依达拉奉预处理对吡喃阿霉素诱导大鼠急性心肌损伤的实验研究

发布时间：2018-03-26 20:06

本文选题：依达拉奉　切入点：吡喃阿霉素　出处：《广西医科大学》2017年硕士论文

【摘要】：目的:观察依达拉奉(EDA)对吡喃阿霉素(THP)诱导的大鼠急性心肌损伤的影响,探讨EDA预处理对大鼠急性心肌损伤是否具有保护作用。方法:取体重230-260克的雌性SD大鼠40只,采用随机数字表法分为四组,每组10只:正常对照组(GNS组)、吡喃阿霉素组(THP组)、EDA-5mg组(EDA-1)、EDA-10mg组(EDA-2)。GNS组于实验第1至第7天每天腹腔注射与EDA等量生理盐水,最后一次注射2h后腹腔注射与THP等量的5%葡萄糖;THP组于实验第1至第7天腹腔注射与EDA等量生理盐水,最后一次注射2h后一次性腹腔注射THP 15mg/kg;EDA-1组于实验第1至第7天腹腔注射低剂量依达拉奉5mg/kg,最后一次注射2h后一次性腹腔注射THP 15mg/kg;EDA-2于实验第1至第7天腹腔注射高剂量依达拉奉10mg/kg,最后一次注射2h后一次性腹腔注射THP 15mg/kg。实验第10天大鼠麻醉后腹主动脉取血,检测血清cTnI和NT-proBNP水平。取血后制作颈动脉标本,光镜下观察病理变化;取心室前壁心肌组织光镜观察病理改变并评分。余心肌组织制作成匀浆,测定·OH、GSH-Px、SOD活性和MDA含量。结果:(1)THP处理后第3天,THP组大鼠的体重较GNS组、EDA-1组、EDA-2组显著降低(P0.05),GNS组、EDA-1组、EDA-2组三组之间体重差异无统计学意义(P0.05)。(2)EDA-1组、EDA-2组和THP组的心脏体重指数比高于GNS组(P0.05),THP组的心脏体重指数高于EDA-1组、EDA-2组(P0.05),EDA-1组和EDA-2组之间无统计学差异(P0.05)。(3)THP组血清cTnI水平明显高于其它三组(P0.05),EDA-1组水平高于EDA-2组(P0.05)。THP组血清NT-proBNP水平也明显高于其它三组(P0.05),两两比较GNS组、EDA-1组、EDA-2组之间无统计学差异。(4)THP组、EDA-1组、EDA-2组·OH活性明显高于GNS组(P0.05),THP组、EDA-1组和EDA-2组两两比较后显示:THP组高于EDA-1组、EDA-2组(P0.05),EDA-1组高于EDA-2组(P0.05)。(5)THP组GSH-Px活性明显低于其它三组(P0.05),THP组、EDA-1组活性低于GNS组活性(P0.05),EDA-2组与GNS组比较无统计学差异(P0.05)。(6)THP组SOD活性低于其它三组(P0.05),EDA-1组、EDA-2组、GNS组活性两两比较差别无统计学意义(P0.05)。THP组MDA含量也明显低于其它三组(P0.05),EDA-1组MDA含量较EDA-2组高(P0.05)。(7)光镜下显示,THP组出现明显的右颈动脉和心肌病理改变,EDA-1组、EDA-2组的病理改变较轻。(8)心肌病理评分:THP组明显高于其它三组(P0.05),EDA-1组、EDA-2组心肌病理评分低于THP组(P0.05),EDA-1组、EDA-2组之间差异无统计学意义(P0.05)。结论:(1)THP可诱发大鼠心肌损伤和颈动脉损伤;(2)EDA5mg/kg、10mg/kg预处理对THP致大鼠心肌急性损伤有一定的保护作用,10mg/kg预处理保护作用更好。
[Abstract]:Objective: to observe the effect of Edaravone on acute myocardial injury induced by pyrrolidine trimethopyranicol (THP) in rats, and to explore whether EDA pretreatment has protective effect on acute myocardial injury in rats. Methods: 40 female SD rats weighing 230 to 260 g were selected. Ten rats in each group were randomly divided into four groups: normal control group (n = 10) and adriamycin group (n = 10). The rats in the control group received intraperitoneal injection of the same amount of normal saline as EDA every day from day 1 to day 7. Two hours after the last injection, 5% glucose was injected intraperitoneally with the same amount of THP as normal saline with EDA on the 1st to 7th day of the experiment. Two hours after the last injection, THP 15mg / kg EDA-1 group was injected intraperitoneally with low dose Edaravone 5mg / kg on the 1st to 7th day, and THP 15mg / kg EDA-2 was injected intraperitoneally at the first to seventh day after the last 2 h injection. The dose of Edaravone was 10 mg / kg, and THP was injected intraperitoneally once 2 hours after the last injection. Blood was taken from abdominal aorta of rats after anesthesia on the 10th day. The serum levels of cTnI and NT-proBNP were measured, the carotid artery specimens were made after blood extraction, the pathological changes were observed under light microscope, the pathological changes were observed and graded by light microscope in the myocardium of the anterior wall of the ventricle, and the remaining myocardial tissue was made into homogenate. Results the body weight of rats in THP group was significantly lower than that in EDA-1 group in GNS group on the 3rd day after THP treatment. There was no significant difference in body weight between EDA-2 group and EDA-2 group (P0.05) and EDA-2 group (THP group). The body mass index of heart in GNS group was higher than that in EDA-1 EDA-2 group and EDA-2 group. There was no significant difference in serum cTnI level between EDA-1 group and EDA-2 group. The level of serum cTnI in THP group was significantly higher than that in other three groups (P0.05EDA-1 group was higher than that in EDA-2 group P0.05TDA-1 group was also higher than that in EDA-2 group. THP group was also significantly higher than EDA-2 group in serum NT-proBNP level. There was no significant difference between EDA-2 group and EDA-2 group in GNS group. The activity of OH in EDA-2 group was significantly higher than that in GNS group P0.05THP group and EDA-2 group. The results showed that the GSH-Px activity of EDA-1 group was higher than that of EDA-1 group EDA-2 group. The GSH-Px activity of EDA-2 group was higher than that of EDA-2 group. The activity of EDA-1 group was lower than that of GNS group. There was no significant difference in SOD activity between GNS group and GNS group. There was no significant difference in MDA content between EDA-2 group and GNS group. The content of MDA in EDA-1 group was significantly lower than that in EDA-2 group (P 0.05). The pathological changes of right carotid artery and myocardium in EDA-1 group were significantly higher than those in EDA-2 group. The pathological changes of right carotid artery and myocardium in EDA-2 group were significantly lower than those in EDA-2 group (P 0.05) and EDA-1 in other three groups were significantly higher than that in other three groups. There was no significant difference between EDA-2 group and THP group (P 0.05g / kg). Conclusion THP can induce myocardial injury and carotid artery injury in rats. [WT5 "HZ] EDA-2 / 10 mg / kg / kg preconditioning has a protective effect on acute myocardial injury induced by THP in rats (10 mg / kg / kg). The protective effect of pretreatment is better.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R614

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