Study On Investigatation Of Oxidative Stress, Inflammation Reaction, Endothelial Cell Dysfunction And The Mechanisms Of N-acetylcysteine Intervention In Rats With Chronic Intermittent Hypoxia

Partâ… To study on investigation of the oxidative stress, inflammation reaction, and endothelial cell dysfunction in rats with chronic intermittent hypoxia.[OBJECTIVE] To investigate the oxidative stress, inflammation reaction and endothelial cell dysfunction in rats with chronic intermittent hypoxia .[METHODS] To establish a chronic imtermittent hypoxia(CIH) animal model in rats , in order to mimic the intermittent hypoxia of obstructive sleep apnea-hypopnea syndrome (OSAHS) in humans. 24 healthy male SD rats were randomly assigned to two equal groups: the control group and the CIH group. The rats in CIH group were placed in an animal chamber subjected to chronic imtermittent hypoxia (nadir ambient oxygen concentration 6-7 %, maximum ambient oxygen concentration 20-21 %, Continuing respectively to 5-7 second) for 8 hours per day (from 9AM to 5PM) and the experimental lasted for 35 days. The rats in control group were placed in the same animal chamber without chronic imtermittent hypoxia. After the experiment. We measured the level of 8-iso-PGF₂α, MDA, IL-6, TNF-α, VEGF and ET-1 in plasma by ELISA. Western blot were performed to study the expression of NF-кB in rat lung specimens. HIF-1αand MMP-9 mRNA expressions and microscopic examination were detected in lung tissues.[RESULTS] The weight of rats in CIH group were lighter than in control group, 352.85±39.08g vs 411.24±17.32g respectively (P<0.05); the concentration of 8-iso-PGF₂α, MDA, IL-6, TNF-α, VEGF and ET-1 in plasma in CIH group was higher than that in control group, 373.80±83.44 vs 223.80±77.19 pg/mk 17.00±5.79 vs 8.97±4.93 pg/mk 138.63±43.82 vs 41.82±5.24 pg/mk 126.62±34.81 vs 73.43±5.72 pg/mk 101.08±27.55 vs 52.14±5.68 pg/ml and 17.80±4.35 vs 12.04±3.33 pg/ml respectively (P<0.05); The expression of NF-кB protein (OD value 0.36±0.04) in CIH group was increased when compared to the control (OD value 0.23±0.03) (P<0.05). The HIF-1αand MMP-9 mRNA expression in CIH group were also higher than that in the control, 2.36E-2±8.62E-3 vs 1.03E-2±3.00E-3 and 8.97E-1±2.90E-2 vs 6.75E-1±1.03E-2 respectively (P<0.05); there were inflammation reaction in CIH rats lung tissue.[CONCLUSION] The concentration of 8-iso-PGF₂α,MDA, IL-6, TNF-α, VEGF and ET-1 in plasma in CIH rats were significantly increased; the expression of NF-кB protein and HIF-1α, MMP-9 at mRNA were also markedly elevated; there are inflammation reaction, oxidative stress and endothelial dysfunction in rats with CIH. Partâ…¡To investigate the effects of N-acetylcysteine intervent on inflammation reaction, oxidative stress and endothelial cell dysfunction in rats with chronic intermittent hypoxia.[OBJECTIVE] To investigate the effects of N-acetylcysteine intervent on inflammation reaction, oxidative stress and endothelial dysfunction in rats with chronic intermittent hypoxia.[METHODS] To establish a chronic imtermittent hypoxia(CIH) animal model in rats , in order to mimic the intermittent hypoxia of obstructive sleep apnea-hypopnea syndrome (OSAHS) in humans. 24 healthy male SD rats were randomly assigned to two equal groups: the CIH+ physiological saline control group and the CIH+N-acetylcysteine (NAC) group. The rats in two groups were placed in an animal chamber subjected to chronic imtermittent hypoxia (nadir ambient oxygen concentration 6-7 %, maximum ambient oxygen concentration 20-21%, Continuing respectively to 5-7 second) for 8 hours per day (from 9AM to 5PM) and the experimental lasted for 35 days. The rats in CIH+NAC group were gived the peritoneal injection with N-acetylcysteine, the rats in CIH+ CIH+ physiological saline control group were gived the peritoneal injection with physiological saline half an houre before they were placed in animal chamber with chronic imtermittent hypoxia. After the experiment, We measured the level of 8-iso-PGF₂α, MDA, IL-6, TNF-α, VEGF and ET-1 in plasma by ELISA. Western blot were performed to study the expression of NF-кB in rat lung specimens. HIF-1αand MMP-9 mRNAexpressions and microscopic examination were detected in lung tissues..[RESULTS] The weight of rats in CIH+NAC group were overweight the rats in CIH+ physiological saline control group , 411.24±17.32g vs 352.85±39.08g respectively (P<0.05); the concentration of 8-iso-PGF₂α, MDA, IL-6, TNF-α, VEGF and ET-1 in plasma in CIH+NAC group were lower than that in CIH+ physiological saline control group, 179.61±13.85 vs 394.96±33.11 pg/ml (P<0.05), 8.22±3.90 vs 18.25±4.43 pg/ml (P<0.05), 26.26±6.68 vs 110.10±13.52 pg/ml(P<0.05), 26.99±9.69 vs 119.31±38.29 pg/ml (P<0.05), 49.32±3.84 vs 108.18±22.08 pg/ml and 12.06±2.20 vs 18.43±3.24 pg/ml respectively (P<0.05); The expression of NF-кB protein (OD value 0.24±0.03) in CIH+NAC group was decreased when compared to the CIH+ physiological saline control (OD value 0.37±0.02) (P<0.05). The HIF-1αand MMP-9 mRNA expression in CIH+NAC group were also reduced when compared to the CIH+ physiological saline control, 5.10E-3±4.19E-4 vs 3.28E-2±4.51E-4,5.38E-1±6.06E-2 vs 8.29E-1±7.38E-2 respectively(P<0.05); the inflammation reaction in NAC rats lung tissue was relieved.[CONCLUSION] The concentration of 8-iso-PGF₂α, MDA, IL-6, TNF-α, VEGF and ET-1 in plasma in CIH+NAC group were significantly decreased; the expression of NF-кB protein and HIF-1α, MMP-9 at mRNA were also markedly reduced; NAC can palliate the inflammation reaction, oxidative stress and endothelial dysfunction in rats with CIH.