| 尹凤敏,蒲超元,冉涛,等.淫羊藿苷对辐射所致小鼠心脏损伤的保护作用[J].中华放射医学与防护杂志,2025,45(2):83-90.Yin Fengmin,Pu Chaoyuan,Ran Tao,et al.Protective effects of icariin against radiation-induced cardiac disease in mice[J].Chin J Radiol Med Prot,2025,45(2):83-90 |
| 淫羊藿苷对辐射所致小鼠心脏损伤的保护作用 |
| Protective effects of icariin against radiation-induced cardiac disease in mice |
| 投稿时间：2024-06-01 |
| DOI：10.3760/cma.j.cn112271-20240601-00208 |
| 中文关键词: 淫羊藿苷 辐射性心脏损伤 辐射 心脏保护 |
| 英文关键词:Icariin Radiation-induced cardiac disease Radiation Cardioprotection |
| 基金项目:国家自然科学基金(82160756);贵州省中医药管理局中医药、民族医药科学技术研究专项课题(QZYY-2024-021);贵州省卫生健康委科学技术基金项目(2024GZWJKJXM1315) |
| 作者 | 单位 | E-mail | | 尹凤敏 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 蒲超元 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 冉涛 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 苏紫璇 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 吴梦嘉 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 张雷 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 罗欣怡 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 刘其林 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 陈言 | 遵义医科大学附属医院肿瘤科, 遵义 563000 | | | 龚其海 | 遵义医科大学基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室, 遵义 563000
遵义医科大学药学院, 遵义 563000 | | | 胡威 | 遵义医科大学附属医院早期临床研究病房, 遵义 563000 | huwei@zmu.edu.cn |
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| 中文摘要: |
| 目的 探讨淫羊藿苷(ICA)对C57BL/6小鼠辐射所致心脏损伤的保护作用。方法 将48只6~8周龄C57BL/6J雌性小鼠随机数表法分为对照(CON)组、照射(IR) 组和照射联合淫羊藿苷(IR+ICA)组, 每组16只。IR组和IR+ICA组接受单次30 Gy心脏照射, 对照组不照射。IR+ICA组在照射前2周开始灌胃ICA(70 mg·kg-1·d-1)至实验结束, 对照组和IR组予相同体积0.5%羧甲基纤维素钠溶剂灌胃, 实验期间监测小鼠精神状态、进食量、体重及存活率;照射2周后, 采集小鼠静脉血, 分离血清进行肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白(cTnT/TNNT2)的酶联免疫吸附检测。于照射后12周, 心脏超声评估各组小鼠心功能, 麻醉后处死小鼠, 进行HE、Masson染色评估心肌组织病理学改变及纤维化程度, 并计算心肌胶原容积分数(CVF)。实时反转录聚合酶链反应检测心脏组织中脑钠肽(BNP)、转化生长因子β(TGF-β) 及白细胞介素6(IL-6)基因表达差异。用蛋白质印迹法检测凋亡、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/AKT)通路相关蛋白。Kaplan-Meier法绘制生存曲线, Log-rank检验比较各组小鼠的生存差异。结果 IR组小鼠照射后精神萎靡、食量和活动量下降, IR+ICA组改善明显。IR组照后2周, CK-MB和cTnT水平显著升高(t = 5.28、8.89, P < 0.01)。12周后, IR组小鼠体重下降(t = 2.47, P < 0.05), 存活率降低(HR = 8.25, 95%CI:1.157~58.770, P < 0.05);心脏超声显示, IR组左心室射血分数(EF)和心室短轴缩短率(FS)下降(t = 7.02、6.51, P < 0.01), 左心室舒张期末内径(LVDD)升高(t = 4.45, P < 0.05)。病理检查表明, IR组心肌水肿, 细胞排列紊乱, 纤维化增加, 胶原容积分数(CVF)值升高。IR组BNP、TGF-β、IL-6基因表达显著升高(t = 4.23、6.39、4.61, P < 0.05)。照射后, IR组凋亡相关蛋白Cleaved Caspase-3和Bax表达增高(t = 6.29、9.54, P < 0.05), Bcl-2降低(t = 8.20, P < 0.001), PI3K和Akt的磷酸化水平降低(t = 6.47、3.42, P < 0.001)。上述情况在灌胃淫羊藿苷后得到部分改善, IR+ICA组体重高于IR组(t = 5.13, P < 0.001), 生存率显著高于IR组(HR = 0.121, 95%CI: 0.017~0.864, P < 0.05)。心脏彩超EF、FS高于IR组(t = 3.23、3.05, P < 0.05), LVDD降低(t = 3.02, P < 0.05)。IR+ICA组心肌水肿、细胞排列紊乱等表现较IR组改善。BNP、TGF-β、IL-6较IR组降低(t = 2.83、4.15、2.96, P < 0.05)。其凋亡相关蛋白Cleaved Caspase-3和Bax表达较IR组降低(t = 3.23、3.24, P < 0.05), Bcl-2升高(t = 5.92, P < 0.05), 恢复了PI3K和Akt的磷酸化水平(t = 2.89、8.35, P < 0.001)。结论 淫羊藿苷对IR导致的心脏损伤具有保护作用, 可能是通过上调PI3K和Akt 的磷酸化水平缓解心肌细胞凋亡。 |
| 英文摘要: |
| Objective To explore the cardioprotective effects of icariin (ICA) against radiation-induced cardiac disease (RICD) in C57BL/6 mice. Methods A total of 48 female C57BL/6J mice aged 6-8 weeks were randomly divided into three groups: the control group (CON), the irradiation group (IR), and the irradiation combined with icariin group (IR+ICA), with 16 mice in each group. The IR and IR+ICA groups received a single cardiac irradiation at a dose of 30 Gy, while the CON group received no radiation treatment. The IR+ICA group was treated with ICA (70 mg·kg-1·d-1) two weeks before irradiation until the end of the experiment through intragastric administration. In contrast, the CON and IR groups were treated with an equal volume of vehicle solution (0.5% sodium carboxymethyl cellulose, NaCMC) via intragastric administration. The mice's mental status, food intake, body