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中国中医科学院 中医基础理论研究所,北京 100700
[第一作者] 王昱涵,在读硕士,从事中医药防治心血管病的基础研究,E-mail:18363883517@163.com
*张治国,博士,研究员,从事中医药防治代谢性疾病的基础研究,E-mail:zzgtcm@163.com;
*陈彦静,博士,教授,从事中医药防治心血管病的基础研究,E-mail:chenyj010@163.com
收稿日期:2019-07-11,
网络出版日期:2019-10-21,
纸质出版日期:2020-02-05
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王昱涵, 姜燕华, 向丽华, 等. 二仙汤对去卵巢大鼠心功能和血压动态演变的干预作用[J]. 中国实验方剂学杂志, 2020,26(3):53-61.
Yu-han WANG, Yan-hua JIANG, Li-hua XIANG, et al. Effect of Erxiantang on Cardiac Function and Blood Pressure Dynamic Evolution in Ovariectomized Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(3): 53-61.
王昱涵, 姜燕华, 向丽华, 等. 二仙汤对去卵巢大鼠心功能和血压动态演变的干预作用[J]. 中国实验方剂学杂志, 2020,26(3):53-61. DOI: 10.13422/j.cnki.syfjx.20200339.
Yu-han WANG, Yan-hua JIANG, Li-hua XIANG, et al. Effect of Erxiantang on Cardiac Function and Blood Pressure Dynamic Evolution in Ovariectomized Rats[J]. Chinese journal of experimental traditional medical formulae, 2020, 26(3): 53-61. DOI: 10.13422/j.cnki.syfjx.20200339.
目的:
2
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:
2
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(E
2
)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:
2
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E
2
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E
2
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:
2
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E
2
,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。
Objective:
2
To investigate the evolution of cardiac function and blood pressure in ovariectomized rats and the effect and mechanism of Erxiantang.
Method:
2
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 4
th
week
8
th
week
and 12
th
week after administration
the cardiac function
blood pressure
and levels of estrogen (E
2
) 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(Ang Ⅱ) 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 Terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL).
Result:
2
Compared with sham operation group
the ejection fraction (EF) decreased and the left ventricular end systolic volume (LVVols) increased in the model group at 4
th
week after administration(
P
<
0.05). There was no significant difference in cardiac function between the groups at 8
th
week.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 12
th
week (
P
<
0.01). At the 4
th
weeks
8
th
week and 12
th
week
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
th
week
the levels of E
2
in serum decreased (
P
<
0.05)
ET-1 and Ang Ⅱ increased 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 E
2
in serum was increased (
P
<
0.05). The levels of ET-1 was decreased (
P
<
0.05)
and AngⅡ in 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:
2
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 E
2
blood active substances and cardiac apoptosis.
左宏玲 , 林守清 , 高晓黎 , 等 . 两种结合雌激素对围绝经期妇女雌激素水平及脂代谢影响多中心临床研究 [J]. 中国实用妇科与产科杂志 , 2018 , 34 ( 1 ): 84 - 88 .
L Hodson , R Banerjee , B Rial , et al . Menopausal status and abdominal obesity are significant determinants of hepatic lipid metabolism in women [J]. J Am Heart Assoc , 2015 , 4 ( 10 ): e002258 .
L Fernando , G Guzmán . Estrogen deficiency and the origin of obesity during menopause [J]. Biomed Res Int , 2014 , doi: 10.1155/2014/757461 http://dx.doi.org/10.1155/2014/757461 .
杨珺 , 罗爱月 , 王世宣 . 女性卵巢功能与心血管疾病 [J]. 中国妇幼保健 , 2015 , 30 ( 4 ): 644 - 647 .
J E Rossouw , R L Prentice , J E Manson , et al . Relationships of coronary heart disease with 27-hydroxycholesterol, low-density lipoprotein cholesterol, and menopausal hormone therapy [J]. Circulation , 2012 , 126 ( 13 ): 1577 - 1586 .
欧丽娜 , 张建军 , 王林元 , 等 . 具有雌激素样作用的补肾阳药对脂代谢的影响 [J]. 中国实验方剂学杂志 , 2013 , 19 ( 8 ): 371 - 374 .
王莹 , 杨硕 , 谢慧慧 , 等 . 二仙汤对去卵巢大鼠认知障碍的影响 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 17 ): 114 - 119 .
杨琳 , 马红 . 二仙汤妇科临床运用及实验研究进展 [J]. 辽宁中医药大学学报 , 2016 , 18 ( 100 ): 94 - 97 .
赵兰平 , 陈彦静 , 薛淑芳 , 等 . 二仙汤对去卵巢大鼠心脏电活动的影响 [J]. 中国实验方剂学杂志 , 2016 , 22 ( 5 ): 136 - 140 .
Z Z ZHANG , L H XIANG , L P ZHAO , et al . The protective effect of Er-Xian decoction against cardiac injury in menopausal rat model [J]. BMC Compl Alternative Med , 2018 , 18 ( 1 ): 245 - 255 .
蔡艳 , 叶玉妹 , 张涛 , 等 . 桂枝甘草龙骨牡蛎汤加减治疗阴虚火旺型更年期失眠疗效及对患者睡眠质量、神经递质的影响 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 9 ): 38 - 42 .
李蕊 , 白雅维 . 二维斑点追踪技术对绝经期妇女左心室收缩功能的评价 [J]. 中国医疗设备 , 2018 , 33 ( 3 ): 70 - 72,86 .
E L Kessler , M R Rivaud , M A Vos , et al . Sex-specific influence on cardiac structural remodeling and therapy in cardiovascular disease [J]. Biol Sex Differ , 2019 , 10 ( 1 ): 7 .
