学术论文

      右美托咪定对大鼠肠缺血再灌注致胃粘膜损伤的影响

      Effect of dexmedetomidine on gastric mucosal injury induced by intestinal ischemia-reperfusion in rats

      摘要:
      目的 评价右美托咪定对大鼠肠缺血再灌注致胃粘膜损伤的影响.方法 健康雄性SD大鼠36只,体重200~250 g,4~5月龄,采用随机数字表法,将其分为4组(n=9):假手术组(S组)、肠缺血再灌注组(I/R组)、低剂量右美托咪定组(LD组)和高剂量右美托眯定组(HD组).LD组和HD组缺血前1h开始分别经尾静脉输注右美托咪定2.5、5.0 μg·kg-1·h-1,持续1h,采用夹闭肠系膜上动脉1h再灌注2h的方法制备大鼠肠缺血再灌注损伤模型.再灌注2h时处死大鼠,取胃组织,光镜下观察胃粘膜病理学结果;检测胃粘膜丝氨酸/苏氨酸蛋白激酶(Akt)、磷酸化Akt(p-Akt)、活化的caspase-3和caspase-3的表达,并计算p-Akt与Akt表达的比值反映Akt磷酸化水平,计算活化的caspase-3与caspase-3表达的比值反映caspase-3激活水平.结果 与S组比较,I/R组胃粘膜Akt表达上调,胃粘膜p-Akt表达下调,胃粘膜Akt磷酸化水平降低,胃粘膜caspase-3激活水平升高,LD组和HD组胃粘膜p-Akt表达上调,胃粘膜Akt磷酸化水平和caspase-3激活水平升高(P<0.05);与I/R组比较,LD组和HD组胃粘膜Akt表达下调,胃粘膜p-Akt表达上调,胃粘膜Akt磷酸化水平升高,胃粘膜caspase-3激活水平降低(P<0.05);LD组和HD组间上述指标比较差异无统计学意义(P>0.05).LD组和HD组胃粘膜损伤程度明显轻于I/R组,LD组和HD组胃粘膜损伤程度无明显差异.结论 右美托咪定可减轻大鼠肠缺血再灌注致胃粘膜损伤,其机制可能与激活PI3K/Akt信号通路从而抑制细胞凋亡有关.
      Abstract:
      Objective To evaluate the effect of dexmedetomidine on gastric mucosal injury induced by intestinal ischemia-reperfusion (I/R) in rats.Methods Thirty-six healthy male Sprague-Dawley rats,aged 4-5 months,weighing 200-250 g,were randomly divided into 4 groups (n =9 each) using a random number table:sham operation group (group S),intestinal I/R group (group I/R),low-dose dexmedetomidine group (group LD),and high-dose dexmedetomidine group (group HD).Intestinal I/R was produced by occlusion of the superior mesenteric artery for 1 h followed by 2 h reperfusion in anesthetized rats.Dexmedetomidine 2.5 and 5.0 μg · kg-1 · h-1 were infused via the caudal vein for 1 h starting from 1 h before ischemia in LD and HD groups,respectively.The rats were sacrificed at 2 h of reperfusion,and the gastric mucosa was obtained for examination of the pathological changes (with light microscope) and for determination of the expression of serine/threonine kinase (Akt),phosphorylated Akt (p-Akt),activated caspase-3 and caspase-3 (by Western blot).The ratio of p-Akt to Akt (p-Akt/Akt)was calculated to reflect the phosphorylation of Akt.The ratio of activated caspase-3 to easpase-3 (activated caspase-3/caspase-3) was calculated to reflect the activation of caspase-3.Results Compared with group S,the expression of Akt was significantly up-regulated,the expression of p-Akt was significantly downregulated,the phosphorylation of Akt was significantly decreased,and the activation of caspase-3 was significantly increased in group I/R,and the expression of p-Akt was significantly up-regulated,and the phosphorylation of Akt and activation of caspase-3 were significantly increased in LD and HD groups (P<0.05).Compared with group I/R,the expression of Akt was significantly down-regulated,the expression of p-Akt was significantly up-regulated,the phosphorylation of Akt was significantly increased,and the activation of caspase-3 was significantly decreased in LD and HD groups (P<0.05).The degree of gastric mucosal injury was significantly lower in LD and HD groups than in group I/R,and there was no significant difference in the degree of gastric mucosal injury between group LD and group HD.Conclusion Dexmedetomidine can attenuate gastric mucosal injury induced by intestinal I/R,and the mechanism may be related to activation of PI3K/Akt signaling pathways and inhibition of cell apoptosis in rats.
      Author: Yue Fang Wu Yawen Wang Haijin Ding Ruiwen Liang Shaoling Li Bulong Chen Youquan
      作者单位: 510150,广州医科大学附属第三医院麻醉科
      刊 名: 中华麻醉学杂志 ISTICPKU
      年,卷(期): 2016, 36(3)
      在线出版日期: 2016年7月27日
      基金项目: Guangzhou Education Scientific Planning Subject,Guangzhou Science Technology and Innovation Commission—Popularization of Science Specific Project in 2015 (201507020064)广州市教育科学规划课题,广州市科技创新委员会—2015年科普专项项目