| Objective To detect the neural tube defects teratogenicity effects of cyclophosphamide and mechanism on rats, observe protective effects of soybean isoflavones coordinated with folic acid and the best coordinate dose. MethodsPart One: Pregnant rats were randomly divided into control and fourexperimental groups according to their body weight, Cyclophosphamide intakes among five groups were 0,7.5,10.5,12.5,15.0mg/kg vja intraperitoneal administration on the 13th day of gestation. On the 14th day of gestation, three rats were randomly executed and embryos were checked through optical microscopy and transmission electron microscopy; the other rats were executed on the 20th day of gestation, the biochemical indices including SOD, MDA, NO and tissuse slice were examined for pathological observation, the skeleton exemplars were prepared besides the morphological changes of the embryos were recorded.Part Two: The pregnant rats were randomly divided into six groups, the intakesamong six groups were cyclophosphamide 12.5mg/kg, folic acid 0.7mg/kg, folic acid with soybean isoflavones 20,40,80,160mg/kg, cyclophosphamide were given via intraperitoneal administration on the 13th day of gestation while folic acid and soybean isoflavones were given via mouth during the whole gestation course. Theexamined indices were the same to the part one. Part Three: Primary corticalneurons were cultured and cyclophosphamide was added to neuronal preparations after 48 hours, All biological indices described above were observed under Phase-contrast microscopy, flow cytometry and single-cell gel electrophoresistechnology after 24 hours. Part Four: As normal control group, the method ofcyclophosphamide added was the same to part three, folic acid and geinstein was added to neuronal preparation in vitro with different concentration(folic acid50mg/L, folic acid with geinsteinl3.5,27,54mg/L et al)during the wholeprocession. Results Part One: 1.The frequency of abnormalty, skull defecs ofembory and MDA, NO in serum of pregnant rats had significantly positive correlation with the intake of cyclophosphamide; while SOD had significantly negative correlation ; 2. Many meningomyelocele embryos turned up in modle-making groups; 3. The frequency of abnormalty increased with the rising of cyclophosphamide intake; 4. The developmental index of embryoes significantly decreased compared with the control group; 5. Optical microscopy results indicate that a lot of nucleus were wrecked and condensed; 6. Under transmission electron microscopy , apoptotic cells exhibited typical morphological changes, including irregular shape of nucleus, chromatin condensation.Mitochondria was impairedand indistinct nuclear membranes et al. Part Two: l.The SOD activitiesincreased while MDA> NO declined in every prevention groups , the changes showed dose-effect response relationship with soybean isoflavones; 2. The frequency of abnormalty, skull defecs of embories decreased, moreover there was the best effect in the group of folic acid coordinate with soybean isoflavones40mg/L ; 3. The developmental index of embories significantlyimproved compared with the model-making group; 4. Under optical microscopy and transmission electron microscopy, the nucleus and the organdies were notsignificantly damaged or the impairment were diminished. Part Three: 1. Theneuroepithelial cells in dispersed cell culture started to extend several neurites within several hours after plating. These neurites differentiated into an axon and several dendrites, and forming an extensive network.. In the group treated with cyclophosphamide ,the floating cells increased in number, the neurites were shorten or lost, and the survival cells decreased in number, and the networks of cell processes were sparse; 2.In the model group, apoptotic peak and "comet cells" was found .Part Four: In the groups treated with geinstein and folic acid, AP and the number of "comet cells" declined.Moreover, the best result was obser...
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