Effects of low molecular weight heparin on newborn mouse liver cells congenitally infected with human cytomegalovirus / 中华传染病杂志

ABSTRACT

Objective To explore the effects of low molecular weight heparin (LMWH) on the virological and pathological changes of newborn mouse liver congenitally infected with human cytomegalovirus (HCMV).Methods Sixty healthy pure line clean level BALB/c mice which were about 10 weeks old (half were female) were divided into five groups (six pairs in each group).The mice in LMWH intervention group and positive control group were intraperitoneally inoculated with 6.0 lg tissue culture infective dose50 (TCID50) of HCMV AD169; those in blank control group were intraperitoneally injected with 0.5 mL dulbecco's modified Eagles medium (DMEM) ; then all the mice were paired to mate.The pregnant mice in LMWH intervention group Ⅰ were subcutaneously injected with LMWH 1000 U/kg daily for 10 days; those in group Ⅱ were subcutaneously injected with LMWH 1000 U/kg daily for 5 days and their newborn mice were subcutaneously injected with LMWH 1000 U/kg daily for 5 days; those in group Ⅲ were subcutaneously injected with LMWH 1000 U/kg daily for 10 days in their newborn mice.All these newborn mice were sacrificed at day 10 of birth.The liver was removed for virus isolation,dry-wet weight determination,pathology examination and quantitative fluorescence-polymerase chain reaction (PCR) detection.The comparison among groups was done by analysis of variance.Results HCMV was isolated from the supernatant of liver tissue homogenate in 10-day positive control newborn mice,while HCMV was isolated in 24-day newborn mice of the other three groups of LMWH intervention.Pathology confirmed that positive control liver tissue had inflammatory changed,liver cell inflammatory swelling degeneration,vacuoles degeneration,specific HCMV inclusion body in nuclear,and portion of liver cell necrosis,while liver pathological results of LMWH intervention group showed mild liver cell inflammatory changes and slight cell inflammatory swelling degeneration,which were similar to the blank control group.The moisture of liver tissue contents in LMWH intervention group decreased more obviously than positive control group.The HCMV DNA loads in 50 mg liver tissues of LMWH intervention groups Ⅰ,Ⅱand Ⅲ were (3.26±0.43),(3.26±0.41) and (3.32±0.51) lg copy,respectively,which were significantly lower than that of positive control group [(7.38 ± 0.53) lg copy; F =314.620,P0.01],while there were no significant differences among LMWH intervention groups (P＞0.05).Conclusion LMWH intrauterine and postnatal interventions can significantly reduce HCMV DNA replication in hepatocytes,and relieve inflammatory changes in liver tissue.