| Objective In previous studies, HBV DNA level in maternal serum was an impotent factor for intrauterine infection; Lamifudine(STC) and interferon a (IFN a ) are clinically employed extensively now, and their antiviral effect is good, but they were categarized as grade C in the use of drugs during pregnancy, whose application for pregnant women or animals has not been studied, which prevented using of them durings pregnancy. So in this study supported by the National Nature Science Foundation of China (No.30070668), the transgenic mice with high levels of hepatitis B virus were employed for the first time to study the antiviral effect of 3TC and IFN a during the different gestation, and the change of serologic HBV markers were detected. At the same time, the effects of perinatal exposure to antiviral drugs on the mother and offspring were observed. We try to probe into the efficacy of two anti-HBV drugs for decreasing the amount of HBV DNA in maternal blood and the safety of mother and offspring, and provide some animal experiment basis for the use of two drugsin antiviral therapy of HBsAg positive mother during pregnancy, especially those in early pregnancy by evaluating the efficacy and safety of 3TC and IFN a therapy. In additon, we try to probe initially into the possibility of HBV transgenic mice as an animal model for study of HBV intrauterine infection. Methods:1. One-cell mouse embryos were collected from the super ovulated Kunming mice, and perfect embryos were randomly allocated into experiment groups and control group depending on various concentration of 3TC and IFN a , then embryos were cultured in micro drops of medium for 72 hours. The effects of 3TC and IFN a in various concentrations on development of embryos were observed.2. Twenty-one HBV transgenic female mice with steady expression of high-level HBsAg were randomly allocated into 3 groups: experiment group 1, experiment group 2 and control group. Mice in experiment group 1 received 3TC 100mg kg-1 d-1 from pregnancy day 5 to delivery, Mice in experiment group 2 received the same dosage of 3TC from pregnancy day 10 to delivery, and mice in control group received normal saline 0. 5ml d-1 from pregnancy day 5 to delivery. At the same time, 12 C57BL/6J female mice were randomly allocated into 2 groups (experiment group and control group of common mice) for observing the possible difference in some observed markers between HBV transgenic mice and common mice.3. Another twenty-one HBV transgenic female mice and 12 C57BL/6J female mice were randomly chosen for studying effectof IFN (5MU m-2 per two day). The grouping method was the same as that of 3TC.4. HBsAg and HBV DNA content before and after the treatment in the mouse sera were analysed by using RIA and HBV fluorescence PCR.5. Daily observations of the pregnant mice during pregnancy were performed, and delivery was observed 24h a day. On pregnant day 19, 3 mice from every group were randomly chosen for complete necropsy. The index that showed the situation of procreate, such as the number of luteal, the average weight of placenta and fetus were recorded; the rate of dead fetus and the rate of maternal dead fetus (the number of mice that had dead offspring/ the number of all pregnant mice) were calculated and statistically analyzed; The organ weight and organ coefficient were recorded, and the main organ structure of every mouse was examined by histological observation and immunohistochemical method.6. Abnormalities of live fetus were investigated by examining their appearance, gut and skeleton. Live pups were counted, and the postnatal survival was statistically analyzed. The data on developmental performance such as weight gain, activity, the time of opening the eyes or ears and emergence of hair were observed. Drug effects on adult mice and offspring were assessed.7. One month after delivery, HBV DNA and HBsAg in the newborn mice sera were detected. The placental tissue was collected to detect HBsAg in the cells by immunohistochemical method. Results:1. Compar...
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