中华中医药学刊

基于ATF6/GRP78通路探讨抗纤益心方对扩张型心肌病小鼠心肌细胞凋亡的影响

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常红波 ¹^,² , 王振涛 ² , 吴鸿 ¹ , 曾垂义 ² , 刘舜禹 ² , 秦楠 ²

中华中医药学刊 | 国家项目点击 2026,44(7): 45-49

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中华中医药学刊 |国家项目点击 2026 , 44 (7) : 45 -49

基于ATF6/GRP78通路探讨抗纤益心方对扩张型心肌病小鼠心肌细胞凋亡的影响

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常红波¹^,², 王振涛², 吴鸿¹, 曾垂义², 刘舜禹², 秦楠²

作者信息

^1.河南中医药大学，河南　郑州　450046

^2.河南省中医院，河南　郑州　450002

通讯作者:

王振涛（1962-），男，河南滑县人，教授，博士研究生导师，博士，研究方向：中医药防治心血管疾病的临床与基础。E-mail：13803817796@139.com。

作者简介:

常红波（1987-），男，河南开封人，副教授、主治医师，硕士研究生导师，博士，研究方向：中医药防治心血管疾病的临床与基础。

Effect of Kangxian Yixin Decoction (抗纤益心方) on Cardiomyocyte Apoptosis in Mice with Dilated Cardiomyopathy Based on ATF6/GRP78 Pathway

Hongbo CHANG¹^,², Zhentao WANG², Hong WU¹, Chuiyi ZENG², Shunyu LIU², Nan QIN²

Affiliations

^1.Henan University of Chinese Medicine, Zhengzhou 450046, Henna, China

^2.Henan Province Hospital of Traditional Chinese Medicine, Zhengzhou 450002, Henna, China

出版时间: 2026-07-10 doi: 10.13193/j.issn.1673-7717.2026.07.009

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摘要

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目的

观察抗纤益心方对扩张型心肌病（DCM）小鼠心肌细胞凋亡及内质网跨膜蛋白转录激活因子6（ATF6）、分子伴侣葡萄糖调节蛋白78（GRP78）、C/EBP同源蛋白（CHOP）的影响，探讨抗纤益心方调控GRP78/ATF6信号通路改善DCM心肌细胞凋亡的作用机制。

方法

实验中40只cTnT^R141W转基因DCM小鼠按照随机数字表法分为模型组、抗纤益心方高剂量（5.4 g/kg）组、抗纤益心方低剂量（2.7 g/kg）组、卡托普利（0.01 g/kg）组，每组10只，10只C57BL/6J小鼠作为正常组，药物干预8周，利用小动物超声仪评价心脏功能包括左室舒张末期内径（LVEDD）、左室收缩末期内径（LVESD）、射血分数（EF）、缩短率（FS），HE染色心肌组织病理形态，透射电子显微镜检测内质网超微结构，TUNEL法检测心肌组织凋亡，免疫组化法（IHC）检测心肌组织ATF6、GRP78表达，实时荧光定量聚合酶链式反应（Real-time PCR）检测心肌GRP78、ATF6、CHOP mRNA表达，蛋白免疫印迹法（Western blot）检测心肌GRP78、ATF6、CHOP、B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）蛋白表达。

结果

与正常组比较，模型组小鼠LVESD和LVEDD升高、FS和EF降低（P<0.05），心肌损伤，细胞凋亡数明显增加（P<0.01），内质网结构受损、肿大；免疫组化GRP78、ATF6表达均增加（P<0.01）；GRP78、ATF6、CHOP mRNA表达均增加（P<0.01）；GRP78、ATF6、CHOP、Bax蛋白表达均增加（P<0.01），抗凋亡因子Bcl-2蛋白表达降低（P<0.01）；与模型组比较，抗纤益心方高、低剂量组LVESD和LVEDD降低、FS和EF增加（P<0.05），心肌损伤减轻，细胞凋亡减少（P<0.05，P<0.01），内质网损伤及肿大减轻，免疫组化GRP78、ATF6表达均降低（P<0.05，P<0.01）；GRP78、ATF6、CHOP mRNA表达均降低（P<0.05，P<0.01）；GRP78、ATF6、CHOP、Bax蛋白表达均降低（P<0.05，P<0.01），抗凋亡因子Bcl-2蛋白表达增加（P<0.05，P<0.01）。

结论

抗纤益心方能够抑制DCM小鼠心肌细胞凋亡，提高心脏功能，其作用机制可能与抑制内质网应激、下调ATF6/GRP78信号通路有关。

关键词

抗纤益心方 / 扩张型心肌病 / 心肌细胞凋亡 / 内质网应激 / ATF6/GRP78信号通路

Abstract

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Objective

To observe the effects of Kangxian Yixin Decoction (抗纤益心方, KYD) on cardiomyocyte apoptosis and endoplasmic reticulum stress-related factors glucose regulated protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) in mice with dilated cardiomyopathy (DCM), and to explore the mechanism of KYD regulating GRP78/ATF6 signaling pathway to improve the apoptosis of DCM cardiomyocytes.

