[Effects of selenium supplement on atherogenesis of ApoE-knockout mice fed high fat diet].

OBJECTIVE: To investigate the effects of selenium supplement on atherogenesis and endothelial function in ApoE-knockout mice fed high fat diet. METHODS: ApoE-knockout mice fed with selenium-deficient and high fat diet were randomly allocated into 3 groups based on random number table including control group (not supplied with sodium selenite, n=10), low dosage selenium supplement group (supplied water with 0.1 mg/L sodium selenite, n=10) and high dosage selenium supplement group (supplied water with 0.2 mg/L sodium selenite, n=10). After 15 weeks, the following values were measured: the concentrations of selenium in heart and liver, the levels of serum lipid, the parameters of antioxidant function including activities of superoxide dismutase(SOD) and glutathion peroxidase (GSH-Px) and malondialdehyde (MDA) level in serum, the parameters of endothelial function including serum nitric oxide (NO), endothelin 1(ET-1), and vascular endothelial growth factor (VEGF) levels, and ET-1 and VEGF levels in aorta roots. The atherosclerotic lesions in aorta roots were analyzed with oil red O staining. RESULTS: (1) The selenium concentrations in heart and liver were significantly higher in high dosage and low dosage selenium supplement groups compared to control group (both P<0.05). (2) The levels of triglyceride, total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol and high-density lipoprotein cholesterol were similar among groups (all P>0.05). (3) The activity levels of serum SOD were significantly higher in low dosage ((113.8±12.5)U/ml) and high dosage selenium supplement group ((152.3±11.3)U/ml) compared to control group ((90.7±10.7)U/ml, all P<0.05). The activity levels of serum GSH-Px were significantly higher in low dosage ((53.9±7.2)U/ml) and high dosage ((69.6±8.7)U/ml) selenium supplement groups than that of control group ((36.4±5.6)U/ml, all P<0.05). The serum MDA levels in low dosage ((4.73±1.05)nmol/ml) and high dosage ((4.13±1.21)nmol/ml) selenium supplement groups were significantly lower than that of control group ((5.97±1.08)nmol/ml, all P<0.05). (4) The serum NO concentrations in low dosage ((61.5±12.8)µmol/L) and high dosage ((79.0±14.6)µmol/L)selenium supplement groups were significantly higher than that of control group((42.7±9.1)µmol/L, all P<0.05). The concentrations of serum ET-1 in low dosage ((52.8±6.3)ng/L)and high dosage ((46.3±4.7)ng/L)selenium supplement groups were significantly lower than that of control group((72.2±6.3)ng/L, P<0.05). The concentrations of serum VEGF in low dosage ((97.4±16.5)ng/L)and high dosage ((83.5±22.0)ng/L)selenium supplement groups were significantly lower than that of control group((125.8±18.6)ng/L, P<0.05). The expression levels of ET-1 and VEGF in aorta roots among low dosage and high dosage selenium supplement groups were significantly lower compared to control group (all P<0.05). (5) The plaque area of aorta roots in low dosage ((0.95±0.19)×10(5) µm(2))and high dosage selenium supplement ((0.75±0.15)×10(5) µm(2)) groups were significantly smaller than that of control group((1.13±0.23)×10(5) µm(2)), and the plaque area in high dosage selenium supplement group was significantly smaller than in low dosage selenium supplement group (P<0.05). CONCLUSION: Supplement of selenium can attenuate atherogenesis in ApoE-knockout mice fed high fat diet, which is possibly mediated via reducing lipid peroxidation and improving endothelial functions.

Hyperbaric oxygen therapy attenuates neuropathic hyperalgesia in rats and idiopathic trigeminal neuralgia in patients.

BACKGROUND: Neuropathic pain after nerve injury is severe and intractable, and current drug and non-drug therapies offer very limited pain relief. Hyperbaric oxygen (HBO 2) has been clinically used for protection of the nervous system after acute injury. We investigated whether HBO 2 treatment could prevent and/or attenuate neuropathic pain in animals and in patients. METHODS: Mechanical allodynia and thermal hyperalgesia and neurochemical alterations of neuropathic pain were analysed in male, adult, Sprague-Dawley rats with sciatic nerve injury. Clinical trials were conducted in patients with idiopathic trigeminal neuralgia. RESULTS: Repetitive HBO 2 treatment [a combination of pressure at 3 atmosphere absolute (ATA) and pure oxygen] greatly inhibited behavioural signs of neuropathic pain manifested as thermal hyperalgesia and mechanical allodynia. Such an HBO 2 treatment also inhibited nerve injury-induced induction of c-Fos and activation of astrocytes and increased phosphorylation of NR2B receptor and the subsequent Ca 2+-dependent signals in rats. Neither high pressure (up to 3 ATA) nor pure oxygen alone resulted in analgesic effect. In clinical trials, one course of HBO 2 therapy (10 consecutive days) produced a rapid-onset, dose-dependent and long-lasting analgesic effects evidenced by the decreased doses of carbamazepine required for keeping patient pain at a minimum and decreased scores of visual analogue scales, which was used for patient's self-evaluation. CONCLUSIONS: These findings support that HBO 2 therapy is an effective approach for treating neuropathic pain in both animals and human beings and suggest that neural protection, anti-inflammation and inhibition of nerve injury-induced altered neural activity may contribute to the analgesic effect of HBO 2 therapy.