曲美他嗪对小鼠心肌损伤的保护研究  

Protective Effect of Trimetazidine on Myocardial Injury in Mice

作　　者：郑二女 苏显明[1] 樊蓉 

机构地区：[1]西安交通大学第一附属医院老年心血管内科,710061 [2]西安一四一医院老年内科,710089

出　　处：《医学研究杂志》2017年第10期56-59,共4页Journal of Medical Research

基　　金：陕西省自然科学基金资助项目(2016JM8082)

摘　　要：目的研究盐酸曲美他嗪(TMZ)对异丙肾上腺素(ISO)所致小鼠心肌损伤的保护作用。方法 6~7周龄BALB/c小鼠36只,随机分为3组(每组12只),生理盐水(NS)组、ISO组、TMZ组;NS组为空白对照组,ISO组为损伤组,TMZ组为治疗组,共喂养4周。计算心脏质量指数(HW/BW%),微量酶标法测定血清乳酸脱氢酶(LDH)活性、硫代巴比妥酸(TBA)法测定丙二醛(MDA)含量、WST-1法测定超氧化物歧化酶(SOD)活力、ELISA法检测血清Klotho浓度,心肌组织石蜡包埋行HE染色、Massion染色、caspase-3染色。结果与NS组比较,ISO组HW/BW、乳酸脱氢酶(LDH)活性、丙二醛(MDA)含量均显著增加(P<0.01),SOD活力显著减低(P<0.01);TMZ组的HW/BW、LDH活性、MDA含量均显著低ISO组(P<0.01),SOD活力、Klotho浓度显著高于ISO组(P<0.01),HE染色结果显示,ISO组小鼠心肌细胞横径明显大于NS对照组,伴随着肌纤维紊乱和心肌间质成纤维细胞增生。TMZ组小鼠心肌细胞横径明显小于ISO组;Masson染色结果显示,ISO组小鼠心肌间质及血管壁有大量胶原纤维分布,而TMZ组小鼠的心肌间质及血管壁胶原纤维数量较ISO组明显减少;caspase-3染色结果:TMZ组棕黄色染色颗粒分布较ISO组明显减少(染色阳性结果表现为胞质中有大量棕黄色染色颗粒分布)。结论曲美他嗪可以防止心肌损伤,其机制可能与上调Klotho水平有关。Objective To study the protective effect of Trimetazidine on myocardial injury in mice. Methods 6 to 7 week - old male BALB/c mice were randomly divided into 3 groups at twelve for each group： normal saline （NS） group,ISO group and TMZ group, N. S group for blank control group, ISO group for damage group, TMZ as treatment group. After 4 weeks, cardiac index （HW/BW） was calculated, serum lactate dehydrogenase （LDH） activity were measured by enzyme standard method. Malondialdehyde（MDA） was detec- ted by thiobarbiturie acid method（TBA）. Superoxide dismutase （SOD） activity were determined by WST - 1 method. The concentrations of serum Klotho were measured by ELSIA. The cardiac muscular tissue was imbedded with paraffin and colored with HE, Massion and caspase -3. Results The experiment model meets the requirements. In TMZ groups＇ HW/BW, LDH activity and MDA level were sig- nificantly lower than those of the ISO group（P 〈 0.01 ）. SOD energy, concentration of Klotho was significantly higher than those of the ISO group（ P 〈 0.01 ）. HE color results showed that the myocardial cell diameter of ISO group was obviously larger than that of NS group, combined with disordered muscle fibers and hyperplastic myocardial interstitial fibroblasts. The eardiomyocytes diameter of TMZ groups was much smaller than that of the ISO group. Masson color results showed that the level of collagen fiber distribution in the myocardial in- terstitial and hemal wall of TMZ group was lower than that of ISO group. Caspase 3 color results showed that the number of tan dye distri- bution was significantly lower in TMZ group than that of the ISO group（ Color positive results showed obvious practical color distribution）. Conclusion Trimetazidine could prevent myocardial injury and its mechanism might be related to raised Klotho level.

关 键 词：KLOTHO 盐酸曲美他嗪 心肌损伤 氧化应激 异丙肾上腺素 小鼠 

分 类 号：R3[医药卫生—基础医学]