Imikhiqizo

Isifo sesibindi esinamafutha angenaso utshwala (i-NAFLD) sinezinhlobo eziningi zezifo ezisukela ku-steatosis encane ebonakala ngokugcinwa okungavamile kwama-lipids ngaphakathi kwamaseli esibindi kuya ku-steatohepatitis (NASH) okubonisa ukunqwabelana kwamafutha, ukuvuvukala, ibhaluni kanye nokuwohloka kwe-hepatocytes, kanye ne-fibrosis.Ekugcineni, i-steatohepatitis ingaholela ekuqineni kwesibindi kanye ne-hepatocellular carcinoma.Kulolu cwaningo sihlaziye izinhlobo ezintathu zamagundane ezihlukene, i-A/J, i-C57BL/6J, ne-PWD/PhJ, ekhombisa amazinga ahlukene e-steatohepatitis lapho kulawulwa i-3,5-diethoxycarbonyl. -1,4-dihydrocollidine (DDC) equkethe ukudla.Ukuhlaziywa kokuchazwa kofuzo lwe-RNA-Seq, ukuhlaziya amaprotheni kanye nokuchazwa kwe-metabolic kwasetshenziswa ukuze kuhlonzwe izakhi zofuzo/amaprotheni avezwe ngokwehlukana kanye namazinga e-metabolite aphazamisekile amasampula esibindi segundane ekwelashweni kwe-DDC.Ukuhlaziywa kwendlela yembula ukushintshwa kwe-arachidonic acid (AA) ne-S-adenosylmethionine (SAMe) metabolism kwezinye izindlela.Ukuze uqonde izinguquko ze-metabolic ye-arachidonic aci d metabolism ekukhanyeni kwamaphrofayli enkulumo yesifo imodeli ye-kinetic yale ndlela yasungulwa futhi yenziwa kahle ngokuya ngamazinga we-metabolite.Ngokulandelayo, imodeli yasetshenziselwa ukutadisha emiphumeleni ye-silico yezinhloso zezidakamizwa ezingase zibe khona ze-steatohepatitis.Sihlonze i-AA/eicosanoid metabolism njengephazamisekile kakhulu kumagundane enziwe yi-DDC kusetshenziswa inhlanganisela yokuhlola kanye nendlela ye-silico.Ukuhlaziywa kwethu kwendlela ye-AA/eicosanoid ye-metabolic kuphakamisa ukuthi i-5-hydroxyeicosatetraenoic acid (5-HETE), i-15-hydroxyeicosatetraenoic acid (15-HETE) kanye ne-prostaglandin D2 (PGD2) iphazamisekile kumagundane e-DDC.Siphinde sibonisa ukuthi imodeli eguquguqukayo ingasetshenziselwa ukubikezela ikhwalithi yezinguquko ze-metabolic ngokusekelwe kudatha ye-transcriptomics kumongo ohlobene nesifo.Ngaphezu kwalokho, i-SAMe metabolism yabonakala iphazamisekile ngenxa yokwelashwa kwe-DDC.Izakhi zofuzo ezimbalwa kanye namanye ama-metabolite ale mojula abonisa umehluko phakathi kwe-A/J ne-C57BL/6J ngakolunye uhlangothi ne-PWD/PhJ ngakolunye.