基于网络药理学和实验验证探讨中药复方CB001对低剂量辐射防护的作用机制

doi:10.19803/j.1672-8629.20230090

摘要/Abstract

摘要： 目的基于网络药理学预测中药复方CB001对低剂量辐射（LDR）防护的潜在机制,并通过动物实验进行验证。方法基于网络药理学预测得到中药复方CB001防护LDR的可能作用靶点和通路。小鼠随机分为对照组,模型组,中药复方CB001低(1 g·kg^-1)、中(2 g·kg^-1)、高(4 g·kg^-1)给药组,对小鼠进行连续5 d的LDR,结束后处死小鼠,测定小鼠外周血白细胞、淋巴细胞总数,检测脾脏细胞凋亡,苏木素-伊红（HE）法观察各组小鼠脾脏组织形态学变化,蛋白免疫印迹法（WB）检测脾脏组织中蛋白激酶B（AKT）、磷酸化的蛋白激酶B（p-AKT）、B细胞淋巴相关X蛋白（Bax）、白细胞介素-6（IL-6）蛋白的表达。结果最终获得中药复方CB001潜在活性成分42个,79个靶点,可影响细胞周期、炎症反应调节、活性氧代谢过程,KEGG富集分析结果显示,中药复方CB001对LDR的防护主要涉及PI3K/AKT信号通路等。动物实验显示,中药复方CB001可升高小鼠外周血白细胞、淋巴细胞总数,减轻小鼠脾脏细胞凋亡,改善小鼠脾脏病理变化,促进小鼠脾脏中p-AKT蛋白表达,抑制Bax、IL-6蛋白表达。结论中药复方CB001通过减轻LDR诱导的PI3K/AKT抑制,抑制细胞凋亡,改善炎症反应,进而对LDR起到防护作用。

关键词: 中药复方CB001, 低剂量辐射, 防护, 网络药理学, PI3K/AKT信号通路, 小鼠

Abstract: Objective To predict the potential mechanism by which Chinese medicine compound CB001 protects against low dose radiation (LDR) based on network pharmacology and to verify its possible mechanism of action through animal experiments. Methods Based on prediction by network pharmacology, the possible targets and pathways of protective effect of Chinese herbal compound CB001 against LDR were obtained. The mice were randomly divided into the control group, model group and low (1 g·kg^-1), medium (2 g·kg^-1) and high (4 g·kg^-1) dose groups of Chinese medicine compound CB001. The mice were exposed to low dose irradiation for 5 consecutive days. After irradiation, the mice were killed. The total number of white blood cells and lymphocytes in the peripheral blood of the mice was measured while the apoptosis of spleen cells was detected. The morphological changes of spleen tissue in each group were observed using the hematoxylin-eosin (HE) method. The expressions of AKT, p-AKT, Bax and IL-6 were detected by Western blot. Results Finally, 42 potential active components and 79 targets of Chinese medicine compound CB001 were obtained, which could affect the cell cycle, inflammatory response regulation and reactive oxygen metabolism. The results of KEGG enrichment analysis showed that the protection of Chinese herbal compound CB001 against LDR mainly involved PI3K/AKT signaling pathway. Animal experiments showed that this compound could not only increase the total number of white blood cells and lymphocytes in peripheral blood of mice, but reduce the apoptosis of mouse spleen cells and improve the pathological changes of mouse spleens. This compound could also promote the expression levels of p-AKT protein and inhibit the expression levels of Bax and IL-6 proteins in spleens of mice. Conclusion Chinese medicine compound CB001 can protect against LDR by reducing the inhibition of PI3K/AKT signaling pathway induced by LDR, inhibiting cell apoptosis and improving inflammatory response.

Key words: Chinese medicine compound CB001, low dose radiation, protection, network pharmacology, PI3K/AKT signaling pathway, mice

中图分类号:

R979.6

梅雨, 朱越, 张慧婷, 肖成荣, 高月, 马增春. 基于网络药理学和实验验证探讨中药复方CB001对低剂量辐射防护的作用机制[J]. 中国药物警戒, 2023, 20(8): 872-879.

MEI Yu, ZHU Yue, ZHANG Huiting, XIAO Chengrong, GAO Yue, MA Zengchun. Protective mechanism of Chinese medicine compound CB001 against low dose radiation based on network pharmacology and experimental verification[J]. Chinese Journal of Pharmacovigilance, 2023, 20(8): 872-879.

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