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Objective:To evaluate the effect of sleep fragmentation on postoperative cognitive dysfunction (POCD) and hippocampal glutaminergic metabolism in aged mice anesthetized with isoflurane.Methods:Forty healthy SPF-grade male C57BL/6J mice, aged 18 months, weighing 20-30 g, were divided into 4 groups ( n= 10 each) by the random number table method: normal control group (group C), sleep fragmentation group (group SF), isoflurane anesthesia/surgery group (group I/S), and sleep fragmentation plus isoflurane anesthesia/surgery group (group SF+ I/S). Group C did not received any treatment. Group SF received sleep fragmentation for 24 h. The right carotid artery exposure was performed under isoflurane anesthesia in group I/S. Group SF+ I/S received isoflurane anesthesia/right carotid artery exposure at 24 h after sleep fragmentation. The metabolic levels of glutamate (Glu), glutamine (Gln), Glu/Gln complex (Glx), and N-acetylaspartate (NAA) and their ratio to creatine (Cr) were measured by in vivo 9.4T hydrogen proton magnetic resonance spectroscopy at 2 h after anaesthesia. Y maze and Morris water maze tests were used to evaluate the cognitive function at 1-7 days after surgery. The mice were sacrificed after the behavioral testing, brain tissues were immediately obtained, and the number of Nissl bodies and density of dendritic spines in the hippocampal CA1 region were measured by Nissl staining and Golgi staining, respectively. Results:Compared with group C, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr, Gln/Cr and Glx/Cr in the hippocampal CA1 region were increased, and the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in SF, I/S and SF+ I/S groups ( P<0.05). Compared with group SF and group I/S, the percentage of exploration time and shuttle times at the novel arm were significantly decreased, the number of crossing the original platform was decreased, the time of stay at the target quadrant was shortened, the ratios of Glu/Cr and Glx/Cr in hippocampal CA1 region was increased, the ratio of NAA/Cr was decreased, and the number of Nissl bodies and density of dendritic spines were decreased in group SF+ I/S ( P<0.05). Conclusions:Sleep fragmentation exacerbates POCD in aged mice anesthetized with isoflurane, and the mechanism is related to nerve injury induced by abnormality in hippocampal glutaminergic metabolism excitability.
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Background Benzo[a]pyrene (BaP) is neurotoxic and can cause neuronal damage by oxidative stress. Proanthocyanidin (PC) has antioxidant activity, and its mechanism may related to nuclear factor-erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway. Objective To explore potential protective effect of PC on hippocampal neuron injury induced by BaP oxidative stress. Methods Hippocampal neurons of neonatal SD rats delivered within 24 h were isolated and cultured, and cell activity was detected by cell counting kit-8 (CCK-8) method. According to the pre-experimental results, a control group and three BaP groups of 10, 20 and 40 µmol·L−1 were set up for Stage I experiment. The length of neurites and number of branches of hippocampal neurons in each group were observed by immunofluorescence method. Reactive oxygen species (ROS) fluorescence probe method was used to measure ROS levels in cells. Real-time quantitative fluorescent polymerase chain reaction (qRT-PCR) and Western blotting were used to detect the mRNA and protein expression of Nrf2, Kelch-like epichlorohydrin associated protein-1 (Keap1), HO-1, B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X (Bax) in hippocampal neurons of each group, respectively. According to the results of Stage I experiment, three group were set up, including control group, BaP alone treatment group (BaP 20 µmol·L−1), and PC intervention group (BaP 20 µmol·L−1 + PC 2.5 µg·mL−1) for Stage II experiment, with the same protocol as Stage I. Results For Stage I experiment, compared with the control group, the 10, 20, and 40 µmol·L−1 BaP groups showed gradually shortened length of neurites [(177.60±3.49), (142.40±6.52), and (100.50±19.40) µm] (P<0.05) and