曹惠敏 刘冬书 雷宁 李延晖 张蓉

〔摘要〕 目的 基于代謝组学初步探究补肾解毒方对辐射损伤大鼠的防护作用机制。方法 将60只雄性Wistar大鼠随机分为假照射组、2 Gy辐射模型组、4 Gy辐射模型组、2 Gy补肾解毒方干预组和4 Gy补肾解毒方干预组，每组12只，假照射组和辐射模型组给予生理盐水灌胃，补肾解毒方干预组给予补肾解毒方灌胃[组方生药等效剂量9.45 g/（kg·d）]，连续灌胃10 d。第11 天，除假照射组外，其余组均进行相应剂量的γ射线全身辐射，辐射后24 h和72 h分别收集各组大鼠血清，高效液相色谱串联质谱靶向检测大鼠血清中氨基酸和酰基肉碱的含量。结果 与假照射组相比，辐射大鼠血清代谢轮廓明显改变，血清中赖氨酸含量明显升高（P<0.01），瓜氨酸、谷氨酸、组氨酸、脯氨酸含量明显降低（P<0.01），十四碳烯酰肉碱和苏氨酸水平先降低后升高（P<0.01）。与辐射模型组相比，补肾解毒方可改善辐射大鼠血清代谢轮廓，明显回调辐射大鼠血清中瓜氨酸、谷氨酸、组氨酸、赖氨酸、脯氨酸、苏氨酸、十四碳烯酰肉碱含量（P<0.01或P<0.05），改善精氨酸生物合成、精氨酸和脯氨酸代谢、组氨酸代谢、D-谷氨酰胺和D-谷氨酸代谢等途径。结论 补肾解毒方可能通过回调辐射大鼠血清中部分氨基酸和酰基肉碱含量，改善相关代谢通路，发挥辐射防护作用。

〔关键词〕 补肾解毒方;辐射;代谢组学;氨基酸;酰基肉碱

〔中图分类号〕R285.5       〔文献标志码〕A       〔文章编号〕doi：10.3969/j.issn.1674-070X.2021.06.007

Mechanism of Radiation Injury Protection of Rats of Bushen Jiedu Prescription

Based on Metabonomics

CAO Huimin1，2， LIU Dongshu2，3， LEI Ning2， LI Yanhui2， ZHANG Rong2*

（1. School of Pharmacy， Soochow University， Suzhou， Jiangsu 215021， China; 2. Rocket Army Characteristic Medical Center， Beijing 100088， China; 3. Jinzhou Medical University， Jinzhou， Liaoning 121001， China）

〔Abstract〕 Objective To explore the protective mechanism of Bushen Jiedu Prescription on radiation-damaged rats based on metabonomics. Methods 60 male Wistar rats were randomly divided into sham radiation group， 2 Gy radiation model group， 4 Gy radiation model group， 2 Gy Bushen Jiedu Prescription intervention group and 4 Gy Bushen Jiedu Prescription intervention group， with 12 rats in each group. Sham radiation group and radiation model groups were given normal saline by gavage， and the Bushen Jiedu Prescription intervention groups were given Bushen Jiedu Prescription [equivalent dose of crude drug was 9.45 g/（kg·d）] by gavage， for 10 consecutive days. On the 11th day， except for the sham irradiation group， the other groups received corresponding doses of γ-ray whole body radiation. After 24 hours and 72 hours after irradiation， the serum of rats of each group was collected. The content of amino acids and acylcarnitine in the blood of rats was detected by high performance liquid chromatography-mass spectrometry. Results Compared with the sham irradiation group， the serum metabolic profile of irradiated rats changed significantly （P<0.01）. The content of lysine in the serum was significantly increased （P<0.01）， the content of citrulline， glutamic acid， histidine， proline was significantly reduced （P<0.01）， and the levels of tetradecenoyl carnitine and threonine first decreased and then increased （P<0.01）. Compared with the radiation model group， Bushen Jiedu Prescription improved the serum metabolic profile of irradiated rats. The content of citrulline， glutamic acid， histidine， lysine， proline， threonine， and tetradecenoyl carnitine in the serum of irradiated rats was significantly returned （P<0.01 or P<0.05）， and improved arginine biosynthesis， arginine and proline

metabolism， histidine metabolism， D-glutamine and D-glutamate metabolism and other metabolic pathways. Conclusion Bushen Jiedu Prescription may improve the related metabolic pathways and exert radiation protection by adjusting the content of some amino acids and acylcarnitine in the serum of irradiated rats.

〔Keywords〕 Bushen Jiedu Prescription; radiation; metabolomics; amino acids; acylcarnitine

近年來，辐射在便利人们生活的同时，也带来了意想不到的伤害，切尔诺贝利、福岛、达喀尔等核事故加重了人类对辐射的担忧[1-2]。辐射引起基因、mRNA、蛋白质等代谢过程紊乱，损伤机体多个层面，造成体内代谢物的异常消耗或蓄积[3]。代谢组学是检测环境改变后，生物体内源性小分子物质变化及变化规律的一门学科，通过高通量检测手段对生物体小分子物质进行定性和定量检测，动态监测并反映生物表型变化[4-5]。

中医药是我国瑰宝，具有低毒高效、防治结合的特点，已广泛用于辐射损伤的研究[6]。张蓉等[7-9]通过对辐射病症进行分析，从五脏角度提出了从肾……