| Rahi: | |
|---|---|
Te whai takenga haumanu — Ko te fibrosis a CCl4-induced e whakahoki ano i te fibrosis ate tangata me te whakahekenga o te matrix extracellular ahu whakamua me te mate ate.
Te pito mutunga - te taumaha o te tinana, te ALT me te AST serum (nga tohu whara ate), te taatai ate (HE, Masson trichrome, Sirius Red), te tohu fibrosis.
Ka taea te whakaputa me te tohu pai - he tauira e whakamahia nuitia ana me nga kawa kua pumau me te kaha o te whakaputa i roto i nga whakamatautau.
Te uara whakawhiti - he pai mo te whakamatautau i nga raau taero anti-fibrotic (nintedanib, pirfenidone), antioxidants me nga pūhui hepatoprotective.
IND Ready Packet – Ka taea te whakahaere rangahau i runga i nga tikanga o te GLP.
CCl4-induced C57BL/6 ate fibrosis tauira
• Te whakamatautau kaha o nga raau taero antifibrotic (nintedanib, pirfenidone, TGF-β inhibitors, galectin-3 inhibitors)
• Te arotake i nga raau taero hepatoprotective, antioxidants me nga pūhui anti-inflammatory
• Te whakamanatanga whainga o nga ara whiti (te whakahiato collagen, te whakahohenga pūtau stellate)
• Te kitenga o te tohu koiora (te tohu collagen, te ate enzymes, te takawaenga mumura)
• Nga rangahau rongoa me te paitini hei tautoko i te IND
whānuitanga |
Whakatakotoranga |
Momo/Riki |
C57BL/6 kiore |
tikanga whakauru |
Ko te werohanga o roto o te waro tetrachloride (CCl4, 0.5–1.0 mL/kg, rewa ki te hinu oriwa) e rua wiki mo te 4-8 wiki |
wā ako |
4–10 wiki (whakauru + wahanga maimoatanga) |
pito mutunga arohaehae |
Te taumaha o te tinana, nga taumata ALT me te AST serum (matū haumanu), histopathology ate (HE, Masson's trichrome, Sirius red fibrosis score), hei whiriwhiri: hydroxyproline content, serum albumin/bilirubin, immunohistochemistry (α-SMA, collagen I) |
| whakahaere pai | Ka taea te whakamahi i te Nintedanib me te pirfenidone hei tohutoro pūhui antifibrotic |
pākete |
Raraunga mata, purongo tātaritanga, matū haumanu, kiriata histology (HE, Masson, Sirius Red), bioinformatics (he kōwhiringa) |
Uiui: Me pehea te CCl4 e whakaawe ai i te fibrosis ate?
Whakautu: Ko te CCl4 ka whakakorikorihia e nga enzymes cytochrome P450 i roto i nga pūtau ate ki te whakaputa i nga rauropi koreutu trichloromethyl tino kaha, e puta ai te peroxidation lipid, te necrosis hepatocyte me te mumura. Ko te wharanga tukurua e arai ana ki te whakahohenga o te pūtau stellate, te nui o te tuunga matrix extracellular, me te fibrosis ate ahu whakamua.
P: He aha nga tino rite ki te fibrosis ate tangata?
A: Ko tenei tauira e whakaatu ana i te hekenga o te collagen deposition, elevated serum aminotransferases (ALT, AST), me nga huringa histopathological e tino rite ana ki te fibrosis ate tangata (bridging fibrosis, pseudolobule formation).
P: Ka taea te whakamahi i tenei tauira mo nga rangahau tautoko IND?
Whakautu: Ae. Ka taea te whakahaere rangahau i runga i nga tikanga GLP mo nga tukunga ture (FDA, EMA).
P: Ka tukuna e koe nga tikanga ako (hei tauira, rereke CCl4 pota, huarahi whakahaere, wa maimoatanga)?
Whakautu: Ko te akoranga. Ko ta matou roopu pūtaiao e whakarite ana i nga tikanga whakangaonga CCl4, nga raarangi whakangao, me nga tātaritanga mutunga i runga i to kaitono tarukino motuhake.
P: He aha te waarangi angamaheni mo te rangahau whaihuatanga pairati?
A: Ko nga rangahau pairati te nuinga o nga wiki 4-8 o te whakaurunga CCl4 me te maimoatanga i te wa kotahi, i muri ranei i te whakaturanga fibrosis.