激活红细胞2,3 <strong>-</strong>二磷酸甘油酸变位酶活性的中药组分筛选

doi:10.3724/zdxbyxb-2022-0178

浙江大学学报（医学版）

2022, Vol. 51

Issue (4): 430-437 DOI: 10.3724/zdxbyxb-2022-0178

专题报道

激活红细胞2,3 -二磷酸甘油酸变位酶活性的中药组分筛选

郭茜文^1,²,李文斌^2,*,王荣²,李加忠³,张汝学^2,*,张晓静²,王子晗^1,²

1. 甘肃中医药大学药学院，甘肃兰州 730000
2. 中国人民解放军联勤保障部队第九四〇医院药剂科全军高原医学实验室，甘肃兰州 730050
3. 兰州大学药学院，甘肃兰州 730000

Screening of activators of 2,3-diphosphoglycerate mutase from traditional Chinese herb medicines

GUO Qianwen^1,²,LI Wenbin^2,*,WANG Rong²,LI Jiazhong³,ZHANG Ruxue^2,*,ZHANG Xiaojing²,WANG Zihan^1,²

1. College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730000, China;
2. Department of Pharmacy, the 940th Hospital of Joint Logistics Support Force of Chinese People’s Liberation Army, Key Laboratory of the Plateau Medicine, Lanzhou 730050, China;
3. School of Pharmacy, Lanzhou University, Lanzhou 730000, China

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摘要：

目的：从中药组分中筛选2，3-二磷酸甘油酸（BPG）变位酶（BPGM）的激活剂，以提高红细胞的缺氧耐受性。 方法：以红细胞胞浆蛋白BPGM为受体，常用中药成分数据库为配体，经过里宾斯基五规则类药性筛选后，采取刚性对接（LibDock）和半柔性对接（CDOCKER）进行虚拟筛选；提取红细胞胞浆蛋白，验证筛选出来的化合物对红细胞胞浆中BPGM亲和力的影响；最后，体外孵育红细胞，建立红细胞缺氧模型，并验证化合物对红细胞缺氧模型中BPGM活性的影响。 结果：通过刚性对接和半柔性对接优选出与BPGM结合能前十的化合物。用这十种化合物孵育胞浆蛋白，与空白对照组比较，迷迭香酸甲酯各剂量组、二氢姜黄素大剂量组、八氢姜黄素中剂量组和阿魏酸松柏酯大剂量组可以进一步激活BPGM，从而显著增加常氧红细胞中的2，3-BPG含量（均 P<0.05）；四氢姜黄素小剂量组、橙黄胡椒酰胺大剂量和小剂量组、六氢姜黄素各剂量组和N-p-香豆酰-羟色胺中剂量组常氧红细胞2，3-BPG含量有增加的趋势（均 P>0.05）。缺氧红细胞在加入中剂量迷迭香酸甲酯、中剂量八氢姜黄素、大剂量六氢姜黄素和中剂量N-p-香豆酰-羟色胺后，2，3-BPG含量显著增加（均 P<0.05）。结论：迷迭香酸甲酯、八氢姜黄素、六氢姜黄素和 N-p-香豆酰-羟色胺可以激活BPGM从而提高缺氧红细胞中2，3-BPG含量。

关键词： 红细胞; 2，3-二磷酸甘油酸; 2，3-二磷酸甘油酸变位酶; 分子对接; 中药组分

Abstract:

Objective: To screen activators of 2,3-diphosphoglycerate (BPG) mutase (BPGM) from Chinese herb medicines, so as to improve the hypoxia tolerance of erythrocytes. Methods: BPGM was used as the receptor and Chinese medicine ingredients database was used as the ligand in the study. After Lipinski rule of five screening, LibDock and CDOCKER docking were used for virtual screening. The effect of the screened compounds on the affinity of BPGM in erythrocytes was verified. Finally, the erythrocytes were incubated in vitro to establish the erythrocyte hypoxia model, and the effect of the compound on the activity of BPGM in the erythrocyte hypoxia model was verified. Results: Ten compounds with highest binding affinity to BPGM were selected by LibDock and CDOCKER, and the cytoplasm protein was incubated with the ten compounds. Compared with blank control group, methyl rosmarinate group, dihydrocurcumin high dose group, octahydrocurcumin medium dose group and coniferyl ferulate high dose group were able to further activate the BPGM, significantly increase the levels of 2, 3-BPG in normal erythrocytes (all P<0.05); while the low dose of tetrahydrocurcumin, high dose and low dose of aurantiamide, hexahydrocurcumin and medium dose ofN- (p-coumaroyl) serotonin had a tendency to increase the contents of 2,3-BPG in normal erythrocytes (all P>0.05). In the hypoxic red blood cells, the medium dose methyl rosmarinate, medium dose octahydrocurcumin, high dose hexahydrocurcumin and medium doseN-(p-coumaroyl) serotonin could significantly increase the contents of 2,3-BPG (all P<0.05).Conclusion: The methyl rosmarinate, octahydrocurcumin, hexahydrocurcumin and N-(p-coumaroyl) serotonin could activate BPGM and increase the contents of 2,3-BPG in hypoxic erythrocytes.

Key words: Erythrocyte 2,3-Diphosphoglycerate 2,3-Diphosphoglycerate mutase Molecular docking Components of traditional Chinese medicine

收稿日期: 2022-04-18 出版日期: 2022-11-16

CLC:

R965.1

基金资助: 国家自然科学基金（82173738）

通讯作者: 李文斌,张汝学

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引用本文:

郭茜文,李文斌,王荣,李加忠,张汝学,张晓静,王子晗. 激活红细胞2,3 -二磷酸甘油酸变位酶活性的中药组分筛选[J]. 浙江大学学报（医学版）, 2022, 51(4): 430-437.

GUO Qianwen,LI Wenbin,WANG Rong,LI Jiazhong,ZHANG Ruxue,ZHANG Xiaojing,WANG Zihan. Screening of activators of 2,3-diphosphoglycerate mutase from traditional Chinese herb medicines. J Zhejiang Univ (Med Sci), 2022, 51(4): 430-437.

链接本文:

https://www.zjujournals.com/med/CN/10.3724/zdxbyxb-2022-0178 或 https://www.zjujournals.com/med/CN/Y2022/V51/I4/430

图1 去水加氢后的BPGM蛋白（PDB ID: 3NFY）结构三维图 BPGM：2,3-二磷酸甘油酸变位酶.

表1 与2，3-二磷酸甘油酸变位酶刚性对接LibDock 140分以上的化合物

图2 化合物与2，3-二磷酸甘油酸变位酶的分子对接模式图

表2 各组红细胞中2，3-二磷酸甘油酸含量

表3 不同缺氧时间对红细胞谷胱甘肽含量、过氧化氢酶活性和丙二醛含量的影响

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