The Research In Effect And Mechanism Of Hype-rhomocysteinemia On The Blood-Brain Barrier Of Rats

Objective:To investigate Hyperhomocysteinemia(Hhcy)-induced the pathogenesis of the blood-brain barrier(BBB) permeability in rats.Methods:Forty Sprague-Dawley rats were randomly divided into two groups,including the control group and Hhcy model group.Plasma total homocysteine(tHcy) and serum nitric oxide(NO) of two groups were detected in the beginning and 24th week of the experiment.Both of the control group and Hhcy model group were divided into two groups in the 24th week of the experiment again.The lever of evans blue of brain and serum superoxide dismutase(SOD)and serum malondialdehyde(MDA) in one group of them were detected in the 24th week of the experiment.The lever of water content of brain were detected and ultramicrostructure of BBB were observed in the another group at the same time.Results:1.The comparison of plasma tHcy in the different time:The level of plasma tHcy in Hhcy group and control group were(13.19±3.10)μmol/L vs(13.37±3.18)μmol/L at the beginning of the experiment(P>0.05),while they were(22.51±4.47)μmol/L vs (13.92±4.16)μmol/L in the 24th week of the experiment(P<0.05).2.The comparison of serum nitric oxide in the different time:The level of serum nitric oxide in both of Hhcy group and control group were(28.44±8.86)μmol/L vs (27.11±7.81)μmol/L in the beginning of the experiment(P>0.05),while they were (12.74±5.73)μmol/Lvs(27.13±5.85)μmol/L in the 24th week of the experiment.3.The result of evans blue of brain of two groups:Evans blue in Hhcy group[(7.37±1.07)μg/g]was significantly higher than that in the control group[(5.90±0.46)μg/g, (P<0.05)].4.The result of water content of brain of two groups:Water content of brain in the Hhcy group(78.10%±0.31%) was significantly higher than that in the control group (74.93%±0.28%,P<0.05).5.Ultrastructural alterations of BBB:Electron microscopic features the cerebral capillary wall of control group had a normal appearance.Capillary alterations induced by a homocystine diet as follows:microvascular fibrosis,local thickening of the basement membrane,an abnormal electronlucent structure indicating perivascular amorphous fibrosis was observed within the basement membrane.6.The serum superoxide dismutase levels of the Hhcy group[(214.21±11.52)U/ml] was lower than that of the control group[(310.30±22.48)U/ml]in the 24th week of the experiment(P<0.05).7.The serum malondialdehyde levels of the Hhcy group[(7.50±1.72)nmol/L]is higher than that of the control group[(4.08±0.45)nmol/L]in the 24th week of the experiment(P<0.05).Conclusion:The patho-model of rats with hyperhomocysteinemia were constructed by feeding homomethionin diets,while controlled rats were fed normal diets.Hhcy may increase the level of evans blue of brain and water content of brain of rats.Electron microscopic features the basement membrane and capillary endothelium alterations. These results demonstrated that Hhcy increase the permeability of BBB in rats, meanwhile the level of serum nitric oxide and serum superoxide dismutase of Hhcy group were significantly lower than that of control group.It illustrated that the mechanism of Hhcy increase the permeability of BBB maybe correlate with endothelial dysfunction with decreased nitric oxide bioavailability.