丙戊酸钠对重度烧伤大鼠心脏和脑组织保护作用的量效关系研究  

The study of dose-effect relationship of valproic acid on protecting heart and brain in a rodent model of severe burn injury

作　　者：王晓青[1] 罗红敏[2] 刘皈阳[1] 马建丽[1] 贾燕花[1] 胡森[2] 

机构地区：[1]解放军总医院第一附属医院药剂药理科,北京100048 [2]解放军总医院第一附属医院创伤外科研究室,北京100048

出　　处：《感染．炎症．修复》2014年第1期27-30,共4页Infection Inflammation Repair

基　　金：全军"十一五"基金资助项目(06Z055)

摘　　要：目的:研究组蛋白去乙酰化酶抑制剂丙戊酸钠(VPA-Na)对重度烧伤大鼠脏器功能保护作用的量效关系,探讨VPA-Na有效且更加安全的应用剂量。方法:48只清洁级雄性SD大鼠随机分为4组:烫伤组和VPA-Na低、中、高剂量组,每组12只。采用80℃水浴浸泡背部15 s、双下肢15 s、腹部8 s的方法制备55%TBSAⅢ度烫伤模型,并经病理切片观察证实。制模后,烫伤组大鼠皮下注射生理盐水0.2 ml,VPA-Na低、中、高剂量组分别皮下注射VPA-NA100、200和300 mg/kg。2 h后腹主动脉取血并取心、脑组织,采用全自动生化分析仪测定血浆肌酸激酶同工酶(CK-MB)水平,酶联免疫吸附法(ELISA)检测血浆神经特异性烯醇化酶(NSE)水平,Western blot测定心、脑组织组蛋白H3K9乙酰化(Ac-H3K9)水平。结果:低剂量VPA-Na对烫伤大鼠血浆CK-MB和NSE水平无明显影响(P>0.05),中、高剂量VPA-Na可使其明显降低(P<0.05),高剂量VPA-Na组血浆CK-MB较中剂量组有所升高(P<0.05),但中、高剂量组间血浆NSE水平差异无统计学意义(P>0.05)。VPA-Na可以呈剂量依赖性提高心、脑组织中组蛋白H3K9乙酰化水平(P<0.05),但高剂量与中剂量VPA-Na对脑组织中组蛋白H3K9乙酰化水平的影响差异无显著性(P>0.05)。结论:VPA--Na对重度烧伤大鼠心、脑组织的保护作用与剂量相关;大鼠重度烧伤后皮下注射200 mg/kg VPA-Na是有效保护心、脑功能且更加安全的剂量。Objective：To investigate the dose-effect relationship of valproic acid on protecting vital organs in rats with severe burn inj ury. Methods：Forty-eight Grade Ⅱ male SD rats were randomly divided into 4 groups：scald group and low,medium and high dose of VPA groups,with 1 2 rats in each group. The rats were exposed to 5 5%TBSA of full-thickness thermal injury by immersing the back,both hindlegs and the abdomen in 80 ℃ water for 1 5 ,1 5 and 8 seconds respectively,and the third degree scald inj ury was verified by pathological examination. After the injury,animals received subcutaneous injection of normal saline （0.2 ml）or VPA 100,200 and 300 mg/kg, respectively. The rats were sacrificed,the blood,brain and heart tissues were harvested for examination 2 hours post-inj ury. Plasma creatine kinase MB （CK-MB）and neuron-specific enolase （NSE）levels were assayed by auto-matic biochemical analyzer or ELISA respectively. Histone H3K9 acetylation （Ac-H3K9）level was assayed by Western blotting. Results：Low dose of VPA had no obvious effect on plasma CK-MB and NSE levels （P〉0.05）, but medium and high dose of VPA could decrease the two indicators significantly （P〈0.05）.The high dose of VPA increased plasma CK-MB levels more obviously compared to medium dose of VPA （P〈0.05）,but no statis-tical difference in plasma NSE level between high and medium dose of VPA groups （P〉0.05）.VPA also showed a dose-dependent increase in Ac-H3K9 level in the heart and brain tissues （P〈0.05）,but no significant difference was observed between the results of high and medium dose of VPA groups （P〉0.05）.Conclusions：The protec-tive effect of VPA on brain and heart in burn shock may depend on its dose. Subcutaneous injection of 200 mg/kg VPA to severely burned rats is effective in protecting their vital organs.

关 键 词：丙戊酸钠 烧伤 组蛋白去乙酰化酶抑制剂 

分 类 号：R282.710.5[医药卫生—中药学]