基于非靶向尿液代谢组学探究前列金丹片对慢性非细菌性前列腺炎大鼠的作用机制  

Action mechanisms of Qianlie Jindan Tablets on chronic nonbcterial prostatitis in rats:An exploration based on non-targeted urine metabolomics

作　　者：陈腾飞 贾志超 史卓卓 马俊国 李啸林 仲崇副[1] CHEN Teng-fei;JIA Zhi-chao;SHI Zhuo-zhuo;MA Jun-guo;LI Xiao-lin;ZHONG Chong-fu(Department of Urology and Andrology,The Affiliated Hospital of Shandong University of Chinese Medicine,Jinan,Shandong 250014,China;Shandong University of Chinese Medicine,Jinan,Shandong 250014,China;Shandong Zhongda Pharmaceutical Co.,Ltd,Jinan,Shandong 250204,China)

机构地区：[1]山东中医药大学附属医院泌尿男科,山东济南250014 [2]山东中医药大学,山东济南250014 [3]山东中大药业有限公司,山东济南250204

出　　处：《中华男科学杂志》2024年第6期531-539,共9页National Journal of Andrology

基　　金：山东中医药大学附属医院横向课题(H20220424-01)。

摘　　要：目的:基于非靶向尿液代谢组学探究前列金丹片对慢性非细菌性前列腺炎大鼠的作用机制。方法:将30只8周龄雄性SD大鼠按照体质量随机分为空白组、模型组和药物组,每组10只。模型组和药物组制备慢性非细菌性前列腺炎大鼠模型(大鼠前列腺两侧叶均注入0.2 ml弗氏完全佐剂)。从造模的第4天开始,空白组和模型组予生理盐水灌胃,药物组予前列金丹片混悬液灌胃,每日1次,连续灌胃30 d。实验结束后用超高效液相色谱-串联静电场轨道阱质谱联用仪检测各组大鼠的代谢物变化,并通过多元统计分析等鉴定各组间的差异代谢物,然后对差异代谢物进行功能注释。结果:代谢组学分析得到8个共同代谢物,其中5个代谢物在模型组表达下降,在药物组表达升高(P<0.05);其他3个代谢物在模型组表达升高,在药物组表达下降(P<0.05)。其中肌酐和染料木黄酮是重要差异代谢物,精氨酸和脯氨酸代谢通路以及异黄酮生物合成通路是前列金丹片发挥治疗作用的主要通路。与空白组相比,模型组精氨酸和脯氨酸代谢通路上调,肌酐生成增多(P<0.05);异黄酮生物合成通路下调,染料木黄酮生成减少(P<0.05)。与模型组相比,药物组逆转了上述变化。结论:前列金丹片通过调节精氨酸和脯氨酸代谢通路干预L-精氨酸代谢,以及调节异黄酮生物合成通路干预柚皮素代谢,发挥对慢性非细菌性前列腺炎大鼠的治疗作用。Objective:To explore the mechanisms of Qianlie Jindan Tablets(QLJD)acting on chronic nonbacterial prostatitis(CNP)in rats based on non-targeted urine metabolomics.Methods:According to the body mass index,we equally randomized 30 eight-week-old male SD rats into a blank control,a CNP model control and a QLJD medication group.We established the CNP model in the latter groups and,from the 4th day of modeling,treated the rats in the blank and model control groups intragastrically with normal saline and those in the QLJD medication group with QLJD suspension,qd,for 30 successive days.Then we detected the changes in the metabolites of the rats by ultra-high-performance liquid chromatography-tandem mass spectrometry,and identified the differential metabolites in different groups by multivariate statistical analysis,followed by functional annotation of the differential metabolites.Results:Eight common metabolites were identified by metabolomics analysis,of which 5 were decreased in the CNP model controls and increased in the QLJD medication group,while the other 3 increased in the former and decreased in the latter group.Creatinine and genistein were important differential metabolites,and the arginine and proline metabolic pathways and isoflavone biosynthesis pathways were the main ones for QLJD acting on CNP.Compared with the blank controls,the model controls showed up-regulated arginine and proline metabolic pathways,increased production of creatinine,down-regulated isoflavone biosynthetic pathway and decreased production of genistein.The above changes in the model controls were all reversed in the QLJD medication group.Conclusion:QLJD acts effectively on CNP in male rats by regulating L-arginine and proline metabolic pathways,as well as the isoflavone biosynthesis pathway and naringenin metabolism.

关 键 词：慢性非细菌性前列腺炎 超高效液相色谱-质谱 尿液代谢组学 精氨酸 柚皮素 染料木黄酮 

分 类 号：R697.33[医药卫生—泌尿科学]