复方丹参滴丸对实验性心肌肥厚大鼠心肌氧化应激指标和炎性因子的影响

Effect of compound Danshen dripping pill on myocardium and myocardial oxidation index and inflammatory factors in rats with experimental myocardial hypertrophy

目的探讨复方丹参滴丸对心肌肥厚大鼠心肌氧化应激指标和炎性因子的影响。方法将36只雄性Sprague Dawley大鼠随机分为对照组、模型组、卡托普利组及复方丹参滴丸200、400、800 mg·kg^(-1)组(实验1、2、3组),每组6只。模型组、卡托普利组及实验1、2、3组大鼠背部皮下多点注射0.5 mg·mL^(-1)异丙肾上腺素注射液(3 mg·kg^(-1)),对照组大鼠背部皮下多点注射等体积的生理盐水,均每日1次,连续注射7 d;7 d后,对照组和模型组大鼠给予生理盐水灌胃(1 mL·100 g^(-1)),实验1、2、3组和卡托普利组大鼠分别给予复方丹参滴丸(200、400、800 mg·kg^(-1))及卡托普利(60 mg·kg^(-1))灌胃,每日1次,连续给药12周后,测大鼠体质量,腹腔注射100 g·L^(-1)水合氯醛1 mL麻醉大鼠,分离心脏,测心脏质量,计算心脏质量指数和心肌肥厚指数,然后取大鼠左心室心肌组织匀浆,采用酶联免疫吸附试验法测定大鼠心肌组织中脑钠肽(BNP)、血管紧张素Ⅱ(AngⅡ)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及白细胞介素-10(IL^(-1)0)水平。结果各组大鼠心脏质量指数、心肌肥厚指数、心肌组织中BNP、AngⅡ、SOD、MDA、IL-6、IL^(-1)0、TNF-α水平比较差异具有统计学意义(F=10.102、4.173、10.631、12.317、31.355、5.003、17.931、14.110、9.992,P<0.05)。模型组和实验1、2组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、MDA、IL-6、IL^(-1)0和TNF-α水平均显著高于对照组(P<0.05),SOD水平显著低于对照组(P<0.05);卡托普利组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、MDA、IL-6和IL^(-1)0水平显著高于对照组,SOD和TNF-α水平显著低于对照组(P<0.05);实验3组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、SOD、MDA、IL-6和TNF-α水平与对照组比较差异无统计学意义(P>0.05),IL^(-1)0水平显著高于对照组(P<0.05)。卡托普利组及实验1、2、3组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、MDA、IL-6、IL^(-1)0和TNF-α水平均显著低于模型组(P<0.05),SOD水平显著高于模型组(P<0.05)。实验1组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、MDA、IL-6、IL^(-1)0和TNF-α水平显著高于卡托普利组(P<0.05),SOD水平显著低于卡托普利组(P<0.05);实验2组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、SOD和MDA水平与卡托普利组比较差异无统计学意义(P>0.05),IL-6水平显著低于卡托普利组(P<0.05),IL^(-1)0和TNF-α水平显著高于卡托普利组(P<0.05);实验3组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、MDA、IL-6水平显著低于卡托普利组(P<0.05),SOD和TNF-α水平显著高于卡托普利组(P<0.05),但2组IL^(-1)0水平比较差异无统计学意义(P>0.05)。实验2、3组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、MDA、IL-6和TNF-α水平显著低于实验1组(P<0.05),SOD水平显著高于实验1组(P<0.05)。实验2组与实验1组大鼠心肌组织中IL^(-1)0水平比较差异无统计学意义(P>0.05),实验3组大鼠心肌组织中IL^(-1)0水平显著低于实验1组(P<0.05);实验3组大鼠的心脏质量指数、心肌肥厚指数及心肌组织中BNP、AngⅡ、MDA、IL-6、IL^(-1)0和TNF-α水平显著低于实验2组(P<0.05),SOD水平显著高于实验2组(P<0.05)。结论复方丹参滴丸能够提高心肌肥厚大鼠心肌的抗氧化应激能力,降低心肌炎性反应,对心肌肥厚大鼠心肌有一定的治疗作用。

