二仙汤对去卵巢大鼠心功能和血压动态演变的干预作用

目的:探讨大鼠去卵巢后心功能、血压的演变规律及二仙汤对其的影响及机制。方法:选用健康10周龄雌性SPF级SD大鼠,随机分为假手术组、模型组、雌激素组(戊酸雌二醇,0.18 mg·kg^-1)、二仙汤组(7.5 g·kg^-1)。大鼠去卵巢后2周开始灌胃给药,1次/d,连续12周。二仙汤组及雌激素组分别给予二仙汤或戊酸雌二醇灌胃,假手术组和模型组灌胃等体积纯净水。给药4,8,12周末以无创超声心动图(UCG)及尾动脉检测技术、放免法检测心功能、血压(BP),血清雌二醇(E2)含量;给药12周末采用酶联免疫吸附测定(ELISA)检测血清内皮素-1(ET-1),血管紧张素2(AngⅡ)含量,苏木素-伊红(HE)染色、电镜技术、原位末端标记法(TUNEL)检测心肌形态学和凋亡情况。结果:与假手术组比较,给药4周末模型组射血分数(EF)减小、左室收缩末期容积(LVVols)增大(P<0.05),8周末各组心功能无显著差异,12周末模型组左室收缩末期内径(LVIDs),LVVols,左室舒张末期内径(LVIDd),左室舒张末期容积(LVVold)均显著增大(P<0.01),4,8,12周末模型组收缩压(SBP)增高(P<0.05),并呈不断升高趋势,舒张压(DBP)变化不明显,12周末模型组血清E2水平降低(P<0.05),ET-1,AngⅡ升高(P<0.01),心肌肌原纤维不规则、部分肌丝断裂,线粒体嵴紊乱、断裂或消失,细胞凋亡增多(P<0.01);与模型组比较,二仙汤组心肌收缩、舒张功能明显改善,血压降低;血清E2含量明显升高(P<0.05),血清ET-1含量明显降低(P<0.05),血清AngⅡ含量显著降低(P<0.01);心肌、线粒体形态结构改善,心肌细胞凋亡指数显著降低(P<0.01)。结论:大鼠去卵巢后出现心功能降低、血压增高等一系列病理改变,与心功能下降比较血压升高的变化出现更早,二仙汤通过调节E2,血液活性物质及心肌凋亡等途径发挥对去卵巢大鼠心功能、血压的干预作用。

Effect of Erxiantang on Cardiac Function and Blood Pressure Dynamic Evolution in Ovariectomized Rats

Objective:To investigate the evolution of cardiac function and blood pressure in ovariectomized rats and the effect and mechanism of Erxiantang.Method:Healthy 10-week-old female SPF SD rats were randomly divided into sham operation group,model group,estrogen group(estradiol valerate,0.18 mg·kg^-1)and Erxiantang group(7.5 g·kg^-1).The rats were intragastrically administered 2 weeks after ovariectomy,once a day for 12 weeks.Sham operation groups and model groups were given equal volumes of purified water.At the 4th week,8th week,and 12 thweek after administration,the cardiac function,blood pressure,and levels of estrogen(E2)in rat serum were measured by non-invasive ultrasound cardiogram(UCG),tail artery detection techniques and radioimmunoassay.The levels of endothelin-1(ET-1)and angiotensin 2(AngⅡ)in rat serum were detected by enzyme-linked immuno sorbent assay(ELISA).The cardiac morphology and apoptosis were detected by hematoxylin-eosin(HE)staining,electron microscopy and Terminaldeoxynucleoitidyl transferase mediated nick end labeling(TUNEL).Result:Compared with sham operation group,the ejection fraction(EF)decreased and the left ventricular end systolic volume(LVVols)increased in the model group at 4th week after administration(P<0.05).There was no significant difference in cardiac function between the groups at 8 thweek.The left ventricular end diastolic diameter(LVIDs),LVVols,left ventricular end diastolic diameter(LVIDd),and left ventricular end diastolic volume(LVVold)were significantly increased in the model group at 12th week(P<0.01).At the 4 thweeks,8 thweek and 12 thweek,the systolic blood pressure(SBP)of the model group increased(P<0.05)and showed an increasing trend,and the diastolic blood pressure(DBP)did not change significantly.At the 12 thweek,the levels of E2 in serum decreased(P<0.05),ET-1 and AngⅡincreased of the model group(P<0.01).The cardiac myofibrils were irregular,some myofilament was broken,and mitochondrial palsy was disordered,broken or disappeared,and cardiac apoptosis increased(P<0.01).Compared with the model group,myocardial contraction and diastolic function were significantly improved in Erxian decoction group,and blood pressure was decreased.The levels of E2 in serum was increased(P<0.05).The levels of ET-1 was decreased(P<0.05),and AngⅡin serum was significantly decreased(P<0.01).The mitochondrial morphological structure was improved and the cardiac apoptotic rate was significantly decreased(P<0.01).Conclusion:After the ovariectomy,the rats showed a series of pathological changes such as decreased heart function and increased blood pressure.Compared with the decrease of heart function,the changes of blood pressure appeared earlier.Erxiantang exerts its intervention on cardiac function and blood pressure in ovariectomized rats by regulating E2,blood active substances and cardiac apoptosis.