雨生红球藻抑制肺成纤维细胞向肌成纤维细胞转化改善博来霉素诱导的小鼠肺纤维化

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Haematococcus pluvialis alleviates bleomycin-induced pulmonary fibrosis in mice by inhibiting transformation of lung fibroblasts into myofibroblast
ZHANG Xiao,MANJingzhou1,ZHANGYong2,ZHENGYunJian2,WANGHeping1,YUANYijun1,XIEXi ²
Abstract:ObjectiveToinvestigatetheefectofHaematococcuspluuialis(HP)onbleomcin(BLM-inducedpulmonaryfbrosis inmiceandonTGF-β1-inducedhuman fetal lungfibroblasts (HFL1).Methods ThirtymaleC57BL/6micewererandomly dividedintootrolgroup,ducedmoarybrosisodelgrouplodgdoseHreamentgou(d21 mg/kg, respectively),and 300mg/kg pirfenidone (positivecontrol) group. Theeffectsof drug treatment for 21 dayswere assessedbyangspatoryfutiolngtoptholgnexpsiofrosskesinteungtsofte mouse models. In TGF-β1-induced HFL1 cell cultures,the effects of treatment with120,180 and 240μg/mL HP or pirfenidone for 48h on expression levels of fibrosis markers were evaluated. Transcriptome analysis was carried out using the control cells and cells treated with TGF-β1 and 240μg/mL HP. Results HP obviously alleviated BLM-induced lung function damageandfibroticchanges inmice,evidencedbyimprovedrespiratoryfunction,lungtisue morphologyandstructure inflammatoryifilration,ndcollagendepositioandducedexresionsoffroticproteis.Hatteighosepouced similar effect to PFD. In TGF-β1-induced HFL1 cells, treatmentwith 240μg/mL HP significantly reduced the mRNA and protein expression levels of α -SMAand FN. Transcriptome analysisrevealed that multiple key genesand pathways mediated theprotectiveefectofHPagainstpulmonaryfibrosis.ConclusionHPaleviatespulmonaryfibrosisinboththemousemodel andcellmodel,possiblyastheresult of thesynergisticeffectsof itsmultipleactivecomponents.
Keywords:Haematococcuspluuialis;pulmonary fibrosis;bleomycin;fibroblast
肺纤维化是一种进展性的纤维化肺部疾病,主要表现为成纤维细胞异常增殖分化、细胞外基质过度沉积以及间充质转化,导致健康肺组织气体交换功能受损,进而引起呼吸衰竭和死亡,该进程具有不可逆性[2]。(剩余16638字)