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Objective To investigate the changes in the expression of phosphatidylinositol 3?kinase(PI3?K),mammalian target of rapamycin (mTOR)and Beclin?1 in the hippocampus of normal rats and intermittent hypoxia rats with cerebral ischemia/reperfusion ,so as to explore the role of PI3K/mTOR/autophagy pathway in global cerebral ischemia/reperfusion injury aggravated by intermittent hypoxia. Methods A total of 80 healthy male Wistar rats were randomly divided into sham operation group(SO group,n=20),merely ischemia/reperfusion group(I/R group,n=20),intermittent hypoxia for 7?day ischemia/reperfusion group(IH7+I/R group,n=20),and intermittent hypoxia for 21?day ischemia/reperfusion group(IH21+I/R group,n=20). IH7+I/R group and IH21+I/R group were respectively given intermittent hypoxia for 7 days and 21 days before ischemia/reperfusion. The cerebral ischemia/reperfusion model was established by modified Pulsinelli four?vessel occlusion method. The morpholog?ical changes of nerve cells in hippocampal CA1 region were observed by HE staining and electron microscope. The protein expressions of PI3?K, mTOR and Beclin?1 of nerve cells in hippocampal CA1 region were detected by immunohistochemical staining and RT?PCR. The learning memory capacity of rats were assessed by the Morris water maze test. Results Compared with SO group,I/R group increased the never cells morphology damages,reduced the number of survival neurons,and declined the ability of learning and memory(P<0.05). Immunohistochemistry showed that the number of PI3?K immunoreactive cell,mTOR immunoreactive cell and Beclin?1 immunoreactive cell increased in I/R group compared with S0 group(P<0.05). RT?PCR showed that the expressions of PI3?K,mTOR and Beclin?1 increased in I/R group compared with S0 group(P<0.05). Compared with I/R group,intermittent hypoxia groups increased the never cells morphology damages,decreased the number of survival neu?rons,and declined the ability of learning and memory(P<0.05). Immunohistochemistry showed that the number of PI3?K immunoreactive cell, mTOR immunoreactive cell and Beclin?1 immunoreactive cell increased in IH7+I/R and IH21+I/R groups compared with I/R group(P<0.05). RT?PCR showed that the expressions of PI3?K,mTOR and Beclin?1 increased in IH7+I/R and IH21+I/R groups compared with I/R group(P<0.05),and the changes were more significant in IH21+I/R group(P<0.05). Conclusion Intermittent hypoxia can aggravate neurological injury after ischemia,which is related to PI3K/mTOR/autophagy pathway activation.
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@#Objective To investigate the effect of grape seed proanthocyanidin extract (GSPE) on ultrastructure injury in hippocampous and cognition impairment in rat model of obstructive sleep apnea hypoxia. Methods 80 male Sprague-Dawley rats were randomly divided into control group, model group, high and low dose GSPE groups. The control group was exposed in air, while the model group was suffered from intermittent hypoxia conditions (50 ml/L, 8 h everyday, for 2 or 6 weeks), and the GSPE groups accepted GSPE 200 mg/kg or 100 mg/kg 2 weeks respectively before hypoxia. Pathology in hippocampal region was observed under electromicroscope. Malondialdehyde (MDA) contents and superoxide dismutase (SOD) activity were detected with colorimetry, and apoptotic cells were measured with TUNEL. The cognition function of rats was assessed with the Morris water maze (MWM). Results The ultrastructure in hippocampous was significantly injured,with the increase of MDA and decrease of SOD (P<0.001) in the model group. The apoptotic cells increased (P<0.001). The escaping latency prolonged (P<0.001) and the frequency of crossing the platform decreased (P<0.001) in MWM test in the model group. Compared with the model group, the GSPE groups decreased in MDA content, increased in SOD level, decreased in apoptotic cells and ultrastructure damages, shortened the escaping latency, and increased the frequency of crossing the platform (P<0.001), especially in the high dose group (P<0.05). Conclusion GSPE can relieve the damage of ultrastructure and improve cognition function after obstructive sleep apnea hypoxia in rats.
