SIPI-7623与辛伐他汀联合用药对高脂血症大鼠的降血脂作用

Blood lipid regulation effects of SIPI-7623 combined with simvastatin in hyperlipidemic rats

目的探讨SIPI-7623与辛伐他汀联合用药对高脂血症大鼠的降血脂作用。方法所有大鼠分为空白组、模型组、SIPI-7623低剂量组(20 mg/kg)、SIPI-7623中剂量组(40 mg/kg)、SIPI-7623高剂量组(80 mg/kg)、辛伐他汀低剂量组(5 mg/kg)、辛伐他汀高剂量组(10 mg/kg)、联合给药低剂量组(SIPI-762320 mg/kg+辛伐他汀5 mg/kg)及联合给药高剂量组(SIPI-762340 mg/kg+辛伐他汀5 mg/kg),每组6只。除空白组外,其他各组大鼠均按体质量给予脂肪乳剂灌胃造模。造模成功后分别给予相应干预药物。连续给药21 d后测定大鼠血脂指标,包括总胆固醇(total cholesterol,TC)、三酰甘油(triglyceride,TG)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)及低密度脂蛋白胆固醇(lowdensity lipoprotein cholesterol,LDL-C),并计算相应抑制率。处死大鼠后取肝脏进行苏木精-伊红染色切片并在镜下观察病理变化情况。测定大鼠谷丙转氨酶(alanine aminotransferase,AST)、谷草转氨酶(aspartate aminotransferase,AST)、肌酸激酶(creatine kinase,CK)及肌酸激酶同工酶(CK-MB)以观察安全性。结果SIPI-7623各剂量组、联合给药各剂量组及辛伐他汀高剂量组大鼠TC、TG及LDL-C水平低于模型组(P<0.05或P<0.01)。SIPI-7623低、中及高剂量组对TC的抑制率分别为41.34%、42.61%和46.30%,对TG的抑制率分别为53.06%、56.12%和68.37%,对LDL-C的抑制率分别为46.84%、46.84%和56.98%。联合给药低剂量组及高剂量组对TC的抑制率分别为53.35%和52.23%,对TG的抑制率分别为63.27%和65.30%,对LDL-C的抑制率分别为65.05%和61.67%。辛伐他汀高剂量组对TC、TG及LDL-C的抑制率分别为39.26%、53.06%和42.43%。各组间大鼠ALT、AST、CK及CK-MB差异均无统计学意义(P>0.05)。病理观察结果显示,联合给药各剂量组和SIPI-7623中、高剂量组大鼠肝脏病理变化情况优于其他各组。结论SIPI-7623具有降低血脂的作用,且与辛伐他汀联用效果优于单独使用SIPI-7623和辛伐他汀。

Objective To investigate the blood lipid regulation effects of SIPI-7623 combined with simvastatin in hyperlipidemic rats.Methods All rats were divided into blank group,model group,SIPI-7623 low dose group(20 mg/kg),SIPI-7623 medium dose group(40 mg/kg),SIPI-7623 high dose group(80 mg/kg),simvastatin low dose group(5 mg/kg),simvastatin high dose group(10 mg/kg),combined treatment low dose group(SIPI-762320 mg/kg+simvastatin 5 mg/kg)and combined treatment high dose group(SIPI-762340 mg/kg+simvastatin 5 mg/kg),each group 6 cases.In addition to the blank group,rats in other groups were given fat emulsion by gavage according to body weight.After the success of the model,the corresponding intervention drugs were given.After 21 days of continuous administration,the indexes of blood lipid were measured,including total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C),and the corresponding inhibition rate was calculated.After the rats were killed,the liver was taken for hematoxylin eosin staining and the pathological changes were observed under the microscope.In addition,alanine aminotransferase(AST),aspartate aminotransferase(AST),creatine kinase(CK)and CK-MB were measured to observe the safety.Results The levels of TC,TG and LDL-C in SIPI-7623,combined dose groups and simvastatin high-dose groups were lower than those in the model group(P<0.05 or P<0.01).The inhibitory ratesv(IR)of SIPI-7623 low dose group,medium dose groupon and high dose group on TC were 41.34%,42.61%and 46.30%.The IR of SIPI-7623 low dose group,medium dose groupon and high dose group on TG were 53.06%,56.12%and 68.37%.The IR of SIPI-7623 low dose group,medium dose group on and high dose group on LDL-C were 41.34%,42.61%and 46.30%.The IR of combined treatment low dose group and high dose group on TC were 53.06%,56.12%and 68.37%.The IR of combined treatment low dose group and high dose group on TG were 46.84%,46.84%and 56.98%.The IR of combined treatment low dose group and high dose group on LDL-C were 53.35%and 52.23%.The IR of TC,TG and LDL-C in high dose simvastatin group were 39.26%,53.06%and 42.43%.There was no significant difference in ALT,AST,CK and CKMB among the each group(P>0.05).The results of pathological observation showed that the pathological changes in the liver of rats in each dose group and SIPI-7623 medium and high dose groups were better than the other groups.Conclusion SIPI-7623 can regulate the blood lipid effeectively,and the combination effect of SIPI-7623 and simvastatin is superior to SIPI-7623 or simvastatin alone.