Objective To investigate the effect of compound Danshen dripping pill on myocardium and myocardial oxidation index and inflammatory factors in rats with experimental myocardial hypertrophy.Methods Thirty-six male Sprague Dawley rats were randomly divided into control group,model group,captopril group,compound Danshen dropping pill200 mg·kg-1 group（experiment group 1）,compound Danshen dropping pill 400 mg·kg-1 group（experiment group 2） and compound Danshen dropping pill 800 mg·kg-1（experiment group 3）,six rats in each group.The rats in the model group,captopril group,experiment group 1,2 and 3 were performed with 0.5 mg·mL-1 isoprenaline injection（3 mg·kg-1） by multipoint subcutaneous injection;and the rats in the control group were performed with equal volume of physiological saline by multipoint subcutaneous injection;once a day for seven days.After seven days,the rats in the control group and the model group were performed with physiological saline（1 mL·100 g-1） by intragastric administration,the rats in the captopril groups were performed with captopril（60 mg·kg-1） by intragastric administration,and the rats in the experiment group 1,2 and 3 were performed with compound Danshen dropping pill（200,400 and 800 mg·kg-1 respectively） by intragastric administration;once a day for twelve weeks.Then,the body mass of rats was measured.The heart of rats was separated and the mass of the heart was measured after anesthesia by intraperitoneal injection with 1 mL chloral hydrate（100 g·L-1）,and the cardiac mass index and the myocardial hypertrophy index were calculated.The 0.5 g left ventricular myocardium was taken to prepare homogenate.The levels of brain natriuretic peptide（BNP）,angiotensin Ⅱ（Ang Ⅱ）,superoxide dismutase（SOD）,malondialdehyde（MDA）,tumor necrosis factor-α（TNF-α）,interleukin-6（IL-6） and interleukin-10（IL-10） in the cardiac muscle tissue were detected by enzyme linked immunosorbent assay.Results There were statistical significances in the cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,SOD,MDA,IL-6,IL-10,TNF-α among the groups（F=10.102,4.173,10.631,12.317,31.355,5.003,17.931,14.110,9.992;P〈0.05）.The cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,MDA,IL-6,IL-10 and TNF-α in the model group and experiment group 1 and 2 were significantly higher than those in the control group（P〈0.05）;and the SOD level was significantly lower than that in the control group（P〈0.05）.The cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,MDA,IL-6 and IL-10 in the captopril group were significantly higher than those in the control group（P〈0.05）,and the SOD and TNF-α levels were significantly lower than that in the control group（P〈0.05）.There was no significant difference in the cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,SOD,MDA,IL-6 and TNF-α between the experiment group 3 and control group（P〈0.05）.The IL-10 level in the experiment group 3 was significantly higher than that in the control group（P〈0.05）.The cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,MDA,IL-6,IL-10 and TNF-α in the captopril group and experiment group 1,2 and 3 were significantly lower than those in the model group（P〈0.05）;and the SOD level was significantly higher than that in the model group（P〈0.05）.The cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,MDA,IL-6,IL-10 and TNF-α in the experiment group 1 were significantly higher than those in the captopril group（P〈0.05）;and the SOD level was significantly lower than that in the captopril group（P〈0.05）.There was no significant difference in the cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,SOD and MDA between the experiment group 2 and captopril group（P〈0.05）.Compared with the captopril group,the IL-6 level was significantly lower,and the IL-10 and TNF-α levels were significantly higher in the experiment group2（P〈0.05）.The cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,MDA and IL-6 in the experiment group 3 were significantly lower than those in the captopril group（P〈0.05）;and the levels of SOD and TNF-α in the experiment group 3 were significantly higher than those in the captopril group（P〈0.05）;but there was no significant difference in IL-10 level between the experiment group 3 and captopril group（P〈0.05）.The cardiac mass index,myocardial hypertrophy index and the levels of BNP,Ang Ⅱ,MDA,IL-6 and TNF-α in the experiment group 2 and 3 were significantly lower than those in the experiment group 1（P〈0.05）;and the SOD level in the experiment group 2 and 3 was significantly higher than that in the experiment group 1（P〈0.05）.There was no significant difference in the IL-10 level between the experiment group 2 and experiment group 1（P〈0.05）.The IL-10 level in the experiment group 3 was significantly lower than that in the experiment group 1（P〈0.05）.The cardiac mass index,myocardial hypertrophy index and the levels of BNP,AngⅡ,MDA,IL-6,IL-10 and TNF-α in the experiment group 3 were significantly lower than those in the experiment group 2（P〈0.05）;and the SOD level in the experiment group 3 was significantly higher than that in the experiment group 2（P〈0.05）.Conclusion Compound Danshen dropping pill improve the anti-oxidative stress ability,reducing the myocardial inflammatory reaction,and have a certain therapeutic effect on myocardial hypertrophic rats.