Injured effect of hyperhomocysteinemia and asymmetric dimethylarginine on rats cerebral vascular and efficacy of combined drug regimens
10.3760/cma.j.issn.0254-9026.2014.06.026
- VernacularTitle:高同型半胱氨酸和非对称性二甲基精氨酸对大鼠脑血管的影响及干预的研究
- Author:
Ling LI
;
Lin WANG
;
Xin LI
;
Xiaoshuang XIA
;
Yongle LI
- Publication Type:Journal Article
- Keywords:
Cysteine;
Arginine;
Cerebrovascular circulation
- From:
Chinese Journal of Geriatrics
2014;33(6):653-656
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the damage of hyperhomocysteinemia (HHcy) and asymmetric dimethylarginine (ADMA) on the structure of rats cerebral vessels,and to explore the treatment effect of probucol,folic acid and vitamin B12.Methods Totally,70 male Sprague-Dawley(SD) rats were randomly divided into seven groups:normal control (A),HHcy model (B),low-dose-probucol (C),middle-dose-probucol (D),high-dose-probucol (E),folic-acid plus vitamin B12 (F),folic-acid plus vitamin B12 plus probucol(G)group.Group A was fed plain feedstuff and water.Other groups were fed homomethionin feedstuff and water,probucol (340,510,680 mg· kg-1 · d-1),folic acid and vitamin B12,folic acid plus vitamin B12 plus probucol respectively.The plasma concentrations of homocysteine(Hcy) and ADMA were assayed by high-performance liquid chromatography method (HPLC) at the beginning,and at the end of 8 and 12 weeks.The analysis of rats cerebral vessels was performed with electron microscope at the end of 12 weeks.Results (1) After adding high concentrations of methionine feedstuff for 8 weeks,the levels of Hcy in group B (60.4±11.9) μmol/L were significantly raised compared with group A(7.1±1.4) μmol/L.Meanwhile,ADMA levels in group B(1.3±0.4)μmol/L were higher than group A(0.4±0.1) μmol/L.At the end of 12 week,the levels of Hcy and ADMA were lower in groups C[(49.9±11.4)μmol/L,(1.0±0.2)μmol/L],D [(46.8± 10.9)μmol/L,(0.9±0.1)μmol/L],E[(44.3±11.4)μmol/L,(0.9±0.1)μmol/L],F [(16.3 ± 4.9)μmol/L,(0.7 ± 0.2)μmol/L] compared with group B [(69.5 ± 11.4)μmol/L,(1.6 ±0.5)μmol/L],but higher than group A[(6.7±1.3)μmol/L,(0.5±0.1)μmol/L].The levels of Hcy and ADMA in group G[(8.9±1.9) μmol/L,(0.6±0.2) μmol/L]were also lower than those in group B (P<0.05],but they did not show statistically significant differences compared with group A(P>0.05).(2) According to correlative analysis,Hcy levels were positively correlated with ADMA levels (P<0.05).(3) On electron microscope,we observed that the cerebral artery and cerebral cortex of group B were seriously damaged.After the intervention with probucol,folic acid and vitamin B12,the structure of rats cerebral vessels were improved in group C,D,E,F and G as compared with group B,and group G were especially improved more obviously.Conclusions The HHcy and ADMA could damage the structure of rats cerebral vessels.Probucol,folic acid and vitamin B12 may alleviate the cerebral vascular damage by decreasing the levels of Hcy and ADMA,and the effect is more significant by the combined drug regimens of Probucol,folic acid and vitamin B12.