西洋参赤芍配伍对大鼠心肌梗死后早期心室重构心肌纤维化的影响

目的观察益气活血配伍(西洋参茎叶总皂苷+赤芍总苷)对大鼠心肌梗死后早期心室重构炎性因子和心肌纤维化的影响,并从胶原代谢方面探讨可能的作用机制。方法结扎Wistar大鼠冠状动脉前降支制备AMI模型,将90只造模成功的大鼠随机分为6组,每组15只,分别为假手术组(冠状动脉前降支仅穿线不结扎)、模型组、阳性对照组(灌胃缬沙坦7.2 mg·kg^-1·d^-1)、益气组(灌胃西洋参茎叶总皂苷162 mg·kg^-1·d^-1)、活血组(灌胃赤芍总苷54 mg·kg^-1·d^-1)和益气活血组(灌胃西洋参茎叶总皂苷162 mg·kg^-1·d^-1+赤芍总苷54mg·kg^-1·d^-1)。第2天开始灌胃给药,连续4周,假手术组和模型组灌胃等量蒸馏水。4周后取材,超声心动图检测心脏结构及心功能变化,HE染色观察心肌组织病理变化,免疫组织化学染色法检测缺血心肌Ⅰ、Ⅲ型胶原蛋白的表达。放射性免疫法检测血清心肌损伤标记物B型脑钠尿肽(BNP)、肌钙蛋白T(cTnT),炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β),纤维化指标层连蛋白(LA)、透明质酸(HA)、Ⅲ型前胶原氨基末端肽(PⅢNP)的含量。结果与模型组比较:(1)益气活血组大鼠心肌细胞炎性浸润减少,心肌纤维间隙水肿和心肌纤维细胞坏死变性明显减轻;(2)阳性对照组、活血组和益气活血组大鼠左室舒张末期内径(LVDd)均显著降低,左室射血分数(LVEF)均显著升高(P<0.05,P<0.05),益气活血组左室收缩末期内径(LVDs)显著降低(P<0.05);(3)阳性对照组和益气活血组心肌损伤标记物血清BNP水平明显降低(P<0.05);(4)阳性对照组和益气活血组炎性因子血清TNF-α、IL-1β含量显著降低(P<0.05,P<0.01);(5)益气活血组纤维化指标血清LA、HA、PⅢNP含量明显降低(P<0.05);(6)阳性对照组和益气活血组损伤心肌Ⅰ、Ⅲ型胶原蛋白表达明显降低(P<0.05,P<0.01)。结论益气活血配伍可以减轻心梗后心肌纤维化过程中的炎性反应,减少损伤心肌纤维化因子的释放及胶原的堆积从而达到减轻心室重构改善心功能的作用。

Effect of The Compatibility of Panacis Quinquefolii Radix and Peoniae Radix Rubra on Myocardial Fibrosis during Prophase Ventricular Remodeling after Acute Myocardial Infarction(AMI) in Rats

Objective To investigate the effect of the compatibility of supplementing qi and activating bloodcirculation(Panacis quinquefolii radix and Peoniae radix rubra) on inflammatory factor and myocardial fibrosisduring prophase ventricular remodeling(VR) after acute myocardial infarction(AMI) in rats and explore thepossible mechanism about collagen metabolism. Methods The AMI model was established by ligating the left anteriordescending coronary artery of Wistar rat to induce myocardial infarction. Ninety Wistar rats with model establishmentwere randomly divided into 6 groups, 15 rats in each group, including Sham group(the suture was penetratedaround the left anterior descending coronary artery,but not tied),model group,positive control group(PC) of which Valsartan was administered,supplementing qi(SQ) group of which Panas quinquefolium saponin was given,activating blood circulation(ABC) group of which total paeony glycosides was given, supplementing qi andactivating blood circulation(SQABC) group of which both Panas quinquefolium saponin and total paeony glycosideswere given. All of the medicine were given by gavage, both Sham group and model group were administered ofequivalent distilled water. After continuous intragastric administration of 4 weeks, ultrasonic cardiography wasconducted to examine the morphologic change and heart function. HE staining was used to observe the myocardialpathological change. Serum levels of B-type natriuretic peptide(BNP),cardiac troponin T(cTnT),inflammationfactors of tumor necrosis factor-alpha(TNF-α), interleukin-1β(IL-1β), myocardial fibrosis factors laminin(LN),hexadecenoic acid(HA),type Ⅲ procollagen(PⅢNP) were tested by radioimmunoassay method. Results Compared with model group:(1) Myocardial pathological changes of inflammatory infiltration in cardiac myocyte,edema in cardiac muscle fiber interspace and necrosis in myocardial fibrocyte obviously attenuated in SQABC group.(2) Ultrasonic cardiography detection showed that in PC group,ABC group,and SQABC group,1 eft ventricularend-diastole dimension reduced significantly, while left ventricular ejection fraction increased significantly(P<0.05, P<0.05). Left ventricular end-systole dimension reduced significantly in SQABC group(P<0.05).(3)The serum level of myocardial damage marker BNP obviously deceased in PC and SQABC group(P<0.05).(4)Serum levels of inflammation factors of TNF-α,IL-1β decreased significantly in PC and SQABC group(P<0.05,P<0.01);(5) Serum levels of myocardial fibrosis factors LN,HA,PⅢNP decreased significantly in SQABC group(P<0.05);(6) The myocardium protein expression of collagen Ⅰ and collagen Ⅲ decreased significantly in PCgroup and SQABC group(P<0.05, P<0.01). Conclusion The compatibility of supplementing qi and activatingblood circulation can alleviate the VR and improve heart function by alleviating the inflammation reaction in theprocess of myocardial fibrosis after AMI and reducing the release of myocardial fibrosis factors and accumulation ofcollagen.