天香丹胶囊调控雌激素核效应抗心肌缺血作用研究  

Function of Tianxiangdan capsule on regulating estrogen nuclear effect and anti myocardial ischemia

作　　者：杜古加·嘎尔玛 姜林 王慧敏 吉钊 Dugujia Gaerma;JIANG Lin;WANG Huimin;JI Zhao(The Fourth College of Clinical Medicine,Xinjiang Medical University,Urumqi 830000,China;State Key Laboratory of Pathogenesis,Preven-tion and Treatment of High Incidence Diseases in Central Asia,Urumqi 830000,China;Xinjiang Key Laboratory of Traditional Chinese Medi-cine Processing,Urumqi 830000,China)

机构地区：[1]新疆医科大学第四临床医学院,乌鲁木齐830000 [2]省部共建中亚高发病成因与防治国家重点实验室,乌鲁木齐830000 [3]新疆中药炮制研究重点实验室,乌鲁木齐830000

出　　处：《新疆医科大学学报》2022年第4期444-449,共6页Journal of Xinjiang Medical University

基　　金：国家自然科学基金(81960699);省部共建中亚高发病成因与防治国家重点实验室开放课题资助项目(SKL-HIDCA-2020-8)。

摘　　要：目的研究天香丹胶囊调控雌激素核效应抗心肌缺血作用的机制。方法建立去卵巢心肌缺血再灌注大鼠双模型,取SD雌性大鼠70只(200±50)g,随机分为空白组、去卵巢组、去卵巢缺血再灌注组、雌二醇干预组(E_(2),0.8×10^(-3)g·kg^(-1)·d^(-1)),天香丹干预高、中、低剂量组(天香丹胶囊,0.8×10^(-3)、0.6×10^(-3)、0.2×10^(-3)g·kg^(-1)·d^(-1)),建立去卵巢大鼠模型,每组每天给药1次,灌胃60 d,可逆性结扎大鼠心脏左前降支使心肌缺血30 min,再灌注180 min。实验过程中心电图实时监测,记录各组大鼠的Ⅱ导联心电图;检测血清中雌激素和心肌肌钙蛋白Ⅰ(cTnⅠ)水平;伊文氏蓝-2,3,5-氯化三苯基四氮唑(TTC)双染色法测定心脏梗死面积;HE染色观察心肌组织形态;Western blot分析心肌组织细胞核中雌激素受体α(ERα)、热休克蛋白70(HSP70)、BCL2-Associated X蛋白(Bax)、B细胞淋巴瘤-2基因(Bcl-2)蛋白的表达。结果天香丹干预60 d后,与去卵巢缺血再灌注组比较,雌二醇干预组和天香丹高、中、低干预组雌激素水平显著升高,差异有统计学意义(P<0.05);与去卵巢缺血再灌注组比较,雌二醇干预组和天香丹干预组雌激素水平显著升高(P<0.05),而cTnⅠ水平降低(P<0.05),心肌梗死面积减小,HE染色心脏组织呈现出不同程度的改善,此外,雌二醇干预组和天香丹干预组心肌组织细胞核蛋白中ERα、HSP70、Bcl-2、Bcl-2/Bax蛋白的表达显著高于缺血再灌注模型组,差异有统计学意义(P<0.05),Bax蛋白的表达显著低于缺血再灌注模型组,差异有统计学意义(P<0.05)。结论天香丹胶囊调控雌激素核效应可通过激活雌激素核受体α和增加HSP70的表达,从而抑制细胞凋亡发挥抗心肌缺血作用。Objective To explore the mechanism of Tianxiangdan capsule regulating estrogen nuclear effect and anti myocardial ischemia.Methods A double model of myocardial ischemia-reperfusion in ovariectomized rats was estab⁃lished.Seventy female SD rats weighing(200±50)g were randomly divided into blank group,ovariectomized group,ovari⁃ectomized ischemia-reperfusion group and estradiol intervention group(E_(2),0.8×10^(-3)g·kg^(-1)·d^(-1)),Tianxiangdan intervention high,medium and low dose groups(Tianxiangdan capsule,0.8×10^(-3)、0.6×10^(-3)、0.2×10^(-3)g·kg^(-1)·d^(-1)).After establishing the ovariectomized rat model,each group was given once a day lasting 60 days.Reversible ligation of the left anterior descending branch of the rat heart caused myocardial ischemia for 30 minutes and reperfusion for 180 minutes.During the experiment,the electrocardiogram(ECG)was monitored in real time,and the Ⅱ lead ECG of rats in each group was recorded.The contents of estrogen and troponin Ⅰ in serum were detected.Evans blue-2,3,5-triphenyltetrazolium chloride(TTC)double staining method was used to determine the infarct size of heart.HE staining was used to ob⁃serve the morphology of myocardial tissue.Western blot analysis of Expression of estrogen receptors in myocardial nucleiα(ERα)heat shock protein 70(HSP70),BCL2 associated X protein(Bax),B-cell lymphoma-2 gene(Bcl-2)protein was analyzed through Western blot.Results After 60 days of Tianxiangdan intervention,compared with ovariectomized ischemia-reperfusion group,the estrogen level in estradiol intervention group and Tianxiangdan high,medium and low dose intervention groups increased significantly(P<0.05);compared with ovariectomized ischemia-reperfusion group,estrogen level in estradiol intervention group and Tianxiangdan intervention group increased significantly(P<0.05),while cTnⅠ content decreased(P<0.05);myocardial infarction area decreased,and HE staining of heart tissue showed different degrees of improvement.The expression of ERα,HSP70,Bcl-2 and Bcl-

关 键 词：天香丹胶囊 心肌缺血再灌注 雌激素核效应 凋亡 抗心肌缺血 

分 类 号：R284.1[医药卫生—中药学] R965[医药卫生—中医学]