The Study Of The Mechanism Of The Role Of NOS In Fetal Hypoxic Ischemic Encephalopathy Induced Intrauterine Distress

Objective: Evaluating the relationship of NOS and the morphologic changes of fetal rat brain when intrauterine distress and the protective role of NOS inhibitors. Methods:(1)Set up fetal rat intrauterine distress model. (2) Divide into the control group, acute ischemia group,treating group 1 (injecting L-NNA 4mg/kg in pregnant rat's abdomen before ischmia.), reperfusion group, treating group 2 (injecting L-NNA 4mg/kg in pregnant rat's abdomen before ischemia and injecting AG 500mg/kg before operation).(3) Observing the changes of mitochondria by using transmission electron microscope. Measuring the expression of nNOS mRNA and the activity of iNOS and the range of cerebral ischemia. Observing the pathologic changes of the fetal rat hypoxic ischemic encephalopathy when intrauterine distress through light microscope. Results:(1)The OD of nNOS in acute ischemia group and treating group1(5/15/30min) is obviously higher than that of the control group(P<0.05).The OD of nNOS in treating group1(5/15min) are lower than those of acute ischemia group(P<0.05). There is no different between the OD of nNOS(30min) in treating group1 and that in acute ischemia group(P>0.05). The activity of iNOS in reperfusion group and treating group2(6/12/24h) is higher than that of the control group(P<0.05). The activity of iNOS in reperfusion group(6/12/24h) are higher than those in treating group2(P<0.05).(2)The range of cerebral ischemia in acute ischemia group and treating group1(5/15/30min) is larger than that in the control group(P<0.05). The range of cerebral ischemia in treating group1(5/15min) are smaller than those in the acute ischemia group(P<0.05). There is no different between the range of cerebral ischemia(30min) in treating group1 and acute ischemia group(P>0.05).The range of cerebral ischemia in reperfusion group(6/12/24h) are smaller than those in acute ischemia group. The time of reperfusion longer ,the range of cerebral ischemia smaller. The range of cerebral ischemia in treating group2(6/12/24h) are smaller than those in reperfusion group(P<0.05). (3) Mitochondria Rsv in acute ischemia group and treating group1(5/15/30min) is smaller than that in the control group(P<0.05). Mitochondria Rsv in treating group1(5/15min) are larger than those in acute ischemia group(P<0.05). There is no different between mitochondria Rsv in acute ischemia group and treating group1(30min). Mitochondria Rsv in reperfusion group and treating group2(6/12/24h) is smaller than that in the control group(P<0.05). Mitochondria Rsv in treating group2(6/12/24h) are larger than those in reperfusion group(P<0.05). Conclusion:(1)The fetal rat intrauterine distress model in the study is easy to operate. The model's mortality and miscarriage rate are lower. The established model was in conformity with the characteristics of the pathologic changes of the fetal rat hypoxic ischemic encephalopathy when intrauterine distress.(2)nNOS mediates fetal rat cerebral ischemia and the changes of mitochondria structure during early intrauterine distress.After acute ischemia 30min, nNOS'neurotoxic is not the most important in fetal rat hypoxic ischemic encephalopathy. There is other mechanisms in fetal rat hypoxic ischemic encephalopathy. (3)iNOS mediates fetal rat cerebral ischemia and the changes of mitochondria structure when reperfusion following ischemia. (4) L-NNA play a preventive role in acute fetalhypoxic-ischemic brain damage when intrauterine distress, but effect is limited. AG play a obvious protective role in brain damage when reperfusion following ischemia.