1. 河南中医药大学第二临床医学院
2. 河南省中医院
纸质出版:2021
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[1]刘舜禹,李巧稚,芮浩淼,王振涛,常红波,郭宗耀,吴鸿.抗纤益心方对扩张型心肌病模型大鼠心肌纤维化相关因子及心肌组织β-catenin/PPARγ信号通路的影响[J].中医杂志,2021,62(03):259-265.
LIU Shunyu, LI Qiaozhi, RUI Haomiao, et al. Effects of Kangxian Yixin Recipe (抗纤益心方) on Myocardial Fibrosis Related Factors and β-catenin/PPARγ Signaling Pathway in Myocardial Tissue of Dilated Cardiomyopathy Model Rats[J]. Journal of Traditional Chinese Medicine2021, 62(3): 259-265.
[1]刘舜禹,李巧稚,芮浩淼,王振涛,常红波,郭宗耀,吴鸿.抗纤益心方对扩张型心肌病模型大鼠心肌纤维化相关因子及心肌组织β-catenin/PPARγ信号通路的影响[J].中医杂志,2021,62(03):259-265. DOI: 10.13288/j.11-2166/r.2021.03.015.
LIU Shunyu, LI Qiaozhi, RUI Haomiao, et al. Effects of Kangxian Yixin Recipe (抗纤益心方) on Myocardial Fibrosis Related Factors and β-catenin/PPARγ Signaling Pathway in Myocardial Tissue of Dilated Cardiomyopathy Model Rats[J]. Journal of Traditional Chinese Medicine2021, 62(3): 259-265. DOI: 10.13288/j.11-2166/r.2021.03.015.
目的探讨抗纤益心方治疗扩张型心肌病(DCM)心肌纤维化的可能作用机制。方法 100只Wistar大鼠随机分为正常组8只及造模组92只。造模组大鼠采用自主饮用呋喃唑酮水溶液法制备DCM大鼠模型
将造模成功的40只大鼠随机分为模型组、卡托普利组及抗纤益心方低、中、高剂量组
每组8只。抗纤益心方低、中、高剂量组分别给予抗纤益心方0.9、1.8、3.6g/(kg·d)灌胃
卡托普利组给予卡托普利片10.13mg/(kg·d)灌胃
正常组与模型组给予生理盐水5.3ml/(kg·d)灌胃。干预4周后检测各组大鼠左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左心室射血分数(LVEF)和左室轴缩短率(LVFS)
观察大鼠心肌组织病理变化情况
检测纤维化相关指标α平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白表达
β连环蛋白(β-catenin)、过氧化物酶体增殖剂激活受体γ(PPARγ)蛋白及mRNA表达。结果与正常组比较
模型组大鼠LVEDD、LVESD升高
LVEF、LVFS降低(P<0.05)
心肌病理损害加重
心肌组织α-SMA、Ⅰ型胶原蛋白、β-catenin蛋白及mRNA表达升高
PPARγ蛋白及mRNA表达降低(P<0.05)。与模型组比较
抗纤益心方中、高剂量组及卡托普利组大鼠LVEDD、LVESD降低
LVEF、LVFS升高(P<0.05)
心肌病理纤维化程度减轻
心肌组织α-SMA和Ⅰ型胶原蛋白表达降低(P<0.05);抗纤益心方中、高剂量组大鼠心肌组织β-catenin蛋白及mRNA表达降低
PPARγ蛋白及mRNA表达升高(P<0.05)。与卡托普利组比较
抗纤益心方中、高剂量组大鼠心肌组织β-catenin蛋白及mRNA表达降低(P<0.05)
LVEDD、LVESD、LVEF、LVFS、Ⅰ型胶原蛋白、PPARγ蛋白及mRNA表达差异无统计学意义(P>0.05)。与抗纤益心方低剂量组比较
抗纤益心方中、高剂量组LVEDD、LVESD降低
LVEF、LVFS、PPARγmRNA表达升高
抗纤益心方高剂量组Ⅰ型胶原蛋白表达降低(P<0.05)
抗纤益心方中、高剂量组组间各指标比较差异无统计学意义(P>0.05)。结论抗纤益心方能够有效改善DCM大鼠心功能
抑制心室重构及心肌纤维化发展
以中、高剂量效果更好
其作用机制可能与调控心肌组织β-catenin/PPARγ通路有关。
Objectives To investigate the effects and possible mechanism of Kangxian Yixin Recipe(抗纤益心方) on myocardial fibrosis in dilated cardiomyopathy(DCM). Methods Totally 100 rats were randomly divided into normal group(8 rats) and model making group(92 rats). The DCM model was established by drinking the solution of furazolidone aqueous autonomously. Forty successful modeling rats were further randomly divided into model group
captopril group
Kangxian Yixin Recipe low
medium and high dose groups
with eight rats in each group. Kangxian Yixin Recipe low
medium and high dose group rats were administered with Kangxian Yixin Recipe by gavage at a dose of 0.9 g/(kg·d)
1.8 g/(kg·d)
and 3.6 g/(kg·d)
respectively; captopril 10.13 mg/(kg·d) by gavage was given to captopril group
while normal saline 5.3 ml/(kg·d) by gavage was given to the normal group and model group. After four weeks
the left ventricular end-diastolic diameter(LVEDD)
left ventricular end-systolic diameter(LVESD)
left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS) levels were detected; the pathological changes of myocardial tissues was assessed; the protein and mRNA expression of alpha-smooth muscle actin(α-SMA)
type I collagen
β-catenin and peroxisome proliferators-activated receptor γ(PPARγ) were determined. Results Compared to the normal group
LVEDD and LVESD levels in the model group significantly increased
while LVEF and LVFS levels decreased(P<0.05); the myocardial pathological damage was aggravating; the protein and mRNA expression of α-SMA
type I collagen and β-catenin increased
while the expression of PPARγ protein and mRNA decreased(P<0.05). Compared to the model group
the LVEDD and LVESD levels were reduced
the LVEF and LVFS levels increased; the degree of myocardial pathologic fibrosis and the protein expression of α-SMA and type I collagen decreased in Kangxian Yixin Recipe medium and high dose groups and captopril group(P<0.05); the expression of β-catenin protein and mRNA significantly decreased
while the expression of PPARγ protein and mRNA increased in Kangxian Yixin Recipe medium and high dose groups(P<0.05). Compared to captopril group
Kangxian Yixin Recipe medium and high dose groups had lower expression levels of β-catenin protein and mRNA(P<0.05)
while no significant differences were found in LVEDD
LVESD
LVED
LVFS levels
and the protein and mRNA expression of type I collagen and PPARγ(P>0.05). Compared to Kang-xian Yixin Recipe low dose group
there were lower LVEDD and LVESD levels
higher LVEF
LVFS levels and PPARγ mRNA expression in the medium and high dose groups
as well as lower expression of type I collagen protein in the high dose group(P<0.05). The comparison between Kangxian Yixin Recipe medium dose and high dose group was not significantly different in all indicators(P>0.05). Conclusion Kangxian Yixin Recipe can effectively improve the cardiac function of DCM rats
and inhibit ventricular remodeling and myocardial fibrosis; and the effect is better with medium and high doses. The mechanism may be related to the regulation of β-catenin/PPARγ pathway expression.
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