加减木防己汤对缺血性心力衰竭大鼠心肌肌浆网Ca^(2+)-ATP酶及心肌重构的影响

Effects of Altering Cocculus Decoction on Ca^(2+)-ATPase and Myocardial Remolding in Ischemic Heart Failure Rats

目的:探讨加减木防己汤对缺血性心力衰竭(ischemic heart failure IHF)大鼠心室重构的影响及其作用机制。方法:60只雄性SD大鼠,冠脉结扎法制备IHF模型,选取6只为假手术组(只穿线不结扎),将造模成功大鼠随机分为模型组(6只)、西药组(6只)、中药高剂量组(6只)、中药中剂量组(6只)及中药低剂量组(6只)5组。假手术组和模型组给予1.0 m L/(100 g·d)纯净水灌胃;中药高、中、低剂量组(8、4、2g/m L)分别予等体积加减木防己汤灌胃;西药组予5 mg/(100 g·d)卡托普利灌胃,持续4周。心脏超声、血浆TNF-α、AngⅡ、IL-6、ET-1浓度测定及免疫组化测SERCA2a含量。结果:与假手术组比较,模型组的射血分数(EF)、实际面积和IOD阳性指数明显降低(P<0.05),左室收缩末期内径(LVS)、左室后壁厚度(LVPWD)明显升高(P<0.05);与模型组比较,西药对照组、中药低、中、药高剂量组EF明显升高(P<0.05),中药低、中、高剂量组LVS明显下降(P<0.05);中药3组室间隔厚度(IVSD)、LVPWD无明显改变(P>0.05),中药高剂量组实际面积明显升高(P<0.05),中药中剂量组IOD阳性指数明显升高(P<0.05);与西药对照组比较,中药高剂量组EF明显升高(P<0.05),中药中、高剂量组LVS明显下降(P<0.05),中药3个剂量组实际面积和IOD阳性指数无明显改变(P>0.05)。结论:西药和中药均能改善大鼠心功能,主要表现为对收缩功能改善;中高剂量中药在改善收缩功能方面优于西药;中高剂量中药能显著增加心肌SERCA2a含量,但中药未能改善心肌重构。

Objective： To study the effects and mechanisms of altering Cocculus Decoction on the ventricular remodeling of ischemic heart failure rats. Methods： Six rats were selected from sixty SD male rats as the sham operation group and the rest were used to prepare IHF rat model by coronary artery ligation. The successfully modeled rats were randomly divided into five groups,i. e.,the model group（n = 6）,the Western medicine group（n = 6）,the Chinese medicine high dose group（n = 6）,middle dose group（n = 6） and low dose group（n = 6）. Routine gavage of equal volume purified water1. 0 mL/100（g·d） was given to rats in the sham operation group and the model group respectively. Three doses（8,4,2g/mL） altering Cocculus Decoction were given in same volume to rats. Captopril was given to rats in the Western medicine group at 5 mg/100（g. d）. The medication lasted for four successive weeks. Echocardiography,plasma concentration levels of TNF-α,Ang Ⅱ,IL-6,ET-1 and content of SERCA2 a were measured. Results： Compared with sham operation group,EF,the actual area and IOD positive index decreased significantly（P〈0. 05） while LVS and LVPD increased significantly（P〈0. 05） in model group. Compared with the model group,EF increased significantly（P〈0. 05） in western medicine group and Chinese medicine three dosage groups while LVS decreased significantly（P〈0. 05）; but IVSD and LVPW value showed no significant statistical change（P〈0. 05） in Chinese medicine three dosage groups. The actual area increased significantly（P〈0. 05） in Chinese medicine high dose group while IOD positive index increased significantly（P〈0. 05） in Chinese medicine mid dose group. Compared with the control group of Western medicine,EF significantly increased（P〈0. 05） in Chinese medicine high dose group and LVS of high dose group decreased significantly（P〈0. 05）; actual area and IOD positive index had no significant difference（P〉0. 05） in traditional Chinese medicine three dose groups. Conclusion： Both the western medicine and traditional Chinese medicine can improve rats heart function while mid-high dose of Chinese medicine is superior to western medicine in improving the left ventricular systolic function; mid-high dose Chinese medicine could significantly increase myocardial SERCA2 a content but fails to improve myocardial remodeling.