H WANG , J A Jessup , S Lindsey , et al . Abstract P143: activation of GPR30 attenuates diastolic dysfunction and LV remodeling in oophorectomized mRen2.Lewis rats [J]. Cardiovasc Res , 2012 , 94 ( 1 ): 96 - 104 .
杨慕坤 , 崔广霞 , 陈醒 , 等 . 去卵巢大鼠心脏结构和心肌细胞的改变 [J]. 国际妇产科学杂志 , 2014 , 41 ( 6 ): 670 - 673,713 .
叶茂 . 雌二醇对血管紧张素Ⅱ诱导去卵巢小鼠心室重构的作用研究 [D]. 福州 : 福建医科大学 , 2016 .
王文颖 . 二仙汤加减治疗更年期妇女高血压的临床研究 [D]. 济南 : 山东中医药大学 , 2015 .
张玉芬 , 王玉珍 , 赵洁 , 等 . 补肾活血汤对去卵巢大鼠心脏微血管内皮细胞形态及血清E 2 、ET、NO、PGI 2 、TXA 2 含量的影响 [J]. 现代生物医学进展 , 2014 , 14 ( 31 ): 6044 - 6049,6038 .
谢慧慧 , 王莹 , 杨硕 , 等 . 二仙汤对围绝经期大鼠心脏电生理的影响 [J]. 中国实验方剂学杂志 , 2019 , 25 ( 18 ): 43 - 48 .
伍娟娟 , 刘锐 , 尤昭玲 , 等 . 二仙汤对免疫性卵巢早衰模型小鼠形态学影响 [J]. 中华中医药学刊 , 2012 , 30 ( 7 ): 1645 - 1647,1709 .
牛小豆 , 李子健 , 张永珍 . 性别对成年小鼠心肌细胞收缩力的影响 [J]. 中国心血管杂志 , 2018 , 23 ( 2 ): 152 - 155 .
戴秋艳 . 女性冠心病与微循环障碍 [J]. 内科理论与实践 , 2017 , 12 ( 1 ): 9 - 14 .
高丽虹 , 孙爱军 . 绝经后女性卵泡刺激素与代谢综合征的关系 [J]. 生殖医学杂志 , 2018 , 27 ( 5 ): 499 - 502 .
陶仕英 , 牛建昭 , 赵丕文 , 等 . 二仙汤及其组方中药对幼年大鼠子宫作用的研究 [J]. 中国实验方剂学杂志 , 2010 , 16 ( 18 ): 118 - 121 .
陈惠珍 , 阮琴韵 . 高血压左心室舒张功能不全形态学的基础研究 [J]. 中华高血压杂志 , 2012 , 20 ( 11 ): 1028 - 1031 .
S Jovanović , A Jovanović , W K SHEN , et al . Low concentrations of 17 β -estradiol protect single cardiac cells against metabolic stress-induced Ca 2+ loading [J]. JACC , 2000 , 36 ( 3 ): 948 - 952 .
R Z Vera , V C Renee , R Hester , et al . Sex specific mechanisms of cardiac hypertrophy and heart failure [M]. American : Academic Press , 2019 : 291 - 318 .
陈明 , 陈志武 , 龙子江 , 等 . 无患子皂苷对自发性高血压大鼠Ang Ⅱ/p38MAPK通路介导的炎症反应与心肌肥厚的影响 [J]. 中国中药杂志 , 2013 , 38 ( 7 ): 1030 - 1035 .
M Y WANG , L Q JIANG , R E Monticone , et al . Proinflammation: the key to arterial aging [J]. Trends Endocrin Met , 2014 , 25 ( 2 ): 72 - 79 .
王超 , 张萍 . 高血压左心室肥厚形成机制的研究进展 [J]. 重庆医学 , 2015 , 44 ( 22 ): 3143 - 3146 .
Y H WANG , Y J LI , C T HE , et al . Mitochondrial regulation of cardiac aging [J]. Bba-Mol Basis Dis , 2019 , 1865 ( 7 ): 1853 - 1864 .
A R Wende , M K Brahma , G R Mcginnis , et al . Metabolic origins of heart failure [J]. JACC , 2017 , 2 ( 3 ): 297 - 310 .
吴庆 , 薛润青 , 徐曼 , 等 . 肥胖所致心肌重构及相关线粒体稳态失衡机制研究进展 [J]. 生理学报 , 2019 , 71 ( 2 ): 216 - 224 .
褚延鹏 , 刘婧 . 心肌线粒体对心脏舒缩功能影响的研究概况 [J]. 中国民族民间医药杂志 , 2014 , 23 ( 4 ): 16 - 17 .
古丽格娜·阿尤甫 , 唐莎 , 穆玉明 , 等 . 不同年龄段高血压病患者二尖瓣血流E/A比值与左心房及左心室重构的相关性 [J]. 心脏杂志 , 2016 , 28 ( 2 ): 185 - 188 .
S D Lee , W W Kuo , Y J Ho , et al . Cardiac Fas-dependent and mitochondria-dependent apoptosis in ovariectomized rats [J]. Maturitas , 2008 , 61 ( 3 ): 268 - 277 .
E A Morra , P L Rodrigues , I Couto , et al . Endurance training restores spatially distinct cardiac mitochondrial function and cardiac contractility in ovariectomized rats [J]. Free Radical Bio Med , 2019 ( 130 ): 174 - 188 .
王雪芬 , 吴力 . 二仙汤加味方联合贝那普利治疗女性更年期高血压疗效观察 [J]. 新中医 , 2016 , 48 ( 4 ): 117 - 118 .
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