链脲佐菌素诱导MSG大鼠糖尿病心脏病模型的研究

目的:探讨腹腔注射链脲佐菌素(Streptozotocin,STZ)诱导L-谷氨酸钠(Monosodium glutamate,MSG)肥胖大鼠建立糖尿病心脏病模型。方法:选用新生SD大鼠随机分为两组:MSG组和正常对照组(NS组)。MSG组新生大鼠自出生第2d起颈部皮下注射L-谷氨酸钠5g·kg-1,隔天一次,共三次;正常对照组于皮下注射等体积无菌注射用水。MSG组于6周龄时再随机分为4个小组,腹腔注射链脲佐菌素0mg·kg-1,20mg·kg-1,30mg·kg-1,40mg·kg-1。于注射STZ 4w后测定各心脏血流动力学相关指标,同时取血测定其胰岛素水平及血液脂质等指标。结果:注射STZ 4w后,MSG组大鼠Lee’s指数显著增加,心脏指数明显降低,血浆高密度胆固醇(HDL)、低密度胆固醇(LDL)升高,收缩压(SBP)、舒张压(DBP)、平均动脉压(MAP)、心率(HR)、左心室收缩压(LVSP)、左心室内压最大上升速率(+dp/dt)、下降速率(-dp/dt)均显著升高,心电图显示其Q-T间期缩短,与对照组比较有统计学差异。MSG+STZ 30mg·kg-1组大鼠SBP、DBP、MAP、HR、+dp/dt、-dp/dt均显著降低,与MSG组比较有统计学差异。MSG+STZ 40mg·kg-1组大鼠SBP、DBP、MAP、HR、LVSP、+dp/dt、-dp/dt均显著降低,Lee’s指数降低,胰岛素浓度降低,血糖水平及心脏指数升高,血浆LDL水平降低,Q-T间期延长,与MSG组比较有统计学差异。结论:研究表明MSG大鼠在6周龄时腹腔注射STZ 40mg·kg-1,有利于糖尿病心脏病模型的建立,为研究、开发防治2型糖尿病心脏病的新药提供了一种良好的动物模型。

Study on streptozotocin induced diabetic cardiopathy in MSG rats

Objective： To investigate the effect of streptozotocin （Streptozotoein, STZ） intraperitoneal hliection to induce diabetic cardiopathy in the obese rat induced by sodium glutamate （L-Mono-sodium glutamate, MSG）. Methods： The neonatal SD rats were randomly divided into two groups： MSG group and normal control group （NS group）. The MSG rats were subcutaneous injection of L-sodium glutamate 5 g · kg-1 from birth the very next day, for three times; and the normal control rats were injected with equal volume of sterile water. 6 weeks later, the MSG treated rats were randomly divided into four groups, which were intraperitoneal in- iected with streptozotocin 0 mg · kg-1 , 20 mg· kg-1 , 30 mg· kg-1 or 40 mg· kg-1 respectively. At 4 weeks after injection of STZ, the cardiac hemodynamics, plasma insulin, glucose and lipid content were measured. Results.- 4 weeks after STZ injection, compared with the normal control rats, Lee＇s index was significantly higher, cardiac index was significantly lower. The plasma levels of HDL, LDL, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, mean arterial pressure （MAP）, heart rate （HR）, left ventricular systolic pressure （LVSP）, left heart interior maximum pressure rise rate （H- dp/dt）, decline rate （dp/dt） were significantly increased, ECG showed to shorten the Q-T interval in MSG rats （P〈0.01）. Compared with the MSG group, MSG＋STZ30 mg·kg-lcan significantly decreased SBP, DBP, MAP, HR, ＋dp/dt, --dp/dt. MSG-kSTZ40 mg · kg-1 can also significantly decreased SBP, DBP, MAP, HR, -Fdp/dt, --dp/dt, the Lee＇s index and levels of insulin and LDL. Moreover, MSG＋ STZ40 mg · kg-1 can significantly increased the blood glucose level and cardiac index, and prolong the Q-T interval markedly. Conclusion： Diabetic heart disease model in 6 weeks of MSG was established by intraperitoneal injection of STZ at the dose of 40 mg· kg-1. It is a good animal model provided for the research, development, prevention and cure type 2 diabetic heart disease drugs.