黄体酮对大鼠外伤性脑损伤后脑水肿及周围组织细胞凋亡和神经功能的影响

Effects of progesterone on brain edema and peripheral tissue apoptosis and neurological function in rats after traumatic brain injury

目的探究黄体酮对大鼠外伤性脑损伤后脑水肿及周围组织细胞凋亡和神经功能的影响。方法雄性Wistar成年大鼠随机分为假手术组(Sham组;开右侧顶部骨窗而无脑损伤)、脑损伤组(TBI组;开右侧顶部骨窗,且参照Freeney自由落体撞击致伤方法建造重型颅脑损伤模型)、脑损伤后接受黄体酮治疗组(P-TBI组;建立脑损伤模型后腹腔注射0.8 ml/kg黄体酮)、脑损伤后注射二甲基亚砜(DMSO)组(D-TBI组;建立脑损伤模型后腹腔注射0.8 ml/kg DMSO),每组24只,再将其分为损伤后1 d、3 d、5 d、7 d组,各6只。比较各组大鼠不同时间点环氧化物水解酶-2(COX-2)表达量,脑组织含水量、Bcl-2及Bax蛋白阳性细胞数及神经细胞凋亡情况。利用m NSS量表评价各组大鼠损伤后不同时间的神经功能。结果随着损伤时间延长,Sham组大鼠脑组织COX-2表达水平、脑组织含水量、神经细胞凋亡百分比及m NSS评分无明显变化(P>0.05)。TBI组大鼠随着损伤时间延长其脑组织COX-2表达水平、脑组织含水量、神经细胞凋亡百分比及m NSS评分均降低(P<0.05),且各时间点均高于Sham组(P<0.05)。D-TBI组及P-TBI组大鼠随着损伤时间延长其脑组织COX-2表达水平、脑组织含水量、神经细胞凋亡百分比及m NSS评分均降低(P<0.05),且P-TBI组高于TBI组(P<0.05)。损伤后7 d,TBI组大鼠脑组织Bcl-2、Bax阳性细胞数均高于Sham组(P<0.05);且P-TBI组大鼠脑组织Bcl-2阳性细胞数高于TBI组,Bax阳性细胞数低于TBI组(P<0.05)。结论黄体酮能有效缓解大鼠外伤性脑损伤后脑水肿情况、抑制周围组织细胞凋亡,对其神经功能有一定保护作用。

Objective To explore the effects of progesterone on brain edema and peripheral tissue apoptosis and neurological function in rats after traumatic brain injury.Methods Male Wistar adult rats were randomly divided into sham operation group(Sham group,open right top bone window without brain injury),traumatic brain injury group(TBI group,open the right top bone window,and build a severe head injury model by referring to Freeney’s free fall impact injury method),progesterone treatment after brain injury group(P-TBI group,establish a brain injury model after intraperitoneal injection of 0.8 ml/kg progesterone)and dimethyl sulfoxide(DMSO)after brain injury group(D-TBI group,establish a brain injury model after intraperitoneal injection of 0.8 ml/kg DMSO),with 24 rats in each group.And then the groups were divided into 1 d,3 d,5 d,7 d after injury group,with 6 rats in each group.The traumatic brain injury model was established by Freeney method.The expressions of epoxide hydrolase-2(COX-2),brain water content,positive cells quantities of Bcl-2 and Bax protein and nerve cells apoptosis were compared among groups at different time points.The neurological function of each group at different time points after injury was evaluated by m NSS scale.Results With the extension of injury time,the expression of COX-2,brain water content,percentage of neuronal apoptosis and m NSS score in the brain tissue of the Sham group had no significant changes(P>0.05).The COX-2 expression level,brain tissue water content,neural cell apoptosis percentage,and m NSS scores of rats in TBI group decreased as the injury time prolonged(P<0.05),and all time points were higher than those in Sham group(P<0.05).In the D-TBI group and the P-TBI group,the expression of COX-2 in brain tissue,brain tissue water content,percentage of neuronal apoptosis,and m NSS scores decreased as the injury time increased(P<0.05),and P-TBI Group was higher than TBI group(P<0.05).Seven days after the injury,the number of Bcl-2 and Bax positive cells in the brain tissue of the TBI group was higher than that in the Sham group(P<0.05);and the number of Bcl-2 positive cells in the brain tissue of the P-TBI group was higher than that in the TBI group.Bax The number of positive cells was lower than that in TBI group(P<0.05).Conclusion Progesterone can effectively alleviate brain edema after traumatic brain injury in rats,and inhibit the peripheral tissue apoptosis,and it has a certain protective effect on its neurological function.