| Rahi: | |
|---|---|
E tika ana mo te haumanu – Ka whakahoki ano i te SSc-ILD tangata me te fibrosis pulmonary, fibrosis kiri, me te pathology takawaenga TGF-β.
Nga pito matawhānui – Te taumaha o te tinana, te teitei o te toia kiri (te kiri fibrosis), te mahi pūkahukahu, te rere o te cytometry (te kuhutanga o te pūtau ārai mate), te histopathology pūkahukahu (HE & Masson staining).
Ko te mahi a te miihini - Ko te BLM te whakararu i te kino o te DNA, te ahotea oxidative, me te whakahohe ara TGF-β, te whakaata i te pathogenesis SSc-ILD tangata.
Te uara whakawhiti - He pai mo te whakamatautau i nga kaihoko anti-fibrotic (nintedanib, pirfenidone), TGF-β inhibitors, me te immunomodulators.
Nga kohinga raraunga kua rite IND - Ka taea te whakahaere rangahau i runga i nga tikanga o te GLP.
BLM Induced C57BL/6 SSc-ILD Tauira
• Te whakamatautau whai hua o nga kaitautoko anti-fibrotic (nintedanib, pirfenidone, TGF-β inhibitors, galectin-3 inhibitors)
• Te arotakenga o nga immunomodulators e aro ana ki te mumura me te fibrosis
• Te whakamanatanga whainga mo te tohu tohu TGF-β me nga huarahi fibrotic
• Te kitenga o te tohu koiora (nga tohu collagen, nga takawaenga mumura, nga waitohu pūtau aukati)
• Maatauranga rongoora me te paitini whakaahei IND
Tawhā |
Whakatakotoranga |
Momo/Riki |
C57BL/6 kiore |
Tikanga whakauru |
Intratracheal instillation o bleomycin (BLM, 1–2 U/kg) i roto i te tote, horopeta kotahi |
Te roanga ako |
14–28 ra (whakawhanaketanga fibrosis) |
Nga pito mutunga matua |
Te taumaha o te tinana, te teitei o te kumete kiri (te kiri fibrosis), te mahi o te pukahukahu (te tutukitanga, te aukati), te rere cytometry (te urunga o te pūtau mate: macrophages, neutrophils, T cell), te hiipapa o te pūkahukahu (HE me te Masson trichrome whakakikorua ki te kaute Ashcroft), ka taea: te ihirangi hydroxyproline, nga tatau pūtau BALF, nga taumata cytokine |
| Te whakahaere pai | Ko te Nintedanib me te pirfenidone e waatea ana hei tohutoro pūhui anti-fibrotic |
Mōkihi Raraunga |
Raraunga mata, pūrongo tātaritanga, raraunga mahi pūkahukahu, rerenga rerenga cytometry, kiriata histology (HE, Masson), bioinformatics (kōwhiringa) |
A1: Ka whakaratohia e matou he tauira SSc-ILD bleomycin (BLM)-induced ma te whakamahi i nga kiore C57BL/6 mo te rangahau mate e pa ana me te aromatawai tarukino.
A2: Ma te BLM ka pakaru te DNA me te ahotea waiora i roto i te kiko pukahukahu. Ka whakahoahohia te mumura mau tonu me te whakatikatika o te kiko kino, ka peia te fibrosis pūkahukahu ma te ara TGF-β, e whakahoki ana i nga ahuatanga pathological o te tangata SSc-ILD.
A3: Ka aroturuki matou i te taumaha o te tinana me te whakamatautau i te mahi o te huhu. Ka kitea ano e matou nga cytokine mumura, ka mahia he tātaritanga cytometry rere, ka whakahaere hoki i te whakamaarama HE me te Masson mo te aromatawai pathological pūkahukahu.
A4: Ka whakahaerehia te BLM i te Ra 0. Ka whakahaerehia nga whakamatautau mo te mahi paru i te Ra 34, ka mutu te whakamatautau katoa i te Ra 35.
