摘要
本研究运用药理学结合代谢组学技术探究蒙古扁桃药材总提物对博来霉素致大鼠肺纤维化的影响。通过气管内注射博来霉素建立肺纤维化大鼠模型后给予蒙古扁桃治疗,苏木精-伊红(hematoxylin and eosin,HE)、Masson染色评估肺组织病理变化,检测血清和肺组织中超氧化物歧化酶(superoxidedismutase,SOD)活性和丙二醛(malondialdehyde,MDA)含量,荧光定量PCR检测肺组织中转化生成因子β1(transforming growth factorβ1,TGF-β1)、Smad家族蛋白3(Smad family member 3,Smad3)和α平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)通路指标表达,UPLC-Q-TOF/MS进行血清代谢组学研究,探究生物标志物的变化规律和影响的代谢通路。结果表明,与模型组比较,(1.5 g·kg^(-1))、高(3.0 g·kg^(-1))剂量蒙古扁桃总提物可显著降低肺纤维化大鼠肺指数,显著升高血清和肺组织SOD活性,减轻大鼠肺泡炎症和肺纤维化程度,降低血清和肺组织中MDA,并显著降低肺组织中TGF-β1、Smad3和α-SMA mRNA的表达。血清代谢组学轮廓分析鉴定出25个显著差异代谢物,其中蒙古扁桃总提物可以通过降低LysoPE(0∶0/22∶5(4Z,7Z,10Z,13Z,16Z))、LysoPC(20∶0/0∶0)、PC(20∶5(5Z,8Z,11Z,14Z,17Z)/15∶0)、12,13-二羟基-9-十八烯酸(12,13-DHOME)、9,10-二羟基-12-十八烯酸(9,10-DHOME)5个关键生物标志物参与亚油酸代谢、甘油磷脂代谢、亚麻酸代谢途径影响肺纤维化。该研究初步揭示了蒙古扁桃总提物抗大鼠肺纤维化的作用机制,为蒙古扁桃的临床应用提供参考依据。动物实验经内蒙古科技大学包头医学院医学伦理委员会批准(批准号:20170315)。
This study used pharmacology combined with metabolomics to explore the effect of Amygdalus mongolica total extract on bleomycin induced pulmonary fibrosis in rats.The rat model of pulmonary fibrosis was established by intratracheal injection of bleomycin and treated with the total extract of Amygdalus mongolica.The pathological changes of lung tissue were evaluated by hematoxylin and eosin(HE)and Masson staining,the contents of superoxide dismutase(SOD)and malondialdehyde(MDA)in lung tissue were detected,and transforming growth factorβ1(TGF-β1),Smad family member 3(Smad3),α-smooth muscle actin(α-SMA)pathway index expression in lung tissue was detected by fluorescence quantitative PCR.UPLC-Q-TOF/MS was used to study serum metabolomics to explore the changing patterns of biomarkers and the metabolic pathways affected by them.The results showed that compared with the model group,the medium(1.5 g·kg^(-1))and high(3.0 g·kg^(-1))doses of Amygdalus mongolica total extract could significantly reduce the lung index,significantly increase the activity of SOD in serum and lung tissue,reduce the degree of alveolar inflammation and pulmonary fibrosis,and reduce MDA in serum and lung tissue,and significantly reduce TGF-β1,Smad3,α-SMA mRNA expression in lung tissue.Serum metabolomics profile analysis identified 25 significantly different metabolites,the Amygdalus mongolica total extract can participate in linoleic acid metabolism,glycerophospholipid metabolism and alpha-linolenic acid metabolism by reducing five key biomarkers:lysoPE(0∶0/22∶5(4Z,7Z,10Z,13Z,16Z)),lysoPC(20∶0/0∶0),PC(20∶5(5Z,8Z,11Z,14Z,17Z)/15∶0),12,13-dihydroxy-9-octadecenoic acid(12,13-DHOME),9,10-dihydroxy-12-octadecenoic acid(9,10-DHOME)to affect pulmonary fibrosis.This study preliminarily revealed the action mechanism of Amygdalus mongolica total extract against pulmonary fibrosis in rats,and provided a reference basis for the clinical application of Amygdalus mongolica.The animal experiments were approved by the Medical Ethics Committee of Baotou Medical College(No.20170315).
作者
刘佳琦
周红兵
权博文
白万富
王佳
白迎春
常虹
石松利
LIU Jia-qi;ZHOU Hong-bing;QUAN Bo-wen;BAI Wan-fu;WANG Jia;BAI Ying-chun;CHANG Hong;SHI Song-li(Department of Pharmacy,Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014060,China;Institute of Bioactive Substance and Function of Mongolian Medicine and Chinese Materia Medica,Baotou Medical College of Inner Mongolia University of Science and Technology,Baotou 014060,China)
出处
《药学学报》
CAS
CSCD
北大核心
2022年第8期2484-2493,共10页
Acta Pharmaceutica Sinica
基金
国家自然科学基金项目(81641137,81760782,82060784)
内蒙古自治区“草原英才工程”青年创新创业人才项目(一层次人选,No.Q2017046)
内蒙古自治区第十一批“草原英才”工程人才项目[(2021)8]
内蒙古自然科学基金项目(2019MS08189)
内蒙古自治区高等学校科学研究项目[NJZY21048].
关键词
蒙古扁桃
肺纤维化
代谢组学
药理学
作用机制
Amygdalus mongolica
pulmonary fibrosis
metabolome
pharmacology
mechanism of action
