前列欣胶囊对角叉菜胶致慢性非细菌性前列腺炎的代谢组学研究  

Qianliexin Capsules for carrageenin-induced chronic nonbacterial prostatitis:A metabolomics study

作　　者：宁玻[1] 臧凌鹤[2] 张亚 董文尧 NING Bo;ZANG Ling-he;ZHANG Ya;DONG Wen-yao(Department of Andrology,Linyi Peoples Hospital,Linyi,Shandong 273034,China;Shenyang Pharmaceutical University,Shenyang,Liaoning 110016,China;Research Institute of Chinese Materia Medica,Shandong Hongjitang Pharmaceutical Group Co.,Ltd.,Jinan,Shandong 250103,China;First School of Clinical Medicine,Shandong University of Chinese Medicine,Jinan,Shandong 250355,China)

机构地区：[1]临沂市人民医院男科,山东临沂273034 [2]沈阳药科大学,辽宁沈阳110016 [3]山东宏济堂制药集团股份有限公司中药研究院,山东济南250103 [4]山东中医药大学第一临床医学院,山东济南250355

出　　处：《中华男科学杂志》2023年第2期165-173,共9页National Journal of Andrology

基　　金：“十三五”国家重点研发计划(2017YFC1702704);泉城市“5150”人才倍增计划创新人才项目(2017017)。

摘　　要：目的:探索中药复方前列欣胶囊治疗慢性非细菌性前列腺炎的调控机制。方法:选取SPF级SD雄性大鼠18只,随机分为对照组、模型组、前列欣胶囊给药组,每组6只,各组均手术暴露前列腺侧叶,模型组与给药组于两侧叶注射50μl 1%角叉菜胶建立慢性非细菌性前列腺炎大鼠模型,对照组注射等量生理盐水。模型建立成功后,前列欣组按4 g/kg剂量灌胃给药,每日3次,对照组给予同等剂量纯净水。给药45 d后测定慢性非细菌性前列腺炎可能产生的下尿路症状,包括前列腺指数、组织炎症因子IL-1β、24 h排尿量、痛阈反应时间,并对尿液和血浆样品进行代谢组学分析。结果:与对照组相比,模型组前列腺系数显著增加[(0.75±0.09)‰vs(1.60±0.35)‰,P<0.01],前列腺组织中炎症因子IL-1β水平显著升高[(55.12±4.94) ng/ml vs(22.61±2.77) ng/ml,P<0.01];与模型组相比,前列欣胶囊给药组大鼠前列腺系数及IL-1β水平均显著降低[分别为(0.97±0.10)‰,(36.64±7.25) ng/ml,P<0.01]。下尿路症状考察结果显示:模型组表现出尿量显著减少,从对照组的16.38 ml降至4 ml(P<0.01),疼痛反应时间显著减少[(13.83±5.67) s vs(23.73±2.52) s,P<0.01],尿素氮、肌酐、尿酸肾功能相关指标显著增加[分别为(23.06±3.71) mg/dl vs(17.92±1.41) mg/dl,(48.08±9.31)μmol/L vs(40.31±3.53)μmol/L,(181.36±64.06)μmol/L vs(84.33±21.40)μmol/L,P<0.01],前列欣处理后显著改善上述症状[尿量(13.44±2.26) ml,疼痛时间(31.45±2.96) s,尿素氮(16.49±1.86)mg/dl,肌酐(36.88±7.98)μmol/L,尿酸(117.47±40.09)μmol/L,vs模型组,P<0.01]。代谢组学分析结果显示:角叉菜胶所致慢性非细菌性前列腺炎在尿液与血清中均有多种代谢物显示出显著差异,而前列欣治疗显示逆转作用。在尿液样本中,与前列欣作用密切相关的生物标志物包括天冬氨酸顺-S-氧化物等21个代谢物,表现为诸如甘氨醛、半胱氨酸、酮亚胺等在模型组中显�Objective:To explore the regulating mechanism of the Chinese medicinal compound Qianliexin Capsules(QLX)in the treatment of chronic nonbacterial prostatitis(CNP).MAethods:We randomly divided 18 SPF SD male rats into a normal control(n=6),a model control(n=6)and a QLX group(n=6).After successful establishment of a CNP model in the latter two groups by injecting 50μl 1%carrageenan bilaterally into the prostate,we treated the rats in the QLX group by intragastrical administration of QLX at 4 g/kg,tid,and those in the normal and model control groups with the same volume of pure water,all for 45 days.Then,we examined the possible lower urinary tract symptoms(LUTS)of CNP by detecting the prostate indexes,expression of the tissue inflammatory factor IL-1β,24-hour urine volume and pain threshold reaction(PTR)time,and conducted a metabonomics analysis of the urine and plasma samples.Results:Compared with the normal controls,the CNP model rats showed dramatically increased prostate coefficient([0.75±0.09]%o us[1.60±0.35]%o,P<0.01)and the expression of IL-1β([22.61±2.77]us[55.12±4.94]ng/ml,P<0.01),which were both decreased in the QLX group([0.97±0.10]%o and[36.64±7.25]ng/ml in comparison with those in the model controls(P<O.01).The urine volume was remarkably reduced in the model control group compared with that in the normal controls(4 ml us 16.38 ml,P<0.01),and so was the PTR time([13.83±5.67]vs[23.73±2.52]s,P<0.01),while the levels of urea nitrogen([23.06±3.71]us[17.92±1.41]mg/dL,P<0.01),creatinine([48.08±9.31]us[40.31±3.53]μmol/L,P<0.01)and uric acid([181.36±64.06]vs[84.33±21.40]μmol/L,P<0.01)increased significantly.The animals in the QLX group exhibited significant improvement in the urine volume([13.44±2.26]ml),PTR time([31.45±2.96]s),urea nitrogen([16.49±1.86]mg/dL),creatinine([36.88±7.98]μmol/L)and uric acid([117.47±40.09]μmol/L)in comparison with the model controls(P<0.01).Metabonomics analysis revealed a reversing effect of QLX on the carrageenin-induced alteration in a variety of metabol

关 键 词：前列欣胶囊 慢性非细菌性前列腺炎 代谢组学 角叉菜胶 大鼠 

分 类 号：R697.33[医药卫生—泌尿科学] R277.5[医药卫生—外科学]