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Objective To investigate the effects of grape seed proanthocyanidin(GSPE) on mitochondrial injury in hippocampus and learning-memory impairment after obstructive sleep apnea hypoxia in rats.Methods Male SD rats(n=80) were randomly divided into control group,model group,low dose of GSPE treatment group and high dose of GSPE treatment group.Rats in control group were exposed in air,the model group were suffered from intermittent hypoxia conditions (50 ml/L,8-hour-intermittent hypoxia everyday,and the duration of experiment 2 and 6 weeks,respectively).Mitochondrion pathology in hippocampal region was observed using electron microscope;malondialdehyde (MDA) contents and superoxide dismutase activity were detected by colorimetry and apoptotic cells was measured by TUNEL method.The cognitive function of rats in each group was assessed with the Morris water maze (MWM).Results After hypoxia,mitochondrion was significantly injured.The MDA contents were increased(79.86 ± 2.52,88.26 ± 2.86) and SOD level decreased (70.67 ± 6.70,64.26 ± 7.86).The number of neural apoptotic cells was significantly enhanced (9.68 ± 0.79,15.9 ± 2.92).MWM test showed that the escaping latency was prolonged and the frequency of crossing the platform was decreased (P ＜ 0.05).Compared with that in the model group,low dose of GSPE decreased MDA contents (76.38 ± 1.96,82.16 ±2.02),increased SOD level(76.20 ± 6.86,70.58 ± 6.86),and decreased apoptotic cells (6.60 ± 0.69,9.54 ±1.36).MWM test showed that the escaping latency was shortened and the frequency of crossing the platform was increased in GSPE treatment groups(P ＜ 0.05).Compared with low dose of GSPE,high dose of GSPE decreased MDA contents increased SOD level and decreased apoptotic cells.MWM test showed that the escaping latency was shortened and the frequency of crossing the platform was increased (P＜ 0.05).Conclusion GSPE can attenuate mitochondrial injury and improve learning-memory function after obstructive sleep apnea hypoxia.
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Objective To clarify the effects of exercise- and food intake restriction-induced weight reduction on expression of ghrelin in plasma and stomach of obese rats,and to explore the role of ghrelin during weight loss. Methods 100 weaned Sprague-Dawley(SD) rats were randomly divided into control group(fed with standard chow,n= 20) and model group (two-bottle-feeding method,fed with standard chow and high-fat diet simultaneously, n=80). After 20 weeks feeding, Lee' s index of control was used as the reference of diet-induced obesity identification, and then diet-induced obese rats were randomly divided into four groups:obese control group,swimming group,food intake restriction group and swimming+food intake restriction group, eight rats in each group. Rats in swimming group underwent long-term(40 min,6 days/week for 5 weeks)swimming exercise. Calorie in food intake restriction group was restricted 1/3 of normal kcal for 3 weeks,and subsequently restricted 1/3 for 2 weeks. Swimming+food restriction group had the same intervention as swimming and food restriction group. 8 normal diet rats were also chosen as controls. After five weeks of treatments,peripheral fat mass of testis and kidney,ghrelin proteins in plasma and stomach,and ghrelin mRNA in stomach were measured. Results Gastric ghrelin protein and mRNA were significantly lower in obese control group than those in normal control group (P0.05). Compared with obese control group,weight and fat mass in all weight loss groups declined notablely(P<0.05);in swimming and swimming+food restriction groups,the expression of ghrelin protein or mRNA in plasma or stomach increased remarkably( P<0.05); in food restriction group, the level of ghrelin mRNA raised significantly (P<0.05), while ghrelin protein in plasma and stomach had not change. Conclusion The level of ghrelin increased in exercise induced weight loss,while showed no significant change in food intake restriction group, suggested that ghrelin might be involved in the process of weight loss induced by exercise.