右美托咪定对严重烫伤大鼠心肌细胞凋亡的影响

Effect of dexmedetomidine on apoptosis in myocardial cells in rats with severe scald

目的 评价右美托咪定对严重烫伤大鼠心肌细胞凋亡的影响.方法 健康成年雄性SD大鼠18只,体重220 ～ 280 g,采用随机数字表法,将其分为3组（n=6）：对照组（C组）、烫伤组（B组）、烫伤＋右美托咪定30 μg/kg组（D组）.建立大鼠30％体表面积烫伤模型,致伤后按Parkland公式补液抗休克治疗.D组伤后即刻腹腔注射右美托咪定30 μg/kg,B组腹腔注射等容量生理盐水.于烫伤后12h取左心室心肌组织,光学显微镜观察心肌组织病理学结果,应用TUNEL法确定心肌细胞凋亡指数,应用Western blot法检测心肌葡萄糖调节蛋白78 （GRP78）、C/EBP同源蛋白（CHOP）表达.结果 与C组比较,B组和D组心肌细胞凋亡指数升高、心肌GRP78及CHOP表达上调（P＜0.05）;与B组比较,D组心肌细胞凋亡指数降低、心肌GRP78与CHOP表达下调（P＜0.05）.B组心肌病理学损伤明显,D组心肌病理学损伤明显减轻.结论 右美托咪定可通过抑制严重烫伤大鼠内质网应激介导的心肌细胞凋亡,发挥心肌保护作用.

Objective To evaluate the effect of dexmedetomidine on apoptosis in myocardial cells in rats with severe scald.Methods Eighteen healthy male Sprague-Dawley rats,weighing 220-280 g,were randomly divided into 3 groups （n =6 each） using a random number table：control group （group C）,scald group （group B）and scald ＋ dexmedetomidine 30 μg/kg group （group D）.Thirty percent of the total body surface was shaved and then exposed to 94 ℃ water for 12 s.Rats were resuscitated with isotonic saline according to Parkland formula immediately after burn.Sham burn was produced in C group.In group D,the rats received inraperitoneal injection of dexmedetomidine 30 μg/kg immediately after burn,and the equal volume of normal saline was injected in group B.The left ventricle was removed at 12 h after burn to observe the pathological changes of myocardial tissues with light microscope and to detect the apoptosis in myocardial cells （TUNEL assay） and expression of glucose-regulated protein 78 （GRP78） and C/EBP-homologous protein （CHOP） （using Western blot）.The apoptosis index was calculated.Results Compared with group C,the apoptosis index was significantly increased and the expression of GRP78 and CHOP was up-regulated in B and D groups （P ＜ 0.05）.Compared with group B,the apoptosis index was significantly decreased and the expression of GRP78 and CHOP was down-regulated in group D （P ＜ 0.05）.The pathological changes were obvious in group B and were significantly attenuated in group D.Conclusion Dexmedetomidine can protect myocardium through inhibiting endoplasmic reticulum stress-mediated apoptosis in myocardial cells in rats with severe scald.