右美托咪啶对脓毒症大鼠肠黏膜上皮细胞凋亡的影响

Effect of Dexmedetomidine on apoptosis of intestinal mucosalepithelial cells in septic rats

目的评价右美托咪啶对脓毒症大鼠肠黏膜细胞凋亡的影响。方法清洁级Wistar雄性大鼠60只,体重240~270 g,8周龄,采用随机数字法分为3组(20例):假手术组(Sham组)、模型组(M组)、右美托咪啶组(D组)。除Sham组外,余组均采用盲肠结扎穿孔法(CLP)建立脓毒症大鼠模型,Sham组仅开腹暴露盲肠,不结扎,关腹。术后24h取血检测各组大鼠血清肿瘤坏死因子(TNF)-α浓度、白细胞介素(IL)-6浓度;取血后处死全部大鼠取回肠组织,采用免疫组织化学法检测肠组织Bax和Bcl-2的表达,计算Bcl-2/Bax比值;采用末端脱氧核苷酸转移酶介导的duTP缺口末端标记测定法(TUNEL)法确定凋亡指数(AI)。结果与Sham组比较,M组、D组血清TNF-α、IL-6浓度和AI升高,肠组织Bax和Bcl-2表达上调,Bcl-2/Bax比值降低(P<0.05);与M组比较,D组血清TNF-α、IL-6浓度和AI降低,肠组织Bax和Bcl-2表达下调,Bcl-2表达上调,Bcl-2/Bax比值升高(P<0.05)。结论右美托咪啶减轻脓毒症大鼠肠黏膜上皮细胞损伤,与抑制细胞凋亡有关。

Objective To evaluate the effect of Dexmedetomidine on the apoptosis of mucosal epithelial cells in septic rats.Methods Sixty Wistar male rats,weighing 240-270 g and aged 8 weeks old,were randomly divided into 3 groups(n=20 each):Sham operation group(Sham group),model group(M group)and Dexmedetomidine group(D group).Except for the Sham group,septic rat models were established by cecal ligation and perforation(CLP)in the other groups.Laparotomy was performed alone to expose cecum in the Sham group without ligation,then the abdominal closure was performed.The serum levels of TNF-αand IL-6 in each group were measured at 24 h after operation.After blood collection,all rats were sacrificed and ileum tissues were taken.The expression levels of Bax and Bcl-2 in intestinal tissues were examined by immunohistochemical method,and the ratio of Bcl-2/Bax was calculated.Apoptosis index(AI)was determined by the terminal dexynucleotidyl transferase(TdR)-mediated duTP nick end labeling(TUNEL)assay.Results Compared with the Sham group,the serum levels of TNF-αand IL-6 and AI increased in M group and D group,the expressions levels of Bax and Bcl-2 were up-regulated in intestinal tissues,and the BCL-2/Bax ratio decreased(all P<0.05).Compared with M group,the serum levels of TNF-αand IL-6 and AI decreased in D group,the expressions levels of Bax and Bcl-2 were down-regulated in intestinal tissues,and the BCL-2/Bax ratio elevated(all P<0.05).Conclusion The reduction intestinal mucosal epithelial cell injury by Dexmedetomidine in septic rats may relate to the inhibition of cell apoptosis.