中国临床药理学杂志

丹参酮ⅡA调控PI3K/AKT/mTOR通路对放射性心脏损伤作用及机制研究

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舒艳彪 ¹^,² , 王刚 ³ , 李燕玲 ¹^,² , 王博雯 ¹^,² , 谢萍 ¹^,²

中国临床药理学杂志 | 临床与基础桥接研究 2026,42(1): 72-80

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中国临床药理学杂志 |临床与基础桥接研究 2026 , 42 (1) : 72 -80

丹参酮ⅡA调控PI3K/AKT/mTOR通路对放射性心脏损伤作用及机制研究

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舒艳彪¹^,², 王刚³, 李燕玲¹^,², 王博雯¹^,², 谢萍¹^,²

作者信息

^1.甘肃中医药大学第一临床医学院，甘肃兰州 730000

^2.甘肃省人民医院心内一科，甘肃兰州 730000

^3.兰州大学第一临床医学院，甘肃兰州 730000

通讯作者:

谢萍，教授，博士生导师 MP: 13919761522 E-mail: pingxie66@163.com

作者简介:

舒艳彪（1998-），男，主治医师，主要从事肿瘤心脏病学和心血管疾病流行病学方面的研究

Research of effects on radiation-induced cardiac injury of Tanshinone ⅡA modulating the PI3K/AKT/mTOR pathway

Yan-biao SHU¹^,², Gang WANG³, Yan-ling LI¹^,², Bo-wen WANG¹^,², Ping XIE¹^,²

Affiliations

^1.The First Clinical Medical School, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China

^2.Department of Cardiology Ⅰ, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China

^3.The First Clinical Medical School, Lanzhou University, Lanzhou 730000, Gansu Province, China

出版时间: 2026-01-17 doi: 10.13699/j.cnki.1001-6821.2026.01.012

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摘要

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目的

探讨丹参酮ⅡA（Tanshinone ⅡA）通过调控磷酸肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白（PI3K/AKT/mTOR）信号通路对放射性心损伤（RIHD）的防治作用，并基于动物及细胞实验揭示其保守机制，为临床开发靶向防治策略提供理论依据。

方法

动物实验部分将SPF大鼠和小鼠分别分为空白对照组、模型组和实验组。通过单次X射线照射（大鼠25 Gy，小鼠20 Gy）建立放射性心损伤模型。空白对照组正常喂养，模型组造模后正常喂养，实验组造模后给予连续每天腹腔注射丹参酮ⅡA磺酸钠注射液（1 mg/10 g）1周。细胞实验部分将H9C2心肌细胞分为正常细胞组、诱导损伤组和药物处理组，通过辐射构建RIHD细胞模型。正常细胞组正常培养，诱导损伤组造模后正常培养，药物处理组造模后立即给予1 μL·mL^-1丹参酮ⅡA磺酸钠。动态监测体质量变化及心肌组织病理学特征；用转录组测序对大鼠和小鼠心尖组织进行联合分析，筛选共同差异表达基因及富集通路。用细胞计数试剂盒-8（CCK-8）检测细胞活力，用乳酸脱氢酶（LDH）释放实验法评估细胞膜损伤，用实时定量聚合酶链式反应（RT-qPCR）法和蛋白质印记法（WB）检测PI3K/AKT/mTOR通路关键基因血管生成素2（ANGPT2）、细胞周期蛋白D1（CCND1）及磷酸化磷酸肌醇3-激酶（P-PI3K）和磷酸化AKT丝氨酸（P-AKT）的表达水平。

