动物造模,原发性硬化性胆管炎 z-bio 2022-12-14 328

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

　　Methods Female C57BL/6J mice aged 6-8 weeks were randomly divided into normal diet group, DDC diet (0.1% DDC) modeling group and DDC modeling+rapamycin (RAPA) treatment group. Rapamycin (5 mg/kg body weight) was intraperitoneally injected once a day for 7 days. Hematoxylin eosin (HE) and Masson staining were used to detect liver pathology and degree of liver fibrosis; CK19 and Ki67 were detected by immunohistochemistry, and the degree of hepatobiliary duct hyperplasia was analyzed; The expression of Il6, Tnfa, Il1b, Timp1, Tgfb and Col1 genes were detected by qRT PCR; Western blot detection Akt/mTOR/NF- κ B signal pathway protein activation.

　　Results Compared with the normal group, the liver of DDC model group mice had a large number of inflammatory cells infiltration and significant bile duct hyperplasia, and the mRNA expression of inflammation (Il6, Tnfa and Il1b) and fibrosis (Timp1, Tgfb and Col1) related factors was up-regulated. In the rapamycin treatment group, the hepatitis response and bile duct proliferative injury of mice induced by DDC diet were significantly improved, the mRNA levels of inflammation (Il6, Tnfa and Il1b) and fibrosis (Timp1, Tgfb and Col1) related factors were decreased, and Akt, mTOR and NF- κ The phosphorylation level of Bp65 protein also decreased.

　　Conclusion Rapamycin may inhibit Akt/mTOR/NF- κ B signal pathway to improve DDC induced primary sclerosing cholangitis in mice.