （80-006± 0. 199）%, （ 81. 091 ± 0.295 ） % respectively, P 〈 0.01 ]. Besides, brain water content in both wild-type and gene knock-out mice increased after injury （P 〈 0.01 ）. Plasma levels of ACTH and corticosterone were higher in geneknock-out sham mice than in wild-type sham mice [ （ 120. 214 ±2. 472 ） ng/L vs （ 91. 767± 7. 395 ） ng/L, （27. 814±0. 888 ）μg/L vs （ 11. 430 ±0. 644） μg/L respectively, P 〈 0.01 ]. At 4 and 24 hours, plasma levels of ACTH [ （ 174. 776±5. 040） ng/L, （ 189. 613±4. 802） ng/L respectively] in geneknock-out mice showed a higher increase than those in wild-type mice [ （ 119. 594 ± 6. 945 ） ng/L, （ 124.93 ± 11. 001 7 ） ng/L respectively, P 〈 0.05 ]. Moreover, plasma levels of corticosterone [ （40. 138 ＋ 0. 805 ）μg/L] at 4 hours and [ （37. 440 ± 0. 485 ）μg/L] at 24 hours in gene knock-out mice showed a same result as compared with that in wild-type mice [ （ 19.702 -＋0.804） μg/L, （ 17. 602 ±0.743） μg,/L respectively, P 〈 0.05]. Conclusions Knock-out of adenosine A2A receptor increases the release of ACTH and corticosterone in acute stage of moderate cranioeerebral trauma and promotes pituitary-adrenal stress response. This may provide a novel explanation for the neuroproteetive effect of A2A receptor deftclency.