weight, and survival rates were monitored during the experiment. At two weeks post-irradiation, the venous blood of the mice was collected and serum was separated for the enzyme-linked immunosorbent assays (ELISA) of creatine kinase MB isoenzyme (CK-MB) and cardiac troponin T (cTnT/TNNT2). At 12 weeks post-irradiation, the cardiac function of the mice was assessed using echocardiography. After the mice were euthanized under anesthesia, the histopathological changes and fibrosis degree of their myocardial tissues were assessed using hematoxylin and eosin (HE) and Masson's trichrome staining, followed by the calculation of collagen volume fraction (CVF). The differential gene expression of brain natriuretic peptide (BNP), transforming growth factor-β (TGF-β), and interleukin-6 (IL-6) in the cardiac tissues of the mice was detected using real-time reverse transcription-polymerase chain reaction (RT-PCR). Apoptosis-related proteins and proteins associated with the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were determined using Western blotting. The survival curves of the mice were plotted using Kaplan-Meier, and the survival differences of the mice among various groups were compared using the log-rank test. Results After irradiation, the mice in the IR group showed lethargy, as well as decreased food intake and activity, while these symptoms in the IR+ICA group were significantly alleviated. At two weeks post-irradiation, the CK-MB and cTnT levels of the IR group were significantly elevated compared with the CON group (t = 5.28, 8.89, P < 0.01). At 12 weeks post-irradiation, the mice in the IR group exhibited significantly decreased body weight (t = 2.47, P < 0.05) and decreased survival rates (HR = 8.25, 95% CI: 1.157- 58.770, P < 0.05) compared with the CON group. Echocardiography revealed that the IR group featured decreased left ventricular ejection fraction (EF), decreased fractional shortening (FS), and increased left ventricular end-diastolic diameter (LVDD) compared with the CON group (t = 7.02, 4.45, P < 0.05). Histopathological examination revealed that the IR group suffered from cardiomyocyte edema, disordered arrangement, and increased fibrosis, with an elevated CVF. The IR group exhibited significantly upregulated gene expression of BNP, TGF-β, and IL-6 in cardiac tissues compared with the CON group (t = 4.23, 6.39, 4.61, P < 0.05). After-irradiation, the IR group exhibited upregulated apoptosis-related proteins Cleaved Caspase-3 and Bax (t = 6.29, 9.54, P < 0.05), decreased Bcl-2 expression (t = 8.20, P < 0.001), and decreased phosphorylation levels of PI3K and Akt (t = 6.47, 3.42, P < 0.001). The symptoms of the mice were partially ameliorated after treatment with ICA. Specifically, the mice in the IR+ICA group exhibited higher body weight (t = 5.13, P < 0.001) and significantly higher survival rates (HR = 0.121, 95%CI: 0.017-0.864, P < 0.05) than the IR group. Compared to the IR group, the IR+ICA group showed elevated cardiac function indicators EF and FS(t = 3.23, 3.05, P < 0.05), and reduced LVDD (t = 3.02, P < 0.05). The histopathological analysis revealed mitigated edema and disordered arrangement of cardiomyocytes in the IR+ICA group. Furthermore, the IR+ICA group exhibited significantly lower BNP, TGF-β, and IL-6 expression levels than the IR group (t = 2.83, 4.15, 2.96, P < 0.05). The expression of apoptosis-related proteins Cleaved Caspase-3 and Bax was lower (t = 3.23, 3.24, P < 0.05), Bcl-2 expression was higher (t = 5.92, P < 0.001), and restored phosphorylation levels of PI3K and Akt (t = 2.89, 8.35, P < 0.001). Conclusions Icariin has protective effects against the RICD. It alleviates cardiomyocyte apoptosis possibly by upregulating the phosphorylation levels of PI3K and Akt. |
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