CAJ | 학술논문

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4,24 h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24 h血浆中促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)和皮质酮浓度. 结果野生型伤后4,24 h组脑含水量分别为(80.950±0.184)％、(82.178±0.255)％,基因敲除伤后4,24 h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(120.214±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,24 h为(189.613 ±4.802) ng/L;皮质酮浓度4h为(40.138±0.805) μg/L,24 h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,24 h为(124.93±11.001 7) ng/L;皮质酮浓度4h为(19.702±0.804) μg/L,24 h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-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.
목적 연구선감A2A수체재중도로뇌창상급성기수체-신상선축응격반응중적작용. 방법 장야생형、기인고제소서각18지안수궤수자표법분별분위정상대조조、상후4,24 h조,매조6지.사용선감A2A수체기인고제소서화야생형C57BL/6소서복제로뇌창상모형,ELISA법측정상후4h화24 h혈장중촉신상선피질격소(adrenocorticotropic hormone,ACTH)화피질동농도. 결과 야생형상후4,24 h조뇌함수량분별위(80.950±0.184)％、(82.178±0.255)％,기인고제상후4,24 h조뇌함수량분별위(80.006 ±0.199)％、(81.091±0.295)％,균고우각자대응적정상대조조(P＜0.01),차야생형손상조뇌함수량고우기인고제손상조(P＜0.01).기인고제정상대조조혈장ACTH농도위(120.214±2.472) ng/L,피질동농도위(27.814 ±0.888) μg/L,균고우야생형정상대조조(91.767±7.395) ng/L화(11.430±0.644)μg/L(P ＜0.01).기인고제손상조혈장ACTH농도4h위(174.776±5.040) ng/L,24 h위(189.613 ±4.802) ng/L;피질동농도4h위(40.138±0.805) μg/L,24 h위(37.440±0.485) μg/L.야생형손상조혈장ACTH농도4h위(119.594±6.945) ng/L,24 h위(124.93±11.001 7) ng/L;피질동농도4h위(19.702±0.804) μg/L,24 h위(17.602±0.743) μg/L,기인고제손상조증고폭도현저고우야생형손상조(P＜0.05).결론 고제선감A2A수체재중도로뇌창상급성기가증가ACTH화피질동석방,대수체-신상선축응격반응유촉진작용,위고제A2A수체발휘신경보호작용제공료신적해석.
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 siμ 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] 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 ＜0.0l].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 craniocerebral trauma and promotes pituitary-adrenal stress response.This may provide a novel explanation for the neuroprotective effect of A2A receptor deficiency.