结果

动物实验显示，干预后，空白对照组、模型组和实验组大鼠的体质量分别为（434.37±8.52）、（341.61±8.73）和（410.13±10.05）g；小鼠的体质量分别为（30.97±0.89）、（26.24±0.86）和（30.96±0.87）g； AST分别为（159.92±3.83）、（171.04±2.63）和（149.63±10.55）U·L^-1；CK-MB分别为（219.00±5.83）、（455.42±32.76）和（248.36±15.25）U·L^-1；LDH分别为（677.20±21.22）、（864.63±6.39）和（635.77±22.72）U·L^-1；BNP分别为（29.37±6.04）、（241.69±12.75）和（134.23±13.57）pg·mL^-1；GSH分别为（160.73±4.65）、（330.38±9.41）和（116.71±11.29）U·L^-1，模型组的上述指标与空白对照组比较；丹参酮ⅡA实验组的上述指标与模型组比较，在统计学上差异均有统计学意义（均P<0.001）。在细胞实验中，转录组联合分析发现，72%的同源差异基因（大鼠624个，小鼠341个）在2种物种中表达趋势一致，京都基因与基因组百科全书（KEGG）富集分析显示ANGPT2，CCND1，THBS1，COL4A1，FN1，COL4A2主要富集于PI3K/AKT/mTOR通路（均P<0.05），PCR验证表明了趋势一致性。体外实验证实，正常细胞组、诱导损伤组和药物干预组的细胞活力百分比分别为（118.40±8.63）%、（73.10±6.12）%和（91.57±8.08）%，诱导损伤组与正常细胞组比较；药物干预组与诱导损伤组比较，在统计学上差异均有统计学意义（均P<0.001）。诱导损伤组和药物干预组的LDH释放水平分别为正常细胞组的（1.03±0.02）和（0.77±0.01）倍，药物干预组与诱导损伤组比较，在统计学上差异有统计学意义（P<0.001）。正常细胞组、诱导损伤组和药物干预组的P-PI3K相对表达水平分别为0.92±0、0.76±0.01和0.85±0.02；P-AKT相对表达水平分别为0.79±0.01、0.70±0.01和0.76±0.01，诱导损伤组与正常细胞组比较；药物干预组与诱导损伤组比较，在统计学上差异均有统计学意义（均P<0.05）。

结论

丹参酮ⅡA通过激活PI3K/AKT/mTOR信号通路，上调关键磷酸化蛋白（P-PI3K、P-AKT），降低辐射毒性，提升细胞活力，从而防治放射性心脏损伤。

关键词

丹参酮ⅡA / 放射性心损伤 / 磷酸肌醇3-激酶/蛋白激酶B/雷帕霉素靶蛋白通路 / 转录组

Abstract

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Objective

To investigate the preventive and therapeutic effects of Tanshinone ⅡA on radiation-induced heart disease (RIHD) through the regulation of the phosphoinositide 3-kinase/AKT/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway, and to elucidate its underlying mechanisms based on animal and cellular experiments, thereby providing a theoretical foundation for developing targeted clinical prevention and treatment strategies.

Methods

In animal experiments, SPF-grade rats and mice were respectively divided into blank control group, model group and experimental group. A single dose of X-ray irradiation (25 Gy for rats, 20 Gy for mice) was administered to establish the RIHD model. The blank control group received normal feeding. The model group received normal feeding after modeling. The experimental group received daily intraperitoneal injections of Tanshinone ⅡA sulfonate sodium injection (1 mg/10 g body weight) for one week following modeling. In cell experiments, H9C2 cardiomyocytes were divided into normal cell group, injury-induced group and a drug-treated group. A radiation-induced RIHD cell model was established. The normal cell group was cultured under standard conditions. The injury-induced group was cultured normally after modeling. The drug-treated group was administered Tanshinone ⅡA sulfonate sodium (1μL·mL^-1 culture medium) immediately after modeling. Body weight changes and myocardial histopathological characteristics were dynamically monitored. Transcriptome sequencing was performed on cardiac apex tissues from both rats and mice for joint analysis, aiming to screen for common differentially expressed genes and enriched pathways. Cell viability was assessed using the cell counting kit-8 (CCK-8) assay. Cell membrane damage was evaluated by the lactate dehydrogenase (LDH) release assay. The expression levels of key genes in PI3K/AKT/mTOR pathway, including angiopoietin-2 (ANGPT2) and cyclin D1 (CCND1), as well as the protein levels of phosphorylated phosphoinositide 3-kinase (P-PI3K) and phosphorylated AKT serine/threonine kinase (P-AKT) were detected using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively.

