Chemically modified hepatic stellate cell selective carrier mannose‐6‐phosphate carrying salvianolic acid B alleviates liver fibrosis in vivo

2019 
: Our study aimed to explore the effects of a new synthetized hepatic stellate cell selective carrier mannose-6-phosphate modified salvianolic acid B (M6P-SAB) on liver fibrosis. Liver fibrosis model was firstly induced by 4-week injection of dimethylnitrosamine. Afterwards, liver fibrosis rats were divided into six groups: model group, γ-interferon (γ-IFN) group, SA-B group, M6P-SAB high-dose group, M6P-SAB medium-dose group, and M6P-SAB low-dose group. After 4-week drug administration, liver specimens were collected for haematoxylin-eosin (HE) and Sirius red staining. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), and total bilirubin (TBiL) were detected by a biochemical auto-analyzer. Meanwhile, hydroxyproline contents in liver tissue were also measured. Mortality rates of model group, γ-IFN group, SA-B group, M6P-SAB high-, medium- and the low-dose group were 15%, 55%, 20%, 10%, 5%, and 20%, respectively. Spleen weight and spleen weight/body weight ratio of M6P-SAB high-, medium- and low-dose groups were lower, and liver weight and liver weight/body weight ratio of were increased. Serum ALT, AST and TBiL levels of M6P-SAB high-, medium- and low-dose groups were significantly lower. Reduced hydroxyproline contents in liver tissue were observed in SA-B group, as well as M6P-SAB high-, medium- and low-dose groups. Moreover, liver fibrosis reversed obviously in SA-B group and M6P-SAB high-, medium- and low-dose groups according to the HE and Sirius red staining. M6P-SAB has the ability to alleviate fibrosis in vivo, suggesting that it might be a promising drug in the clinical treatment of liver fibrosis.
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