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Objective:To evaluate the relationship between early postoperative cognitive dysfunction and neuromodulator protein 1β(NRG1β) in aged rats.Methods:Pathogen-free healthy male Sprague-Dawley rats, aged 18-20 months, weighing 600-700 g, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), operation group (group O) and NRG1β group (group N). Exploratory laparotomy was performed in group O and group N. NRG1β 0.5 μg/kg was slowly injected into the lateral ventricle on 1 day before surgery in group N, while the equal volume of 0.1 mol/L phosphate buffer solution was given instead in C and O groups.Learning and memory function was assessed using Morris water maze test performed at day 3 after operation.The rats were then sacrificed, and the hippocampi were removed for determination of the expression of nuclear factor kappa B (NF-κB) p65 (by Western blot) and contents of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay). Results:Compared with group C, the postoperative escape latency was significantly prolonged, the expression of NF-κB p65 was up-regulated, and the contents of IL-1β and TNF-α were increased in group O and group N ( P<0.05). Compared with group O, the postoperative escape latency was significantly shortened, the expression of NF-κB p65 was down-regulated, and the contents of IL-1β and TNF-α were decreased in group N ( P<0.05). Conclusion:NRG1β is involved in the endogenous protective mechanism of early postoperative cognitive dysfunction probably by inhibiting the activation of NF-κB pathway and inhibiting inflammatory responses in aged rats.
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Objective To evaluate the role of Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 2 (ROCK2) signaling pathway in propofol-induced neuroapoptosis in the hippocampus of newborn rats.Methods Experiment Ⅰ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1×106 cells/ml and divided into 2 groups (n=6 each) using a random number table:solvent control group (C group) and propofol group (P group).Propofol was added with the final concentration of 60 μg/ml in group P.Dimethyl sulfoxide was added with the final concentration of 0.04％ in group C.The expression of RhoA and ROCK2 in hippocampal neurons was measured by Western blot at 24 h of incubation.Experiment Ⅱ Primarily cultured hippocampal neurons were seeded in 6-well culture plates at a density of 1 × 106 cells/ml and divided into 3 groups (n =6 each) using a random number table:solvent control group (C group),propofol group (P group) and propofol plus specific RhoA/ROCK2 signaling pathway blocker Y27632 group (P+Y group).Propofol was added with the final concentration of 60 μg/ml in group P.Propofol at the final concentration of 60 μg/ml and Y27632 at the final concentration of 10 μmol/L were added in group P+Y.Dimethyl sulfoxide was added with the final concentrauon of 0.04％ in group C.At 24 h of incubation,the neuroapoptosis in hippocampi was detected by flow cytometry,and the expression of activated caspase-3 in hippocampal neurons was measured by Western blot.The apoptotic rate was calculated.Results Experiment Ⅰ Compared with group C,the expression of RhoA and ROCK2 in hippocampal neurons was significantly up-regulated in group P (P＜0.05).Experiment Ⅱ Compared with group C,the apoptotic rate of hippocampal neurons was significantly increased,and the expression of activated caspase-3 was up-regulated in P and P+Y groups (P＜0.05 or 0.01).Compared with group P,the apoptotic rate of hippocampal neurons was significantly decreased,and the expression of activated caspase-3 was down-rcgulatcd in group P + Y (P＜ 0.05).Conclusion Activation of RhoA/ROCK2 signaling pathway is involved in propofol-induced neuroapoptosis in hippocampi of newborn rats.
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Objective To evaluate the role of conventional protein kinase Cγ (cPKCγ)/growthassociated protein-43 (GAP-43) signaling pathway in ketamine-induced apoptosis in hippocampal neurons of developing rats in an in vitro experiment.Methods Primarily cultured hippocampal neurons were seeded in culture plates at a density of 1×10.6 cells/ml and divided into 2 groups (n=10 each) using a random number table:control group (C group) and ketamine group (K group).Group C received no treatment.Ketamine was added with the final concentration of 300 μmol/L in group K.At 12 h of culture or incubation,the apoptosis in hippocampal neurons was detected by flow cytometry.The apoptotic rate was calculated.The expression of cPKCγ,GAP-43 and phosphorylated GAP-43 in hippocampal neurons was measured by Western blot.Results Compared with group C,the apoptotic rates of hippocampal neurons were significantly increased,and the expression of cPKCγ,GAP-43 and phosphorylated GAP-43 was down-regulated in group K (P<0.01).Conclusion The mechanism by which ketamine induces apoptosis in hippocampal neurons of developing rats may be related to inhibition of cPKCγ/GAP-43 signaling pathway activation in an in vitro experiment.
