|
|
|
维生素C和E提高大鼠在糖尿病培养基质中的胚胎抗氧化保护机制 BACKGROUND: Diabetes teratogenicity
seems to be related to embryonic oxidative stress and the extent of the
embryonic damage can apparently be reduced by antioxidants. We have studied
the mechanism by which antioxidants, such as vitamins C and E, reduce
diabetes-induced embryonic damage. We therefore compared the antioxidant
capacity of 10.5-day-old rat embryos and their yolk sacs cultured for
28h in diabetic culture medium with or without vitamins C and E. METHODS:
The embryos were cultured in 90% rat serum to which 2mg/ml glucose, 2mg/ml
beta hydroxy butyrate (BHOB) and 10&mgr;g/ml of acetoacetate were
added. Rat embryos were also cultured in a diabetic medium with 25&mgr;g/ml
of vitamin E and 50&mgr;g/ml of vitamin C. Control embryos were cultured
in normal rat serum with or without vitamins C and E. RESULTS: Decreased
activity of Cu/Zn superoxide dismutase (SOD) and of catalase (CAT) in
the "diabetic" embryos and their yolk sacs, and reduced concentrations
of low molecular weight antioxidant (LMWA) were found. Under these conditions
we also found a decrease in vitamin C and vitamin E concentrations in
the embryos, as measured by HPLC. In situ hybridization for SOD mRNA showed
a marked reduction of SOD mRNA in the brain, spinal cord, heart and liver
of embryos cultured in diabetic medium in comparison to controls. Following
the addition of vitamins C and E to the diabetic culture medium, SOD and
CAT activity, the concentrations of LMWA, the levels of vitamin C and
E and the expression of SOD mRNA in the embryos and yolk sacs returned
to normal. CONCLUSIONS: Diabetic metabolic factors seem to have a direct
effect on embryonic SOD gene and perhaps genes of other antioxidant enzymes,
reducing embryonic endogenous antioxidant defense mechanism. This in turn
may cause a depletion of the LMWA, such as vitamins C and E. The addition
of these vitamins normalizes the embryonic antioxidant defense mechanism,
reducing the damage caused by the diabetic environment. [引自Teratology 2001 Jul;64(1):33-44] |