藻酸双酯钠纳米剂型对糖尿病心肌病左室功能的影响

Effect of propylene glycol alginate sodium sulfate nanoparticles on left ventricular function during the rat model of diabetic cardiomyopathy

目的探究藻酸双酯钠纳米剂型(PSS-NP)对糖尿病心肌病(DCM)左室功能的影响。方法 43只大鼠注射链脲佐菌素(STZ)诱导DCM模型,7只大鼠注射0.1%柠檬酸缓冲液(PBS)作为对照。诱导后8周,将成模大鼠随机分为DCM组、溶媒羧甲基纤维素钠(CMC-Na)组、阳性对照药组、藻酸双酯钠(PSS)组、藻酸双酯钠纳米剂型(PSS-NP)组,分别给予生理盐水、0.5%CMC-Na、德纳+0.5%CMC-Na、PSS+0.5%CMC-Na、PSS-NP+0.5%CMC-Na灌胃6周,STZ诱导后8、16周评估DCM大鼠心功能,实验末检测血脂代谢指标(TG、TC、LDL-C、HDL-C)及凝血指标(FIB、PT、APTT),苏木精-伊红(HE)染色评价心肌组织变化。结果与正常对照组比较,DCM组大鼠一般状况变差,血糖、心脏质量与体重比值、TG、TC、LDL-C、FIB明显升高,体重、HDL-C、PT、APTT、LVEF、FS、E/A、Em/Am明显降低,LVEDd、LVEDs增加,HE染色示心肌纤维紊乱、细胞肥大、细胞核大小不均。与DCM组比较,溶媒组大鼠各项差异无统计学意义(P>0.05),PSS、PSSNP组血糖明显降低(P<0.05),3组药物干预组大鼠体重、LVEF、FS、E/A、Em/Am增加(P<0.05),LVEDd、LVEDs降低(P<0.05),血脂代谢指标及凝血指标改善显著(P<0.05),HE染色示心肌受损改善,与PSS组比较,PSS-NP组左室功能显著改善(P<0.05)。结论 PSS-NP对糖尿病大鼠左室功能具有改善作用,可能为DCM心功能不全的治疗药物。

Objective To investigate the effects of propylene glycol alginate sodium sulfate nanoparticles on left ventricular function of DCM rats.Methods Diabetes cardiomyopathy（DCM）was induced in 43 male Wistar rats by a single intraperitoneal injection of streptozotocin.7rats were injected of vehicle（0.1mol/L sodium citrate buffer）in the same way as the control.Eight weeks after the induction,the survival DCM model rats were randomly divided into DCM group,the vehicle CMC-Na group,positive control drug dorner group,the PSS group,the PSS-NP group,intragastric administrated for six weeks.Eight and sixteen weeks after the induction,the echocardiographic and Doppler ultrasonography were used to evaluate the cardiac function,and detect blood lipid metabolism index（TG,TC,LDL-C,HDL-C）and coagulation function index（FIB,PT,APTT）.Hematoxylin and eosin（HE）staining was applied to observe the myocardial tissue.Results Compared with the control group,DCM group showed that the blood glucose increased;body weight decreased;the ratio of the heart weight and the body weight increased;TG,TC,LDL-C rose obviously;significantly lower HDL-C;FIB obviously increased;LVEF,FS,E/A,Em/Am,PT,APTT significantly reduced;statistically significant difference（P〈0.05）;the LVEDd and LVEDs increased.Myocardial fibers disorder,myocyte hypertrophy and the different size of the nuclei were shown by HE staining.The differences between DCM group and vehicle group showed no statistical significance（P〉0.05）.Compared with DCM group,the PSS,PSS-NP groups showed that the blood glucose was significantly decreased（P 0.05）,the body weight,LVEF,FS,E/A,Em/Am were increased（P〈0.05）,the LVEDd and LVEDs decreased（P〈0.05）.HE staining showed the myocardial injury improved.Compared with DCM group,the PSS-NP effect of improving cardiac function was significant（P〈0.05）.Conclusion PSS-NP improved the left ventricular dysfunction in diabetic rats,and might be the new formulation for diabetic cardiomyopathy left ventricular function disturbance.