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Objective To investigate the effects of sevoflurane postconditioning on cardiomyocyte apoptosis during myocardial ischemia-repeffusion (I/R) in rats.Methods Forty-five healthy male Wistar rats weighing 250-280 g were randomly divided into 3 groups ( n =15 each):group sham operation ( group S) ; group I/R and group sevoflurane postconditioning (group Spo).The animals were anesthetized with intraperitoneal 3％ pentobarbital 45 mg/kg,tracheally intubated and mechanically ventilated.Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion in groups I/R and Spo.In group Spo the animals inhaled 2.5％ sevoflurane for 5 min starting from 1 min before reperfusion was started.The animals were sacrificed at the end of 120 min reperfusion.Their hearts were removed for measurement of infarct size and the area at risk and determination of apoptotic index (the number of apoptotic cells/the total number of cells) and Bcl-2 and Bax protein and mRNA expression.Results Sevoflurane postconditioning significantly reduced infarct size in group Spo as compared with group I/R.There was no significant difference in area at risk between groups I/R and Spo.Myocardial I/R significantly increased the apoptotic index,Bcl-2 and Bax protein and mRNA expression in group I/R as compared with group S.Sevoflurane postconditioning significantly decreased apoptotic index and Bax protein and mRNA expression but increased Bcl-2 protein and mRNA expression in group Spo as compared with group I/R.Conclusion Sevoflurane postconditioning attenuates myocardial I/R injury by redncing myocardial apoptosis,up-regulating Bcl-2 expression and down-regulating Bax expression.
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Objective To investigate the effect of sevoflurane preconditioning-postconditioning on thromboxane A2 and prostaglandin I2 during myocardial ischemia-reperfusion (I/R) in rats. Methods Fifty healthy male Wistar rats weighing 250-280 g were randomly divided into 5 groups (n = 10 each) : sham operation group (group S) , I/R group, sevoflurane preconditioning group (group Spr), sevoflurane postconditioning group (group Spo)and combination of sevoflurane preconditioning and postconditioning group (group Spr + po). Myocardial I/R was produced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 2 h reperfusion in anesthetized rats. In group S the anterior descending branch was only exposed but not ligated. Group Spr received 15 min inhalation of 2.5 % sevoflurane and 15 min wash-out 30 min before ischemia. Group Spo received 5 min inhalation of 2.5% sevoflurane 1 min before reperfusion. Arterial blood samples were taken at 2 h of reperfusion for determination of the levels of MB isoenzyme of creatine kinase (CK-MB) , lactate dehydrogenase (LDH) , cardiac troponin I (cTnI), thromboxane B2(TXB2), and 6-keto-prostaglandin (6-keto-PGF1α) and platelet maximum aggregation rate. TXB2/6-keto-PGF1α ratio was calculated. The myocardial tissues were taken for microscopic examination. Mitochondria] injury was assessed by using Flameng score and stereology (Specific surface, δ and Numerical density on area, NA) .Results Compared with group S, the levels of CK-MB, LDH, cTnI, TXE2 and 6-ketoPGF1α, TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly increased, while δ and NA were significantly decreased in group I/R (P < 0.05 or 0.01) . The levels of CK-MB,LDH and cTnI, TXB2/6-keto-PGF1α ratio and Flameng score were significantly lower, and 6-keto-PGF1α level, δand NA were significantly higher in Spr and Spo groups than in group I/R ( P < 0.05 or 0.01) . The levels of CKMB, LDH, cTnI and TXB2 , TXB2/6-keto-PGF1α ratio, platelet maximum aggregation rate and Flameng score were significantly lower and 6-keto-PGF1α level,δ and NA were significantly higher in group Spr + po than in Spr and Spo groups(P < 0.05). Conclusion Sevoflurane preconditioning-postconditioning can reduce myocardial I/R injury through inhibiting the release of thromboxane A2 and promoting the release of prostaglandin I2 in rats.
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Objective To investigate the effect of sevoflurane postconditioning on the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase during myocardial ischemia-reperfusion (I/R) in rats and the possible mechanism. Methods Forty-five healthy male Wistar rats weighing 250-280 g were randomly divided into 3 groups ( n = 15 each): sham operation group (group S), I/R group and sevoflurane postconditioning group (group Spo). Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion. In group S the anterior descending branch was only exposed but not ligated. Group Spo received 5 min inhlation of 2.5% sevoflurane 1 min before reperfusion. The myocardial tissues were taken at 2 h of reperfusion for determination of infarct size and activities of Na+ -K+ -ATPase and Ca2 * -Mg2 * -ATPase. Results The infarct size was significantly larger and the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were signifi cantly lower in group I/R than in group S ( P ＜ 0.05). The infarct size was significantly smaller and the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase were significantly higher in group Spo than in group I/R (P ＜ 0.05 ). Conclusion Sevoflurane postconditioning can reduce myocardial I/R injury through increasing the activities of Na+ -K+ -ATPase and Ca2+ -Mg2+ -ATPase.