动物造模,原发性硬化性胆管炎 z-bio 2022-01-04 701

　　Objective To explore the therapeutic effect of rapamycin on primary sclerosing cholangitis (PSC) in mice induced by 3,5-diethoxycarbonyl 1,4-dihydrocollidine (DDC), and explore its potential mechanism.

　　Methods Female C57BL/6J mice aged 6-8 weeks were randomly divided into a normal diet group, a DDC diet (0.1% DDC) model, and a DDC model + rapamycin (RAPA) treatment group. Paamycin (5 mg/kg body weight) was injected once a day for 7 consecutive days. Hematoxylin-eosin (HE), Masson staining to detect liver pathology and liver fibrosis; immunohistochemistry to detect CK19 and Ki67 to analyze the degree of hepatobiliary hyperplasia; qRT-PCR to detect gene expression of Il6, Tnfa, Il1b, Timp1, Tgfb and Col1 Status: Western blot was used to detect the activation of Akt/mTOR/NF-κB signaling pathway proteins.

　　Results Compared with the normal group, the liver of DDC model mice had a large number of inflammatory cell infiltration and significant bile duct hyperplasia, and the mRNA expression of factors related to inflammation (Il6, Tnfa and Il1b) and fibrosis (Timp1, Tgfb and Col1) were up-regulated. In the rapamycin treatment group, the liver inflammation and bile duct hyperplasia damage caused by DDC diet were significantly improved, and the mRNA levels of inflammation (Il6, Tnfa, and Il1b) and fibrosis (Timp1, Tgfb, and Col1) related factors were reduced. , Akt, mTOR and NF-κBp65 protein phosphorylation levels also decreased.

　　Conclusion Rapamycin may inhibit the Akt / mTOR/ NF-κB signaling pathway and improve DDC-induced primary sclerosing cholangitis in mice.