| Objects: 1)to establish a relatively stable hyperuricemia model in rats;2)to observe pathological changes of Aorta in hyperuricemia rats model;3)to study effect and mechanism of hyperuricemia on permeability of blood brain barrier in rats.Methods: 1)60 adult male SD rats were randomly divided into 6 groups.2)The first group(control group)was given the same dose of distilled water per day as experimental groups;the second group was given 20 mg/kg yeast extract and 300mg/kg potassium oxonate every day;the third group was given 20 mg/kg yeast extract and 300mg/kg potassium oxonate every day,fourteen days later,potassium oxonate was increased 50mg/kg every two week;the fourth group was given 20 mg/kg yeast extract and 300 mg/kg potassium oxonate every day,fourteen days later,potassium oxonate was increased 50mg/kg every week;the fifth group was given 20 mg/kg yeast extract and 300 mg/kg potassium oxonate every day,fourteen days later,potassium oxonate was increased 100 mg/kg every two weeks;the sixth group was given 20 mg/kg yeast extract and 300 mg/kg potassium oxonate every day,fourteen days later,potassium oxonate was increased 100 mg/kg every week.All groups rats were killed thirty five day latter.3)Rats were weighed and observed every day.4)Rats were take blood by the left and right can thus venous alternately every week and serum was separated to detect uric acid(UA)and nitric oxide(NO).5)Rats were sacrificed after the last blood collection to separate brain tissue and blood vessels,which were used for observation of ultra structure of blood-brain barrier(BBB)and HE staining separately,Injection of Evans blue(EB)by intravenous to observe permeability of BBB.Results:(1)The levels of serum UA in group Ⅱ,Ⅱ,Ⅱ,Ⅱand Ⅵreached to peak sat the 14 th day and were significantly higher than group Ⅰ,there was no significant difference between five experiment all groups.At the 21 st day,the serum UA levels of groupⅡ,Ⅱ,and Ⅱ Ⅵcontinued to rise and were significantly higher than groupⅡ.At the 28 th day,the levels of serum UA in groupⅡ,Ⅱ,Ⅱand Ⅱshowed a slight decrease and were still significantly higher than control group,but the serum UA of group Ⅵstill continued to rise.;The serum UA levels in group Ⅱ,Ⅱ,and Ⅱ Ⅱcontinued to decreased at the 35 th day and were similar to control group,but the serum UA of group was still higher than control group.Ⅵ(2)The levels of serum NO at baseline time were similar between every groups,however,the levels of serum NO in experiment groups were significantly lower than control group at the 35 th day.(3)There was no significantly difference in Evans blue(EB)content between groupⅠ,Ⅱ,and Ⅱ Ⅱ,The levels of EB content in group and Ⅱ Ⅵwere significantly higher than the other groups.(4)There was no obvious pathological changes in group Ⅰ.Compared with control group,the vascular injury in the hyperuricemia group were intimal layer thickening,degeneration and derangement of smooth muscle cells of middle layer and poor serous layer structure.The higher serum UA injury vascular more serious.(5)There was no obvious pathological change of brain capillary wall in control group.The BBB in group II,III and IV was slightly altered including local basement membrane thickening and partial mitochondrial double layer membrane was destroyed.In group V endothelial cells were dropsy;the number of organelles decreased;vacuoles,liquefied vesicles and vesicular structures were formed in cytoplasm and lots of blank electronic regions were formed around neurons.In group VI the morphology and structure of capillary wall were thickened,foot process of glial cells were edema,neurons nuclear membrane were thickened and partially dissoluted.Conclusion:(1)Administration of yeast extract combined with potassium oxonate could make a stable rats hyperuricemia model;(2)Serum hyperuricemia in rats could cause damage to BBB endothelial cells and basement membrane structure and lead BBB permeability increase;(3)BBB damage was associated with decreased NO level and cerebral micro vascular diastolic function. |
