辛伐他汀对阿霉素致心衰兔心功能的影响

The Effects of Simvastatin on Adriamycin-induced Heart Failure in Rabbits

目的:探讨不同剂量辛伐他汀对阿霉素所致心衰兔保护作用及其抗心衰的机制。方法:雄性新西兰大耳白兔60只,随机数字表法分为正常对照组(CON)、CHF模型组(CHF)、CHF+辛伐他汀低剂量组(LD-SIM)、CHF+辛伐他汀中剂量组(MD-SIM)、CHF+辛伐他汀高剂量组(HD-SIM)。正常对照组(CON)给予耳缘静脉等体积生理盐水,每周1次,共10周。其余组均给予生理盐水注射液稀释的盐酸阿霉素,按4 mg/kg,每周1次,共10次,而辛伐他汀干预组同时给予低、中、高剂量辛伐他汀灌胃治疗,剂量分别为0.3 mg/(kg·d),1.5 mg/(kg·d),3.0 mg/(kg·d)。10周后测定大鼠心功能左室肥厚指数、ELISA测定血清中hs-CRP和MMP-13含量。结果:各药物治疗组可不同程度改善左室肥厚,其中辛伐他汀大剂量组与CHF模型组比较差异有统计学意义(P<0.01),而辛伐他汀中剂量组与其比较差异有统计学意义(P<0.05),而小剂量治疗组与之比较差异无统计学意义(P>0.05);大中剂量治疗组心功能指标(±dp/dtmax)明显优于模型组,差异有统计学意义(P<0.01),辛伐他汀大剂量组与中剂量组比较差异无统计学意义(P>0.05),而小剂量治疗组与模型组比较差异无统计学意义(P>0.05);各药物治疗组能降低血清中CRP、MMP-13含量(P<0.01或P<0.05)。结论:辛伐他汀能够预防左心肥厚,降低血浆CRP、MMP-13浓度,从而减缓细胞外基质(ECM)的降解改善心功能,这可能是辛伐他汀抗心衰作用机制之一。

Objective：To explore the protective effect and molecular mechanism of different dosages simvastatin on adriamycin-induced heart failure rabbits.Method：Sixty male rabbits were randomly divided into five groups：control group （CON）,chronic heart failure group（CHF）,simvastatin at a small dosage group（LD-SIM）,simvastatin at a moderate dosage group（MD-SIM）and simvastatin at a large dosage group（HD-SIM）.The control group was given ear vein and＆amp;nbsp;normal saline,1 times a week,for 10 weeks,the other groups were given physiological saline injection diluted hydrochloric doxorubicin,at 4 mg/kg,1 times per week,a total of 10 times,and simvastatin group was given gavage treatment in small,moderate and large dose simvastatin,dose were 0.3 mg/（kg·d）,1.5 mg/（kg·d）,3.0 mg/（kg·d）.After ten-weeks treatment,measured the ventricular hypertrophy index（LVHI）and plasma levels of high sensitive C-protein and MMP-13 by ELISA.Result：Compared with the CHF group,the left ventricular hypertrophy were improved in different degrees in the simvastatin treatment groups,in which the effect of the large dosage group was obvious（P〈0.01）,moderate dosage group had statistically significant（P〈0.05）,while the small dosage treatment group showed no significant change （P〉0.05）;The heart function indexes（±dp/dtmax）in large dosage group and moderate dosage group were significantly better than those of model group（P〈0.01）,but no significant difference between the two treatment groups（P〉0.05）,and the small dosage treatment group compared with the model group had no significant difference（P〉0.05）;The treatment group could reduce the plasma levels of CRP and MMP-13（P〈0.01 or P〈0.05）.Conclusion：Simvastatin can prevent left ventricular hypertrophy,and decrease plasma CRP,MMP-13 concentration,thereby prevent the extracellular matrix（ECM） degradation and improve heart function,which may be one of the mechanisms of simvastatin anti heart failure.