Biological changes of Kupffer cells in response to suppression of discoidin domain receptor 1 by in vivo delivery of small interfering RNA following acute hepatic injury / 中华创伤杂志

ABSTRACT

Objective To investigate the effect of small interfering RNA (siRNA) suppressing discoidin domain receptor 1 (DDR1) gene on biological behaviour of Kupffer cells (KC) in acute hepatic injury. Methods Male BALB/c mice were randomly divided into control, hepatic injury model, non-silencing siRNA and DDRlsiRNA groups. Hepatic injury model induced by intravenous injection of Con-canavalinA (ConA) 15 mg/kg, with or without hydrodynamic tail intravenous injection of naked siRNA (50 μg,2.0-2.5 mg/kg)/mouse or 1.5 ml normal saline. The expression of DDRI was assayed by West-ern blot and pro-inflammatory cytokine expression analyzed by ELISA. In the meantime, alanine amin-otransferase (ALT) and Kupffer cells'clearance to carbon granules was detected. Results The expres-sion of DDR1 obviously increasod at 6 h after hepatic injury, roached peak at 24 h and began to decrease at 48 h. Pretreatment with DDRisiRNA could obviously inhibit the expression of DDR1 and abrogate the high levels of ALT, expressions of TNF-α and IL-1β as well as phagocytosis of Kupffer cells. Conclu-sions Inhibition of discoidin domain receptor 1 by in vivo delivery of siRNA attenuates ConA-induced hepatic injury. Possible mechanism is that the inhibition of activity of KC inhibits the expression of pro-in-flammatory cytokines and thus alleviates hepatic injury.