| Objectives To investigate the effect of grape seed proanthocyanidin on inflammation andlearning memory capacity and phosphorylated p38MAPK and IL-1β in a rat model ofobstructive sleep apnea hypoxia syndrome (OSAHS).Methods A total of80healthy male SD rats were randomly allocated into four groups: thecontrol group (n=20), the model group (n=20), the low dose of grape seed proanthocyanidinintervention group (n=20), and the high dose of grape seed proanthocyanidin interventiongroup (n=20) using digital random method. Rats in the control group was exposed to the air;those in the other3groups suffered from intermittent hypoxia conditions for6weeks.2weeks before the hypoxia treatment, rats in low and high dose of grape seedproanthocyanidin groups were began to intragastricly administrate grape seedproanthocyanidin at dose of100and200mg/kg, once per day, respectively. At the2nd and6th week of hypoxia treatment, the learning memory capacity of rats were assessed by theMorris water maze, neuron pathology in hippocampal region was observed using electronmicroscope, the Malondialdehyde (MDA) contents and superoxide dismutase (SOD)activity were detected with colorimetry, and the expressions of phosphorylated p38MAPKand IL-1proteins were detected by Western blot.Results1Compared with the control group, the model group showed prolonged escapinglatency and decreased frequency of crossing the platform at the2nd and6th week ofhypoxia treatment (P<0.05). Compared with the model group, the intervention groupshowed shortened escaping latency and increased frequency of crossing the platform at the2nd and6th week of hypoxia treatment (P<0.05). Compared with the low dose group, thehigh dose group showed shortened escaping latency and increased frequency of crossing theplatform at the2nd and6th week of hypoxia treatment (P<0.05).2On electron microscopy,the control group showed regular hippocampus neuron cell nucleus, clear nucleoli andnuclear membrane, distinct edge, normal structure of organelles within neurons, andcomplete synaptic structure. The model group showed hippocampus nerve cell edema, loosenucleus with normal structure, mitochondria edema, and vague synaptic vesicles withdecreased number at the2nd week of hypoxia treatment; and hippocampus neuron cellnucleolus disappearance or chromatin margination, the decreased mitochondria, unidentifiedsynaptic vesicles at the6th week of hypoxia treatment. The intervention group showed relieved damage in ultrastructure of nerve cells, especially in the high dose group. On lightmicroscope, the control group showed normal hippocampus nerve cell structure. The modelgroup showed hippocampus nerve cell edema, misaligned cells, loose structure, light dyeing,and a small amount of degeneration necrosis nerve cells at the2nd week of hypoxiatreatment; and relatively more degeneration and necrosis of neurons at the6th week ofhypoxia treatment. The intervention group showed relieved damage in morphologicalstructure of nerve cells and the decrease in the number of nerve cell death. There was astatistically difference in the number of survived hippocampus nerve cell between thecontrol group and the model group at the2nd and6th week of hypoxia treatment (P<0.05).There was a statistically difference in the number of survived hippocampus nerve cellbetween the intervention group and the control group (P<0.05). The number of survivedhippocampus nerve cell was higher in the high dose group than the low dose group(P<0.05).3The model group showed higher MDA content and lower SOD levels comparedwith the control group at the2nd and6th week of hypoxia treatment (P<0.05). Theintervention group showed lower MDA content and higher SOD levels compared with themodel group at the2nd and6th week of hypoxia treatment (P<0.05). The high dose groupshowed lower MDA content and higher SOD levels compared with the low dose group atthe2nd and6th week of hypoxia treatment (P<0.05).4There was a statistically differencein phosphorylated p38MAPK immune reaction between the control group and the modelgroup at the2nd and6th week of hypoxia treatment (P<0.05). The intervention groupshowed lower phosphorylated p38MAPK immune reaction at the2nd and6th week ofhypoxia treatment than the model group (P<0.05). The high dose group showed lowerphosphorylated p38MAPK immune reaction compared with the low dose group (P<0.05).There was a statistically difference in LI-1β immune reaction between the control group andthe model group at the2nd and6th week of hypoxia treatment (P<0.05). The interventiongroup showed lower LI-1β immune reaction at the2nd and6th week of hypoxia treatment(P<0.05). The high dose group showed lower LI-1β immune reaction compared with thelow dose group at the2nd and6th week of hypoxia treatment (P<0.05). There was astatistically difference in phosphorylated p38MAPK protein levels between the controlgroup and the model group at the2nd and6th week of hypoxia treatment (P<0.05). Theintervention group showed lower phosphorylated p38MAPK protein levels at the2nd and6th week of hypoxia treatment than the model group (P<0.05). The high dose group showedlower phosphorylated p38MAPK protein levels compared with the low dose group at the 2nd and6th week of hypoxia treatment (P<0.05). There was a statistically difference in LI-1β protein levels between the control group and the model group at the2nd and6th week ofhypoxia treatment (P<0.05). The intervention group showed lower LI-1β protein levels atthe2nd and6th week of hypoxia treatment than the model group (P<0.05). The high dosegroup showed lower LI-1β protein levels compared with the low dose group at the2nd and6th week of hypoxia treatment (P<0.05).Conclusions The application of grape seed proanthocyanidin could reduce oxidative stress,relieve the damage of ultrastructure, and promote the recovery of learning memory capacityin a rat model of OSAHS. The grape seed proanthocyanidin could inhibit thephosphorylated p38MAPK and LI-1β in hippocampal region in a rat model of OSAHS. |
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