摘要
目的探讨丹参多酚酸盐对心力衰竭(心衰)大鼠心肌肌球蛋白重链(myosin heavy chain,MHC)的影响。方法采用随机数字表法将60只雄性SD大鼠分成6组:正常对照组、模型组、卡托普利组、丹参多酚酸盐低剂量组、丹参多酚酸盐高剂量组、卡托普利和丹参多酚酸盐高剂量联合组(下称中西药联合组),每组10只。除正常对照组外,其余大鼠均采用阿霉素腹腔注射法制备心衰模型,正常对照组大鼠给予等体积生理盐水腹腔注射,每周1次,共6周。从注射阿霉素第5周开始,各用药组给药干预,卡托普利组予100 mg/(kg·d)的卡托普利水溶液灌胃;丹参多酚酸盐低、高剂量组分别以24.219 mg/(kg·d)及48.438 mg/(kg·d)的丹参多酚酸盐溶于2 m L 5%葡萄糖溶液中腹腔注射。中西药联合组予高剂量的丹参多酚酸盐腹腔注射,同时予卡托普利水溶液灌胃,模型组予腹腔注射生理盐水2 m L,每日1次,均连续干预8周。采用生物信号采集处理系统检测心功能、心肌肥厚指数;荧光定量PCR法检测心肌α-MHC及β-MHC mRNA表达;Western blot法检测心肌蛋白激酶C(protein kinase C,PKC)的表达。结果与正常对照组比较,模型组心脏质量指数(heart mass index,HMI)及左室质量指数(left ventricular mass index,LVMI)明显增高(P<0.01);与模型组比较,丹参多酚酸盐高剂量组、卡托普利组、中西药联合组HMI及LVMI均下降(P<0.05,P<0.01),中西药联合组较卡托普利组下降更明显(P<0.05)。与正常对照组比较,模型组心肌组织α-MHC mRNA水平降低,β-MHC mRNA水平及心肌组织PKC表达升高(P<0.01);与模型组比较,丹参多酚酸盐高剂量组、卡托普利组及中西药联合组心肌组织α-MHC mRNA水平升高,β-MHC mRNA水平及心肌组织PKC表达水平均降低(P<0.05,P<0.01),且中西药联合组与卡托普利组比较,差异有统计学意义(P<0.05)。结论丹参多酚酸盐能上调α-MHC并下调β-MHC mRNA水平,其机制可能降低PKC的表达有关。
Objective To explore the effect of Salvianolate on myosin heavy chain（ MHC） in cardiomyocytes of congestive heart failure（ CHF） rats. Methods Sixty male SD rats were divided into 6 groups according to random digit table,i.e.,the normal control group（ NCG）,the model group,the Captopril group（ CAG）,the low dose Salvianolate group（ LSG）,the high dose Salvianolate group（ HSG）,the Captopril and high dose Salvianolate group（ CSG）,10 in each group. CHF rat model was established with peritoneal injection of adriamycin in all rats except those in the NCG. Equal volume of normal saline was peritoneally injected to rats in the NCG,once per week for 6 successive weeks. Corresponding medication was started from the 5th week of injecting adriamycin. Rats in the CAG were administered with Captopril solution at the daily dose of 10 mg / kg by gastrogavage. Rats in the LSG and the HSG were administered with Salvianolate solution at the daily dose of 24. 219 mg / kg and 48. 438 mg / kg respectively by gastrogavage. Salvianolate was dissolved in 2 m L 5% glucose solution and administered by peritoneal injection. Rats in the CSG were peritoneally injected with high dose Salvianolatesolution and administered with Captopril solution by gastrogavage. Two m L normal saline was peritoneally injected to rats in the model group,once per day for 8 successive weeks. Eight weeks later,the cardiac function and myocardial hypertrophy indices were detected by biological signal collecting and processing system. mRNA expression levels of α-MHC and β-MHC in cardiac muscle were detected by fluorescence quantitative PCR. Expressions of protein kinase C（ PKC） in cardiac muscle were detected by Western blot. Results Compared with the normal control group,heart mass index（ HMI） and left ventricular mass index（ LVMI） obviously increased in the model group（P〈0. 01）. Compared with the model group,HMI and LVMI decreased in HSG,CAG,and CSG groups（P〈0. 05,P〈0. 01）. It was more obviously lowered in the CSG group than in the CAG group（P〈0. 05）. Compared with the NCG,the mRNA expression level of α-MHC in cardiac muscle decreased,the mRNA expression level of β-MHC and the expression of PKC in cardiac muscle increased in the model group（P〈0. 01）. Compared with the model group,the mRNA expression level of α-MHC in cardiac muscle was increased,and the mRNA expression level of β-MHC and the expression of PKC in cardiac muscle were decreased in HSG,CAG,and CSG groups（P〈0. 05,P〈0. 01）. There was statistical difference between the CSG group and the CAG group（P〈0. 05）. Conclusions Salvianolate could up-regulate the mRNA expression level of α-MHC,and down-regulate the mRNA expression level of β-MHC in cardiac muscle. Its mechanism might be related to decreasing the expression of PKC.
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2015年第7期871-876,共6页
Chinese Journal of Integrated Traditional and Western Medicine
基金
2011年福建省卫生厅青年科研课题(No.2011-1-41)
2013年福建省中青年教师教育科研项目(科技B类)(No.JB13105)