Results

Animal experiments showed that after the intervention, the body weights of rats in the blank control group, model group and experimental group were (434.37±8.52), (341.61±8.73) and (410.13±10.05) g, respectively; the body weights of mice were (30.97±0.89), (26.24±0.86) and (30.96±0.87) g, respectively; AST levels were (159.92±3.83), (171.04±2.63) and (149.63±10.55) U·L^-1, respectively; CK-MB levels were (219.00±5.83),(455.42±32.76) and (248.36±15.25) U·L^-1, respectively; LDH levels were (677.20±21.22),(864.63±6.39) and (635.77±22.72) U·L^-1, respectively; BNP levels were (29.37±6.04),(241.69±12.75) and (134.23±13.57) pg·mL^-1, respectively; GSH levels were (160.73±4.65), (330.38±9.41) and (116.71±11.29) U·L^-1, respectively. All the aforementioned indicators in model group showed statistically significant differences compared to blank control group, and all indicators in the experimental group showed statistically significant differences compared to model group (all P<0.001). In the cell experiments, joint transcriptome analysis revealed that 72% of homologous differentially expressed genes (624 in rats, 341 in mice) exhibited consistent expression trends in both species. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis indicated that ANGPT2, CCND1, THBS1, COL4A1, FN1 and COL4A2 were primarily enriched in the PI3K/AKT/mTOR pathway (all P<0.05), and PCR validation confirmed this consistent trend. In vitro experiments confirmed that the cell viabilities in normal cell group, injury-induced group and drug-treated group were (118.40±8.63)%, (73.10±6.12)% and (91.57±8.08)%, respectively. The differences between injury-induced group and normal cell group, as well as between drug-treated group and injury-induced group, were statistically significant (both P<0.001). The LDH release levels in injury-induced group and drug-treated group were (1.03±0.02) and (0.77±0.01)-fold that of normal cell group, respectively. The difference between the drug-treated group and the injury-induced group was statistically significant (P<0.001). The relative expression levels of P-PI3K in normal cell group, injury-induced group and drug-treated group were 0.92±0, 0.76±0.01 and 0.85±0.02, respectively; the relative expression levels of P-AKT were 0.79±0.01, 0.70±0.01 and 0.76±0.01, respectively. The differences between the injury-induced group and the normal cell group, as well as between the drug-treated group and the injury-induced group were statistically significant (all P<0.05).

Conclusion

Tanshinone ⅡA mitigates radiation-induced cardiac injury by activating the PI3K/AKT/mTOR signaling pathway, upregulating key phosphorylated proteins (p-PI3K and p-AKT), reducing radiation toxicity and enhancing cellular viability.

Key words

Tanshinone ⅡA / radiation-induced heart disease / phosphoinositide 3-kinase/AKT/mechanistic target of rapamycin signaling pathway / transcriptome

引用本文

舒艳彪, 王刚, 李燕玲, 王博雯, 谢萍. 丹参酮ⅡA调控PI3K/AKT/mTOR通路对放射性心脏损伤作用及机制研究. 中国临床药理学杂志, 2026 , 42 (1) : 72 -80 . DOI: 10.13699/j.cnki.1001-6821.2026.01.012

Yan-biao SHU, Gang WANG, Yan-ling LI, Bo-wen WANG, Ping XIE. Research of effects on radiation-induced cardiac injury of Tanshinone ⅡA modulating the PI3K/AKT/mTOR pathway[J]. Chinese Journal of Clinical Pharmacology, 2026 , 42 (1) : 72 -80 . DOI: 10.13699/j.cnki.1001-6821.2026.01.012

基金

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国家自然科学基金资助项目(82460051)
甘肃省联合科研基金重大项目基金资助项目(24JRRA886)
2025年度甘肃省研究生“创新之星”项目基金资助项目(2025CXZX-949)

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2026年第42卷第1期

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文章信息

doi: 10.13699/j.cnki.1001-6821.2026.01.012

接收时间：2025-05-15
首发时间：2026-08-06
出版时间：2026-01-17

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收稿日期：2025-05-15

基金

国家自然科学基金资助项目(82460051)

甘肃省联合科研基金重大项目基金资助项目(24JRRA886)

2025年度甘肃省研究生“创新之星”项目基金资助项目(2025CXZX-949)

作者信息

^1.甘肃中医药大学第一临床医学院，甘肃兰州 730000

^2.甘肃省人民医院心内一科，甘肃兰州 730000

^3.兰州大学第一临床医学院，甘肃兰州 730000

通讯作者:

谢萍，教授，博士生导师 MP: 13919761522 E-mail: pingxie66@163.com

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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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