decreased number of branches (8.00±1.00, 6.33±1.53, 4.33± 0.58) of hippocampal neurons (P<0.05); increased ROS production (2.38±0.33, 8.08±0.26, 9.86±0.19) (P<0.05); the qRT-PCR results showed that the mRNA expression levels of Nrf2 (0.35±0.03, 0.25±0.01, 0.13±0.03), Keap1 (0.70±0.01, 0.47±0.03, 0.15±0.02), HO-1 (0.77±0.02, 0.60±0.02, 0.32±0.01), and Bcl-2 (0.65±0.03, 0.47±0.02, 0.18±0.02) gradually decreased, and the mRNA expression level of Bax gradually increased (1.24±0.01, 2.25±0.15, 4.98±0.30) (P<0.05); the Western blotting results showed that the protein expression trends of Nrf2, Keap1, HO-1, Bcl-2, and Bax were consistent with the mRNA results. For Stage II experiment, compared with the BaP alone treatment group, the length of neurites in the PC intervention group became longer, (149.90±3.01) μm vs (202.00±4.45) μm (P<0.05), the number of branches increased, (4.67±0.58) vs (8.33±0.58) (P<0.05); the ROS production reduced, (10.81±0.63) vs (7.31±0.70) (P<0.05); the mRNA expression levels of Nrf2, Keap1, HO-1, and Bcl-2 increased (P<0.05), and the mRNA expression levels of Bax decreased (P<0.05); the Nrf2, Keap1, HO-1, and Bcl-2 protein expression levels increased (P<0.05), and Bax protein expression level decreased (P<0.05). Conclusion PC may exert neuroprotective effects by activating the Nrf2-HO-1 signaling pathway, inhibiting BaP-induced oxidative stress in neuronal cells, and reducing cytotoxicity.
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Objective Observed the characteristics and influence factors of blood pressure circadian rhythm in continuous ambulatory peritoneal dialysis patients.To investigate the effect of residual renal function and cardiac function.Methods Prospectively collected 120 cases of continuous ambulatory peritoneal dialysis from June 2016 to March 2017 in Tangshan renal medicine dialysis centers,who combined with hypertension were treated with peritoneal dialysis for more than 3 months.According to the dynamic monitoring blood pressure circadian rhythm of blood pressure,120 cases were divided into the normal rhythm of blood pressure and the abnormal blood pressure rhythm group.Collected medical history;Tested related test index respectively;Cardiac ultrasound.According to the formula to calculate residual renal function,left ventricular mass index,Eingabe/Ausgabe,Ejection Fraction.Univariate and multivariate unconditional logistic regression analysis was used to analyze the risk factors of circadian rhythm of blood pressure.Stepwise multiple linear regression analysis was used to analyze the risk factors of residual renal function and cardiac function.Results CAPD patients with normal blood pressure rhythm in 14 cases(11.7％),abnormal blood pressure rhythm in 106 cases(88.3％),Among them,non dipper blood pressure accounted for 75 cases(62.5％).Single factor and multiple factors unconditioned logistic regression analysis revealed that after the comparison of gender and age,Risk factors for abnormal circadian rhythm of blood pressure were:UA(OR=1.197,95％CI:1.099-1.441),CRP(OR=1.170,95％CI:1.061-1.331),RRF(OR=1.389,95％CI:1.160-1.779).Using stepwise multiple linear regression analysis of dangerous factors affecting residual renal function and cardiac function,we found:Residual renal function negatively correlated with left ventricular myocardial mass index,systolic blood pressure drops at night rate,and ultrafiltration volume;LVMI (cardiac function) Positively correlated with 24 h average systolic blood pressure,and negatively correlated with systolic blood pressure drop ratio and residual renal function at night.Abnormal circadian rhythm of blood pressure may lead to the decline of residual renal function and cardiac function.Conclusions UA,CRP and RRF may affect the CAPD patients blood pressure circadian rhythm.At the same time,abnormal circadian rhythm of blood pressure may lead to the decline of residual renal function and cardiac function.Therefore,pay attention to the monitoring and control of ABPM,can better protect the residual renal function and improve cardiac function,so as to prolong and improve the survival time and quality of life of patients with CAPD.