【摘要】 目的观察孕酮对大脑中动脉栓塞(MCAO)大鼠脑组织TASK3蛋白表达的影响,探讨孕酮对脑缺血再灌注损伤大鼠的脑保护作用及机制。方法雄性SD大鼠随机分为正常对照组、假手术组、缺血再灌注组(I/R组)和孕酮+I/R组,后3组按缺血再灌注后不同时间随机分为0 h、6 h、12 h、24 h、48 h、72 h、96 h和120 h 8个亚组。线栓法建立大鼠右侧MCAO模型,缺血2 h再灌注24 h进行脑损伤评估,检测各组大鼠死亡率、神经功能缺陷评分以及2,3,5-氯化三苯基四氮唑(TTC)染色测定脑梗死体积;采用免疫印迹法检测各组大鼠脑组织缺血2 h再灌注后不同时间点TASK3蛋白的表达。结果孕酮+I/R组大鼠死亡率(18.18%)明显低于I/R组(40.66%),该组动物脑梗死体积(21.85%±3.53%)也显著低于I/R组(37.21%±3.50%)(P<0.01),且该组神经功能缺陷评分(2.00±0.74)显著低于I/R组(2.67±0.49)(P<0.05)。与正常对照组相比,假手术组各时间点脑组织TASK3蛋白的表达无明显变化,而I/R组各时间点脑组织TASK3蛋白的表达均显著降低(P<0.05);与I/R组相比,孕酮+I/R组各时间点脑组织TASK3蛋白的表达显著升高(P<0.05)。结论孕酮对脑缺血再灌注损伤的大鼠具有脑保护作用,其机制可能与上调TASK3通道蛋白的表达有关。更多还原

【Abstract】 Objective To investigate the effect of progesterone( PROG) on the expression of Two-pore domain K channel3( TASK3) after cerebral ischemia-reperfusion injury in rats. Methods Male Sprague-Dawley rats were divided into four groups randomly: normal control group,sham-operated group,ischemia-reperfusion group( I / R group) and PROG + I / R group. Sham-operated group,I / R group and PROG + I / R group were divided into 0 h、6 h、12 h、24 h、48 h、72 h、96 h and120 h eight subtypes according to different reperfusion time. The model of MCAO was established by the line-embolism method. The mortality rate,the nervous functional defect degree and the volumes of cerebral infarction were evaluated when rats were suffered 2 h /24 h ischemia-reperfusion stress. The expression of TASK3 protein in right brain was measured by Western blotting assay at reperfusion time of 0 h、6 h、12 h、24 h、48 h、72 h、96 h and 120 h after 2 h ischemia. Results The mortality rate in PROG + I / R rats( 18. 18%) were obviously lower than that of I / R group( 40. 66%). The nervous defect scores in PROG + I / R rats( 2. 00 ± 0. 74) were significant lower than that of I / R group( 2. 67 ± 0. 49)( P <0. 05). The volumes of cerebral infarction in PROG + I / R group( 21. 85% ± 3. 53%) were significant lower than that of I /R group( 37. 21% ± 3. 50%)( P < 0. 01). No significant difference of the protein expression of TASK3 in brain tissues at all time points between normal control group and sham-operated group was detected. However,the protein expression of TASK3 in brain tissue at all time points significant decreased in I / R group as compared with normal control group( P <0. 05). Compared with I / R group,the protein expression of TASK3 in brain tissue at all time points dramatically increased in PROG + I / R group( P < 0. 05). Conclusion Progesterone exerts the neuroprotective effect on focal cerebral ischemia /reperfusion injury in rats,the protective mechanism might be associated with up-regulating the expression of TASK3 protein in brain.更多还原