左卡尼汀对慢性肾衰竭大鼠心脏的保护作用  

Heart protection of L-carnitine in chronic renal failure rats

作　　者：张黎明[1] 唐琦[1] 梅长林[2] 芦怡舟[1] 邬碧波[1] 

机构地区：[1]上海市闸北区中心医院肾内科,200070 [2]第二军医大学长征医院肾内科解放军肾脏病研究所

出　　处：《中华肾脏病杂志》2012年第5期377-382,共6页Chinese Journal of Nephrology

基　　金：上海市卫生局科技发展基金（2009255）;上海市闸北区卫生局科研基金（2009ZBMXK02）

摘　　要：目的观察左卡尼汀对慢性肾衰竭大鼠心脏病理变化的影响，并探讨其心脏保护机制。方法55只雄性SD大鼠按数字随机法分为假手术组（n=10）、模型组（n=15）、左卡尼汀小剂量组（n=10）、中剂量组（n=10）和大剂量组（n=10）。除假手术组外，其余各组大鼠行5／6肾切除术。造模后1周，各左卡尼汀组大鼠每日灌胃给药，剂量分别为300、600、900mg／kg。假手术组和模型组则每日予生理盐水灌胃，总疗程17周。观察大鼠24h尿蛋白量、肾功能、超氧化物歧化酶（SOD）、丙二醛（MDA）、白介素6（IL-6）、三磷酸腺苷（ATP）、二磷酸腺苷（ADP）变化。实验结束时，测各组大鼠平均动脉压及心率，并通过心脏超声、全心／体质量比、光镜、透射电镜观察大鼠心脏病理变化。结果（1）左卡尼汀小、中、大剂量组ATP（μmol／g体质量）（2．35±0．24，3．59±0．28，3．78±0．25）均显著高于模型组（1．61±0．12）（均P〈0．01）。（2）心脏超声显示左卡尼汀大剂量组左心室后壁厚度（mm）小于模型组（3．74±0．23比4．18±0．48，P〈0．05）。（3）左卡尼汀中、大剂量组全心／体质量比值（3．92±0．27，3．65±O．20）均显著低于模型组（3．99±0．27）（P〈0．01）。（4）光镜下，HE染色显示模型组心肌细胞排列紊乱，心肌细胞肥大；Masson染色显示胶原组织明显增多，部分心肌组织被胶原组织取代，出现心肌间质纤维化。HE染色显示左卡尼汀中、大剂量组心肌细胞排列紊乱；Masson染色显示心肌组织周围胶原纤维增多，心肌间质纤维化，但病变程度和范围均明显减轻。左卡尼汀中、大剂量组心肌病理评分（7．14±1．07，6．13±0．99）均低于模型组（9．88±1．13）（P〈0．01）。电镜下，模型组可见大片心肌纤维溶解，线粒体增多、肿胀、空泡化，膜断裂、基质加深，为典型�Objective To investigate the effect of L-carnitine on pathological changes of myocardium and the underlying mechanism in chronic renal failure rats （CRF）. Methods A total of 55 male SD rats were randomly divided into sham group （n=10）, model group （n=15）, low dose （300 mg/kg）, medium dose （600 mg/kg） and high dose （900 mg/kg） L-carnitine group（n=10, each）. 5/6 subtotal nephrectomy was performed in these rats without sham group. One week after the operation, normal saline or corresponding dose L-carnitine were intragastrically administrated to sham and model group or L-carnitine groups for 17 weeks. Transthoracic echocardiography, mean arterial pressure （MAP）, heart rate （HR） and heart weight/body weight were assessed. Moreover, 24 h urine protein, renal function, SOD, MDA, IL-6, ATP, ADP were measured at the end of the study. Additionally, pathological changes in myocardium were detected by light microscope and transmission electron microscope. Results （1） ATP （μmol/g wt）in L-carnitine groups （2.35±0.24, 3.59±0.28,3.78±0.25） was significantly higher than that in model group （1.61±0.12） （all P〈0.01）. （2） Thickness of posterior wall of left ventricle （mm） in high dose L-camitine group was thinner than that in model group （3.74±0.23 vs 4.18±0.48, P〈0.05）. （3） The ratios of heart weight to body weight in both medium dose and high dose L-carnitine groups （3.92±0.27, 3.65± 0.2） were significantly lower compared to model group （3.99±0.27） （all P〈0.O1）. （4） Under light microscopy, disarrangement and hypertrophy of cardiac myocytes, increased myocardial fibrosis were observed in model group, while these changes and the pathological scores were significantly improved in both medium dose and high dose L-camitine groups （7.14±1.07, 6.13±0.99）, as compared with model group （9.88±1.13） （all P〈0.01）. Under electron microscopy, typical changes in cardiac hypertrophy were observed, including dissolution of myoc

关 键 词：左卡尼汀 慢性肾衰竭 大鼠 心脏 

分 类 号：R692[医药卫生—泌尿科学]