动物造模,原发性硬化性 z-bio 2023-03-15 580

　　Objective To investigate the therapeutic effect of rapamycin on 3,5-diethoxycarbonyl 1,4-dihydrocollidine (DDC)-induced mouse primary sclerosing cholangitis (PSC), and to 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 group and a DDC model + rapamycin (RAPA) treatment group. Pamycin (5 mg/kg body weight) was injected once a day for 7 consecutive days. Hematoxylin-eosin (HE) and Masson staining were used to detect liver pathology and liver fibrosis; immunohistochemistry was used to detect CK19 and Ki67 to analyze the degree of hepatic bile duct hyperplasia; qRT-PCR was used to detect the expression of Il6, Tnfa, Il1b, Timp1, Tgfb and Col1 genes Activation of Akt/mTOR/NF-κB signaling pathway protein was detected by Western blot.

　　Results Compared with the normal group, the DDC model mice had a large number of inflammatory cell infiltration and significant bile duct hyperplasia in the liver, and the mRNA expressions of inflammation (Il6, Tnfa and Il1b) and fibrosis (Timp1, Tgfb and Col1) related factors were up-regulated. In the rapamycin-treated group, DDC diet-induced liver inflammation and bile duct proliferative injury were significantly improved, and the mRNA levels of inflammation (Il6, Tnfa, and Il1b) and fibrosis (Timp1, Tgfb, and Col1)-related factors were decreased. , Akt, mTOR and NF-κB p65 protein phosphorylation levels were also reduced.

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