复方石榴子胶囊对大鼠溃疡性结肠炎的治疗作用及代谢组学的初步研究  

Pharmacological Effects and Metabonomics of Shiliuzi(石榴子) Compound Capsules on Ulcerative Colitis

作　　者：霍仕霞 康雨彤 张数数 祖力皮卡尔·吾斯曼 斯拉甫·艾白 李治建 邢建国[1,4] HUO Shixia;KANG Yutong;ZHANG Shushu;Zulipikaer-Wusiman;Silafu-Aibai;Li Zhijian;XING Jianguo(College of Medicine,Xinjiang Medical University,Urumqi 830011;Hospital of Xinjiang Uighur Medicine,Urumqi 830049;Xinjiang Institute of Traditional Uighur Medicine,Urumqi 830049;Xinjiang Institute of Materia Medica,Urumqi 830002)

机构地区：[1]新疆医科大学药学院,乌鲁木齐830011 [2]新疆维吾尔自治区维吾尔医医院,乌鲁木齐830049 [3]新疆维吾尔自治区维吾尔医药研究所,乌鲁木齐830049 [4]新疆维吾尔自治区药物研究所,乌鲁木齐830002

出　　处：《中药药理与临床》2023年第6期36-43,共8页Pharmacology and Clinics of Chinese Materia Medica

基　　金：新疆维吾尔自治区重大科技专项基金(编号:2016A03005);天山英才项目(编号:2022TSYCCX0021,2022TSYCLJ009);中医药传承与创新“百千万”人才工程(岐黄工程)-青年岐黄学者。

摘　　要：目的:研究复方石榴子胶囊对大鼠溃疡性结肠炎(Ulcerative colitis,UC)药效作用及其结肠内源性代谢物的影响。方法:SD大鼠随机分为正常对照组、模型对照组、复方石榴子胶囊4.32 g生药/kg组和美沙拉嗪0.4 g/kg组,除正常对照组外,其余各组采用2,4,6-三硝基苯磺酸(2,4,6-Trinitrobenzene sulfonic acid,TNBS)诱导UC模型,24 h后给予相应药物灌胃给药7 d,采用疾病活动指数(DAI)及结肠病理评价其疗效;ELISA法测定血清中IgG、IgA、TNF-α、IL-1的含量;采用LC-MS技术,测定结肠组织内源性代谢物水平,通过主成分分析(PCA)和正交偏最小二乘法-判别分析(OPLS-DA)筛选出潜在差异代谢物及可能的代谢通路。结果:经复方石榴子胶囊4.32 g生药/kg干预后,与模型对照组比较,UC大鼠的DAI明显降低(P<0.05),结肠病理状态明显好转;血清中IgA、IgG、TNF-α、IL-1含量显著降低(P<0.01);差异代谢物苯丙氨酰甘氨酸、L-丝氨酸、D-葡萄糖醛酸、等多种代谢物的水平发生变化,同时对嘧啶代谢、氰基氨基酸代谢等11条代谢通路产生影响。结论:复方石榴子胶囊治疗UC的作用机制,可能与免疫调控、氨基酸代谢和能量代谢有关。Objective:To investigate the pharmacological effects of Shiliuzi(石榴子) Compound Capsules on ulcerative colitis(UC) in rats and its influence on endogenous metabolites in the colon.Methods:SD rats were randomly divided into a normal control group,a model control group,a Shiliuzi Compound Capsules group(4.32 g/kg),and a mesalazine group(0.4 g/kg).The UC model was induced in rats except for those in the normal control group by 2,4,6-trinitrobenzene sulfonic acid.After 24 hours,the corresponding drugs were administered orally for 7 days.The therapeutic efficacy was evaluated using the disease activity index(DAI) and colon histopathology.The levels of IgG,IgA,TNF-α,and IL-1 in serum were measured by ELISA.LC-MS technology was used to measure the levels of endogenous metabolites in colon tissues.Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were used to identify potential differential metabolites and possible metabolic pathways.Results:Compared with the model control group,the Shiliuzi Compound Capsules group showed decreased DAI of UC rats(P<0.05),improved colon pathological conditions,reduced levels of IgA,IgG,TNF-α,and IL-1 in serum(P<0.01),and altered levels of differential metabolites,such as phenylalanyl glycine,L-serine,and D-glucuronate.Eleven metabolic pathways,including pyrimidine metabolism and cyano-amino acid metabolism,were affected.Conclusion:The mechanism of action of Shiliuzi Compound Capsules in treating UC may be related to immunoregulation,amino acid metabolism,and energy metabolism.

关 键 词：复方石榴子胶囊 溃疡性结肠炎 代谢组学 代谢通路 

分 类 号：R285.5[医药卫生—中药学]