Methods

According to the random number table method, 40 cTnT^R141W transgenic DCM mice were divided into model group, KYD high and low dose (5.4 g/kg, 2.7 g/kg) groups and captopril (0.01 g/kg) group, with 10 mice in each group. Another C57BL/6J mice were set up as the normal group. Left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), ejection fraction (EF) and reduction rate (FS) were detected by ultrasonography in small animals. Myocardial pathological morphology was observed by HE staining, endoplasmic reticulum ultrastructure was observed by electron microscopy, and myocardial apoptosis was detected by TUNEL method. The expression levels of GRP78 and ATF6 in myocardial tissue of mice were detected by immunohistochemistry (IHC) method. The mRNA and protein expressions of GRP78, ATF6, CHOP, Bax and Bcl-2 were detected by Real-time PCR and Western blot, respectively.

Results

Compared with those in the normal group, the levels of LVESD and LVEDD were increased in the model group, the levels of FS and EF were decreased (P<0.05), myocardial pathological injury and apoptosis number increased (P<0.01), endoplasmic reticulum structure was damaged and enlarged. The expressions of GRP78 and ATF6 were increased by IHC (P<0.05). The mRNA expressions of GRP78, ATF6 and CHOP were increased (P<0.05). The expressions of GRP78, ATF6, CHOP and Bax were increased, while the expression of anti-apoptotic factor Bcl-2 was decreased (P<0.05). Compared with those in the model group, the levels of LVESD and LVEDD were decreased, the levels of FS and EF were increased (P<0.05), myocardial injury was alleviated, the apoptosis was decreased, the endoplasmic reticulum was damaged and enlarged, and IHC results showed that the expressions of GRP78 and ATF6 were decreased (P<0.05、P<0.01) in the KYD groups. The mRNA expressions of GRP78, ATF6 and CHOP were decreased (P<0.05, P<0.01). The expressions of GRP78, ATF6, CHOP and Bax were decreased (P<0.05, P<0.01), while the expressions of anti-apoptotic factor Bcl-2 were increased (P<0.05, P<0.01).

Conclusion

KYD can inhibit DCM cardiomyocyte apoptosis and improve the cardiac function in mice, and its mechanism may be related to inhibiting endoplasmic reticulum stress and down-regulating ATF6/GRP78 signaling pathway.

Key words

Kangxian Yixin Decoction (抗纤益心方) / dilated cardiomyopathy / cardiomyocyte apoptosis / endoplasmic reticulum stress / ATF6/GRP78 signaling pathway

引用本文

常红波, 王振涛, 吴鸿, 曾垂义, 刘舜禹, 秦楠. 基于ATF6/GRP78通路探讨抗纤益心方对扩张型心肌病小鼠心肌细胞凋亡的影响. 中华中医药学刊, 2026 , 44 (7) : 45 -49 . DOI: 10.13193/j.issn.1673-7717.2026.07.009

Hongbo CHANG, Zhentao WANG, Hong WU, Chuiyi ZENG, Shunyu LIU, Nan QIN. Effect of Kangxian Yixin Decoction (抗纤益心方) on Cardiomyocyte Apoptosis in Mice with Dilated Cardiomyopathy Based on ATF6/GRP78 Pathway[J]. Chinese Archives of Traditional Chinese Medicine, 2026 , 44 (7) : 45 -49 . DOI: 10.13193/j.issn.1673-7717.2026.07.009

基金

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国家自然科学基金青年科学基金项目(82205082)
河南省科技研发计划项目（优势学科培育类）(232301420066; 252301420073)
河南省高等学校重点科研项目(24A360001)
河南省中医药科研专项联合共建项目(2025LHZX2056)
河南省中医药科学研究专项(2023ZY2086)

参考文献

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2026年第44卷第7期

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doi: 10.13193/j.issn.1673-7717.2026.07.009

首发时间：2026-10-20
出版时间：2026-07-10

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基金

国家自然科学基金青年科学基金项目(82205082)

河南省科技研发计划项目（优势学科培育类）(232301420066; 252301420073)

河南省高等学校重点科研项目(24A360001)

河南省中医药科研专项联合共建项目(2025LHZX2056)

河南省中医药科学研究专项(2023ZY2086)

作者信息

^1.河南中医药大学，河南　郑州　450046

^2.河南省中医院，河南　郑州　450002

通讯作者:

王振涛（1962-），男，河南滑县人，教授，博士研究生导师，博士，研究方向：中医药防治心血管疾病的临床与基础。E-mail：13803817796@139.com。

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https://castjournals.cast.org.cn/joweb/zhzyyxk/CN/10.13193/j.issn.1673-7717.2026.07.009

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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