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was recorded,and the average survival time and 24 h survival rate of rats in each group were calculated. Mean arterial pressure
(MAP),heart rate(HR),respiration rate(RR),rectal temperature(RT),arterial blood pH,arterial partial pressure of oxygen
(PaO2 ),arterial blood partial pressure of carbon dioxide(PaCO2 ),HCO3 ,creatine kinase MB isoenzyme(CK-MB)and neuron
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specific enolase(NSE)were detected before scalding,at 0,2,5 h after scalding. The pathological changes of cardiac and cerebral
tissue were observed. RESULTS The 24 h survival rate of group SS(55%)was significantly lower than that of group S(90%),
while that of group SSV(75%)was increased significantly,compared with group SS(P<0.05). Compared with group S,the
- in group SS were significantly lowered,while the levels of CK-MB and NSE
levels of MAP,RT,HR,pH,PaO2 and HCO3
were increased significantly at 0,2,5 h after scalding;the levels of PaCO2 were increased significantly at 2,5 h after scalding,
while the levels of RR were decreased significantly at 0,2 h after scalding(P<0.05). Compared with group SS,the levels of
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MAP,RT,HR,pH,PaO2 and HCO3 in group SSV were significantly increased,while the levels of PaCO2,CK-MB and NSE
were decreased significantly at 2,5 h after scalding;the level of RR was increased significantly at 2 h after scalding(P<0.05). At
2,5 h after scalding,cardiac and cerebral injury of rats in group SS were aggravated significantly than that in group S;cardiac
and cerebral injury of rats in group SSV were relieved significantly than that in group SS. CONCLUSIONS After severe scalding
combined seawater immersion injury,hypodermic injection of sodium valproate could protect cardiac and cerebral function of rats,
improve vital signs and blood gas index,prolong survival time and improve survival rate in rats.
KEYWORDS sodium valproate;Severe scalding;seawater immersion;histone deacetylase inhibitors;delayed fluid replacement
随着人类海洋活动的增加,海难或海战时落海伤员 1.3 人工海水
常同时伴有烧伤和海水浸泡。由于海上环境特殊,医疗 人工海水按照国家海洋局第三海洋研究所提供的
救助受限,往往难以及时开展有效的静脉液体复苏,导 海水主要成分配制,其渗透压为(1 250±11)mmol/L,
致伤员死亡率升高,救治难度增加 。若在伤后早期给 pH为8.20,含钠离子(630±5)mmol/L、钾离子(10.88±
[1]
予抗休克维持药物,提高机体对休克的耐受能力,保护 0.68)mmol/L、氯 离 子(658.8 ± 5.5)mmol/L,温 度 为
心脑等重要脏器功能,就能为后续救治争取时间,从而 (23±1)℃。
提高伤员生存率。丙戊酸钠是一种组蛋白去乙酰化酶 1.4 动物
抑制剂,既往研究发现,在失血性休克或致死性烫伤动 雄性SD大鼠180只,60~70日龄,体质量250~300 g,
物实验中,丙戊酸钠能保护重要脏器功能,提高动物生 购自斯贝福(北京)生物技术有限公司,生产许可证号为
存率 [2-5] 。因此,本研究通过构建严重烫伤合并海水浸 SCXK(京)2019-0010。购进后,大鼠适应性饲养于22~
泡延迟补液大鼠模型,并在烫伤后立即皮下注射大剂量 25 ℃的饲养房内1周以上,自由饮食。大鼠饲养与实验
丙戊酸钠,从而探究其对大鼠损伤心脑的保护作用,以 过程均严格遵守实验动物管理与保护准则。
期为丙戊酸钠用于烧伤合并海水浸泡伤员的救治提供 2 方法
实验依据。 2.1 分组、造模与给药
1 材料 将大鼠按照随机数字表法分为烫伤+延迟补液组(S
1.1 主要仪器 组)、烫伤+海水浸泡+延迟补液组(SS组)、烫伤+海水浸
PowerLab 型多导生理记录仪购自澳大利亚 ADIn- 泡+丙戊酸钠+延迟补液组(SSV 组),每组 60 只。术前
struments公司;RAPIDPoint 500型血气分析仪购自德国 禁食 12 h、自由饮水,所有大鼠称定体质量后给予戊巴
Siemens公司;KD-BM型生物组织包埋机购自金华市科 比妥钠30 mg/kg腹腔注射麻醉,固定、消毒,解剖分离一
迪仪器设备有限公司;CKX53 型倒置显微镜购自日本 侧颈总动脉、静脉,分别插管,剪除颈背部和臀部毛发。
Olympus公司;ST360型酶标仪购自上海科华生物工程股 采用沸水水浴法建立Ⅲ度烫伤模型:将大鼠颈背部和臀
份有限公司;数字测温仪购自衡水创纪仪器仪表有限公司。 部浸泡于 100 ℃沸水中 15 s 造成 35%总体表面积Ⅲ度
1.2 主要药品与试剂 烫伤,烫伤深度经病理组织切片检查证实。SS组和SSV
丙戊酸钠对照品(批号B2013169,纯度≥98%)购自 组大鼠烫伤后立即浸泡于人工海水中(30 min),其中
上海阿拉丁生化科技股份有限公司;戊巴比妥钠(批号 SSV组出水后即刻皮下注射丙戊酸钠300 mg/kg [6-7] 。烫
P3761,纯度≥98%)购自美国 Sigma 公司;乳酸钠林格 伤后2 h,各组按1/2 Parkland公式(4 mL×1%烧伤面积×
注射液(批号2010242107,规格500 mL)购自石家庄四药 kg)于30 min内静脉注射乳酸钠林格注射液进行延迟补
[8]
有限公司;肌酸激酶同工酶(creatine kinase MB isoen- 液,在烫伤后的第1个8 h补入总量的1/2 。
zyme,CK-MB)和神经元特异性烯醇化酶(neuron specif- 2.2 大鼠生存情况观察
ic enolase,NSE)酶联免疫吸附测定试剂盒(批号分别为 每组取 20 只大鼠。S 组烫伤后即刻观察,SS 组和
202107、202104)均购自上海江莱生物科技有限公司。 SSV组海水浸泡后开始观察,每30 min观察1次,连续观
·2114 · China Pharmacy 2022 Vol. 33 No. 17 中国药房 2022年第33卷第17期