基于粪便代谢组学技术丹贝益肺方对肺纤维化伴抑郁大鼠的作用机制研究  

Effect of Danbei Yifei formula on fecal metabolomics in rats with pulmonary fibrosis and depression

作　　者：蔡萧君 王钦 江柏华 刘松 李宇 吴圆圆 胡杨 颉彦鹏 CAI Xiaojun;WANG Qin;JIANG Baihua;LIU Song;LI Yu;WU Yuanyuan;HU Yang;XIE Yanpeng(Department of Endocrinology,Heilongjiang College of Traditional Chinese Medicine,Harbin 150036,China)

机构地区：[1]黑龙江省中医药科学院内分泌科,哈尔滨150036

出　　处：《山西医科大学学报》2022年第2期175-181,共7页Journal of Shanxi Medical University

基　　金：黑龙江省应用技术研究与开发计划项目(GA19C108);黑龙江省自然科学基金面上项目(H2017043)。

摘　　要：目的基于超高液相-静电场轨道阱技术(UHPLC-Q-Orbitrap)的代谢组学技术研究丹贝益肺方对肺纤维化伴抑郁症大鼠粪便中内源性生物标记物的影响,阐明肺纤维化伴抑郁症大鼠的发病机制及丹贝益肺方的药物作用机制。方法24只雄性SD大鼠按体质量随机分为3组:对照组、模型组和丹贝益肺方组。模型组和丹贝益肺方组均采用气管注射博莱霉素(5 mg/kg)同时联合腹腔注射脂多糖(1 mg/kg)方法诱导肺纤维化伴抑郁症大鼠模型,丹贝益肺方组另外给与丹贝益肺方水煎液(0.6 g/100 g)进行治疗。测定两组大鼠的生化指标,包括超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)。在此基础上对大鼠粪便进行非靶向代谢组学分析,发现生物标记物,阐明发病机制。结果与对照组相比,模型组大鼠大脑前额皮质的IL-1β、IL-6和TNF-α显著升高(P<0.05),血清中SOD、GSH和MDA显著降低(P<0.05)。大鼠定位航行能力结果显示,与模型组比较,丹贝益肺方组定位平台时间明显减少(P<0.01)。粪便代谢组学研究结果显示,模型组与对照组的代谢轮廓明显分开。与对照组相比,模型组大鼠的代谢异常与5个代谢产物相关,分别为3-羟基癸酰肉碱(3-hydroxydecanoyl carnitine)、溶血磷脂酰胆碱(LysoPC(10∶0/0∶0))、肌苷(inosine)、硫酸雄甾酮(androsterone sulfate)、犬尿酸(L-kynurenine),主要涉及嘌呤代谢、色氨酸代谢异常等。与模型组比,丹贝益肺方组5个生物标记物有降低趋势,但差异没有统计学意义;主成分分析图显示丹贝益肺方组整体代谢轮廓向对照组方向发展。结论丹贝益肺方对肺纤维化伴抑郁症有良好的疗效,调节嘌呤代谢、色氨酸代谢通路可能是其治疗肺纤维化伴抑郁症的作用机制。Objective To study the effect of Danbei Yifei formula on endogenous biomarkers in feces of rats with pulmonary fibrosis and depression based on UHPLC-Q-Orbitrap,and clarify the pathogenesis of rats with pulmonary fibrosis and depression and the action mechanism of Danbei Yifei formula.Methods Twenty-four male SD rats were randomly divided into three groups according to body weight:control group,model group and Danbei Yifei formula group.The rat model of pulmonary fibrosis with depression was induced by intratracheal injection of bleomycin(5 mg/kg)and intraperitoneal injection of lipopolysaccharide(1 mg/kg)in model group and Danbei Yifei formula group,and the rats were addiontionally treated with Danbei Yifei formula decoction(6 g/kg)in Danbei Yifei formula group.The biochemical indexes in the two groups were measured,including superoxide dismutase SOD,GSH,MDA and IL-1β,IL-6,TNF-α.On this basis,non-targeted metabolomics analysis of rat feces was carried out to find biomarkers and clarify the pathogenesis.Results Compared with control group,the contents of IL-1β,IL-6,TNF-αin the prefrontal cortex of rats in model group were significantly increased(P<0.05),while the contents of SOD,GSH and MDA in serum were decreased significantly(P<0.05).The results of positioning navigation ability of rats showed that compared with model group,the positioning platform time was significantly reduced in Danbei Yifei formula group(P<0.01).Fecal metabolomics study showed that the metabolic abnormalities of rats in model group were related to five metabolites:3-hydroxydecanoyl carnitine,LysoPC(10∶0/0∶0),inosine,androsterone sulfate,L-kynurenine,and they are involved in purine metabolism,abnormal tryptophan metabolism,etc.Compared with model group,the contents of biomarkers in Danbei Yifei formula group were decreased,and there was no significant difference.The principal component analysis showed that the overall metabolic profile in Danbei Yifei formula group developed towards control group.Conclusion Danbei Yifei formula has a

关 键 词：丹贝益肺方 肺纤维化 抑郁症 嘌呤代谢 色氨酸代谢 

分 类 号：R28[医药卫生—中药学]