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J Mol Cell Cardiol. 2019 Mar;128:187-197. doi: 10.1016/j.yjmcc.2019.02.002. Epub 2019 Feb 7.
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基于PET/CT成像的山茱萸总黄酮抗心肌缺血再灌注损伤作用机制研究

Study on the mechanism of anti-MIRI action of total flavones of Fructus Chorspondiatis by PET/CT imaging.

作者信息

Zhang Guo-Jian, Wei Li-Hong, Lu Hai-Wen, Xiao Yun-Feng, Wang Wen-Rui, He Yu-Lin, Wang Xue-Mei, Tian Jia-He

机构信息

Medical School of Chinese PLA, Beijing, China.

Department of Nuclear Medicine, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China.

出版信息

Cardiovasc Diagn Ther. 2020 Aug;10(4):796-810. doi: 10.21037/cdt-20-305.

DOI:10.21037/cdt-20-305
PMID:32968635
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7487392/
Abstract

BACKGROUND

To investigate anti myocardial ischemia/reperfusion injury (MIRI) action of total flavones of Fructus Chorspondiatis (TFFC) in rats by N-ammonia micro PET/CT imaging, etc.

METHODS

Male Sprague-Dawley rats were randomly divided into 6 groups. Micro PET/CT imaging was performed before and after modeling to calculate the volume (VOI) and SUV of myocardial ischemic area. The oxidative stress index [(superoxide dismutase (SOD), malondialdehyde (MDA)] and the marker enzymes [creatine kinase (CK), lactate dehydrogenase (LDH)] of myocardial injury were detected. The pathological changes of myocardial were observed via HE staining. A MIRI model of rat cardiomyocytes in vitro was established, the damage and apoptosis of myocardial cells in each group were observed, and the apoptosis rate of cardiomyocytes was detected.

RESULTS

The imaging viscosities of the imaging agents were observed at 24 and 48 h in each group. The VOI of 24 h imaging was (6.33±2.02), (6.01±1.56) and (3.32±0.86) mm, respectively. The VOI of 48 h imaging was (3.31±1.33), (2.61±1.01) and (1.32±0.58) mm. The 72 h imaging medium and high dose group recovered, while the low dose group still saw sparseness with (1.26±0.68) mm VOI. The ischemic (SUV) gradually increased with time. Metabolism gradually recovered (F=121.82, 450.82, 435.75, P<0.05). The three doses of TFFC can eliminate free radicals and reduce the damage of myocardial injury. Amongst them, the high-dose group had a better effect on SOD, and the middle-dose group had a better effect on MDA and LDH. The low-dose group affected CK, and a significant difference was observed compared with the control group (P<0.05). After administration, the morphology of myocardial cells in each dose group was improved to some extent. Nuclear pyknosis, rupture, the apoptosis rate, etc. were significantly reduced, the number of cells increased. The high dose group showed the most obvious improvement.

CONCLUSIONS

The PET/CT imaging method can detect non-invasive, in vivo and dynamic MIRI, and can accurately evaluate the protective effect of traditional Mongolian medicine TFFC on MIRI. The Anti-MIRI of TFFC can scavenge free radicals, reduce oxidative stress damage, inhibit apoptosis, affect the activity of related enzymes.

摘要

背景

通过N-氨微PET/CT成像等方法研究广枣总黄酮(TFFC)对大鼠心肌缺血/再灌注损伤(MIRI)的作用。

方法

将雄性Sprague-Dawley大鼠随机分为6组。建模前后进行微PET/CT成像,计算心肌缺血区域的体积(VOI)和SUV。检测氧化应激指标[超氧化物歧化酶(SOD)、丙二醛(MDA)]和心肌损伤的标志物酶[肌酸激酶(CK)、乳酸脱氢酶(LDH)]。通过HE染色观察心肌的病理变化。建立大鼠心肌细胞体外MIRI模型,观察各组心肌细胞的损伤和凋亡情况,检测心肌细胞凋亡率。

结果

观察各组24 h和48 h时显像剂的成像黏度。24 h成像的VOI分别为(6.33±2.02)、(6.01±1.56)和(3.32±0.86)mm。48 h成像的VOI为(3.31±1.33)、(2.61±1.01)和(1.32±0.58)mm。72 h成像中、高剂量组恢复,低剂量组仍稀疏,VOI为(1.26±0.68)mm。缺血(SUV)随时间逐渐增加。代谢逐渐恢复(F=121.82、450.82、435.75,P<0.05)。TFFC三个剂量均可清除自由基,减轻心肌损伤。其中,高剂量组对SOD效果较好,中剂量组对MDA和LDH效果较好。低剂量组影响CK,与对照组比较差异有统计学意义(P<0.05)。给药后,各剂量组心肌细胞形态均有不同程度改善。核固缩、破裂、凋亡率等明显降低,细胞数量增加。高剂量组改善最明显。

结论

PET/CT成像方法可无创、活体、动态检测MIRI,并能准确评价传统蒙药TFFC对MIRI的保护作用。TFFC抗MIRI的作用机制可能是清除自由基、减轻氧化应激损伤、抑制凋亡、影响相关酶的活性。