The Experimental Research On The Expression Of ICAM-1, ENOS In The Brain Of Rats With Hyperhomocysteinemia And After The Intervention Of B Vitamins

Objective: to observe the effct of Hhcy on the expression of ICAM-1 and eNOSin the brain of rats and the intervention of folic acid, Vitamins B12 and Vitamins B6 onit by inducing Hhcy model of rats.Methods: 40 healthy male Sprague-Dawley rats aged 4 weeks were divided into4 groups as:normal group, model group, interventional groupl, interventional group2by the way of randomized block design(by weight). There were 10 rats in each group.The rats in the normal group were fed with common diet and intragastricadministration with water for 12 weeks; the rats in the model group were fed withhigh concentration of methionine(Met) diet(1%) and intragastric administration withwater for 12 weeks; the rats in the interventional group1 were fed with highconcentration of Met diet and intragastric administration with water for 4 weeks, thenfed with high concentration of Met diet and intragastric administration with folic acid,Vitamin B12 and Vitamin B6 in the following 8 weeks; the rats in the interventionalgroup2 were fed with high concentration of Met diet and intragastric administrationwith folic acid, Vitamin B12 and Vitamin B6 for 12 weeks. The plasma totalhomocysteine(tHcy)levels were assayed by high-performance liquid chromatographymethod(HPLC) at the end of 0, 4th and 12th week. The expression of intercellularadhesion molecule-1 (ICAM-1) and endothelial nitric oxide synthase(eNOS) weredetected by immunohistochemical method in the cerebral vessels and brain tissue ofrats. Results:1. The contiontration of plasma tHcy in the different time: In the normal group,the contiontration of plasma tHcy were 12.19±2.55μmol/L, 11.66±53.74μmol/L, and13.27±3.63μmol/L respectively at the end of 0, 4th and 12th week, there were nostatistical difference (P＞0.05). At the end of 0 week, the plasma tHcy levels of 4groups were 12.19±2.55μmol/L, 13.19±3.10μmol/L, 13.37±3.18μmol/L and12.75±3.26μmol/L respectively, there were no statistical difference (P＞0.05). At theend of 4th week, the plasma tHcy levels of model group and interventional group1(22.85±4.92μmol/L and 21.01±6.55μmol/L) were significantly higher than normalvalue7.10～18.62μmol/L (P＜0.01). The Hhcy model were induced successfully. Atthe end of 12th week, the plasma tHcy levels of model group(20.76±5.49μmol/L)were significantly higher than those of normal group(P＜0.01), which is no statisticaldifference from those(22.85±4.92μmol/L) at the end of 4th week(P＞0.05). At the endof 12th week, the plasma tHcy levels of interventional groupl (10.28±5.05μmol/L)were apparently lower than those (21.01±6.55μmol/L) at the end of 4th week(P＜0.01),which is no statistical difference from those of normal group and those at thebeginning(P＞0.05). At the end of 4th week, the plasma tHcy levels of interventionalgroup2(16.40±4.15μmol/L) were higher than those of normal group and those at theend of 0 week (P＜0.05), lower than those of model group and interventional group1 inthe same time(P＜0.05); at the end of 12th week, the plasma tHcy levels ofinterventional group2 (10.20±2.25μmol/L)were apparently lower than those at the endof 4wk(P＜0.01), which is no statistical difference from those of normal group andthose at the end of 0 week(P＞0.05).2. The expression of ICAM-1 in the cerebral vessels: the number of masculinecerebral vessels in the 4 groups were 0.35±0.31, 3.23±0.88, 1.54±0.36 and 0.98±0.23respectively, there were significantly statistical differences between the number ofmasculine cerebral vessels in the 4 groups(P＜0.01). The sequence is model group＞interventional group 1＞interventional group2＞normal group. 3. The expression of ICAM-1 in the brain tissue: the rate of masculine cells in the4 groups were 0.2637±0.0254, 0.6056±0.0481, 0.4476±0.0338 and 0.3765±0.0249respectively, there were significantly statistical differences between the rate ofmasculine cells in the 4 groups(P＜0.01). The sequence is that model group＞interventional groupl＞interventional group2＞normal group.4. The expression of eNOS in the cerebral vessels: the number of masculinecerebral vessels in the 4 groups were 0.4300±0.0320, 0.2675±0.0371, 0.3513±0.0284and 0.4137±0.0145 respectively, there were no statistical difference between thenumber of masculine cerebral vessels in the normal group and interventionalgroup2(P＞0.05), but there were significantly statistical differences between the restgroups(P＜0.01). The sequence is that interventional group2, normal group＞interventional group1＞model group.Conclusions: The expression of ICAM-1 were increased in the cerebral vesselsand brain tissue of rats with Hhcy. Inversely, the expression of eNOS were decreasedin the cerebrovascular of rats with Hhcy. The intervention of B Vitamins coulddecrease the contiontration of plasma tHcy effectively, could reduce the expression ofICAM-1 and increase the expression of eNOS to some degree.