AMPK信号通路在异丙酚减轻老年大鼠短暂脑缺血再灌注损伤中的作用

目的探讨AMPK信号通路在异丙酚减轻老年大鼠短暂脑缺血再灌注损伤中的作用。方法健康雄性SD老龄大鼠(18²2月龄)150只,体重45022月龄)150只,体重450⁶00 g,采用随机数字表法将其分为5组(n=30):对照组(C组);假手术组(S组);缺血再灌注组(IR组);缺血再灌注组+异丙酚组(IR+P组)和缺血再灌注组+异丙酚组+AMPK激活剂组(IR+P+Y组)。采用Pusinelli四动脉阻断法建立全脑缺血模型。于缺血前10 min腹腔内注射异丙酚100 mg/kg,于夹闭动脉前时腹腔注射AMPK激活剂AICAR 500 mg/kg,假手术组仅暴露两侧翼孔和颈总动脉,对照组不行任何处理。采用Lawner等制定的评分标准神经行为学评估。于再灌注1、3和5 d时每组随机取10只处死,采用TUNEL法检测神经元的凋亡情况;采用Western blot法测定大鼠海马内AMPK、pAMPK、Bcl-2和Bax的表达。结果与C组比较,IR组、IR+P组和IR+P+Y组老年大鼠缺血/再灌注24 h后神经行为学评分升高,海马区TUNEL阳性神经元计数增加,海马AMPK、pAMPK表达水平升高,Bcl-2表达下调,Bax表达上调(P<0.05),与IR组比较,IR+P组老年大鼠缺血/再灌注24 h后神经行为学评分降低、海马区TUNEL阳性神经元计数减少、海马AMPK、pAMPK表达水平降低,Bcl-2表达上调、Bax表达下调(P<0.05),与IR+P组比较,IR+P+Y组老年大鼠缺血/再灌注24 h后神经行为学评分升高,海马区TUNEL阳性神经元计数增加,海马AMPK、p-AMPK表达水平升高,Bcl-2表达下调,Bax表达上调(P<0.05)。结论 AMPK信号通路参与了异丙酚减轻老年大鼠短暂脑缺血再灌注损伤的过程。

Role of AMPK singal pathway in propofol against transient cerebral ischemia/reperfusion injury of aged rats

Objective To evaluate the role of AMPK singal pathway in propofol against transient cerebral ischemia/reperfusion injury of aged rats. Methods One hundred fifty male Sprague-Dawley rats, weighing 450-600 g, were randomly divided into 5 groups （n=30）： control group （group C）, sham group （group S）, cerebral ischemia/reperfusion injury group （group IR）, cerebral ischemia/reperfusion injury group＋propofol（group IR＋P）, cerebral ischemia/reperfusion injury group＋propofol＋AICAR（group IR＋P＋Y）. Modified pusinelli 4-vessel-block was conduct for 3minutes to establish cerebral ischemia model. Propofol was infused by intraperitoneal injection at 100 mg/kg starting from 10 min before ischemia. AICAR was infused by intraperitoneal injection at 500 mg/kg before blocking artery. The NBS of all the rats were evaluated at the 24 h after reperfusion. At 1, 3 and 5 days after reperfusion, 10 rats from each group were sacrificed for Tunel staining and western blot analysis. AMPK, pAMPK, Bcl-2 and Bax expression were measured by western blot analysis. Results Compared with group C, the NBS, the number of apoptotic neurons and the amount of protein AMPK, pAMPK and Bax significantly increased, Bcl-2 significantly decreased in the group IR, group IR＋P and group IR＋P＋Y. Compared with group IR, the NBS, the number of apoptotic neurons and the amount of protein AMPK, pAMPK and Bax＆amp;nbsp;significantly decreased, Bcl-2 significantly increased in the group IR＋P. Compared with group IR＋P, the NBS, the number of apoptotic neurons and the expression of AMPK, pAMPK and Bax were significantly increased in the group IR＋P＋Y, but the expression of Bcl-2 was significantly decreased in the group IR＋P＋Y. Conclusion Activation of AMPK singal transduction pathway may be involved in the mechanism by which propofol reduces transient global cerebral ischemia-reperfusion in rats.