Abstract: Objective To study the effect of depletion of intrahepatic macrophages by clodronate liposomes on CCl₄-induced portal hypertension in rats. Methods Forty-eight male Wistar rats were randomly divided into two groups with 24 in each, and the rats in the model group were injected with olive oil and carbon tetrachloride (CCl₄) twice a week, respectively. At d₇₀, the rats in the two groups were further divided into two subgroups. The rats in one subgroup were injected with phosphate buffered solution liposomes (PL), and in the other were dealt with clodronate liposomes (CL) intravenously through tail veins once a week to remove intrahepatic macrophages. At d₁₀₅, the portal pressure in vivo was measured by BL-420F physiological function experiment system, the serum level of sCD163 was assayed by ELISA, and the positive expression of CD163 and inducible nitric oxide synthase (iNOS) in the liver tissues were detected by immunohistochemistry staining. Results In the control groups, serum level of sCD163 was (798.6±61.9) pg/L in CL injected rats, significantly lower than in the PL injected rats[(848.3±26.2) pg/L, P<0.05]; in the model groups, the liver coefficients and portal vein pressure in CL-treated rats were (4.7±0.8) and (10.6±2.0) mmHg, respectively, significantly lower than [(5.6±1.3) and (12.4±2.7) mmHg, P <0.05]in PL-treated rats; serum levels of ALT, AST and sCD163 in CL-treated rats were (69.9±21.4) U/L, (202.8±14.2) U/L and (980.1±122.3) pg/L, respectively, which were significantly lower than[(97.8±39.6) U/L, (290.6±168.1) U/L and (1083.2±97.2) pg/L, P<0.05]in PL-treated rats; the Results of immunohistochemistry showed that the expression of CD163 and iNOS protein in the liver tissues in CL-treated rats were weaker than those in PL-treated rats. Conclusion Hepatic macrophages is involved in the pathogenesis and development of portal hypertension, and needs further investigation.

Key words: Liver injury, Portal hypertension, Macrophage, Clodronate liposomes, Rats