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Objective@#To evaluate the effect of exogenous insulin on endoplasmic reticulum stress in myocardial tissues during insulin resistance in the rabbits undergoing cardiopulmonary bypass (CPB).@*Methods@#Forty healthy adult New Zealand white rabbits of both sexes, weighing 2.5-3.0 kg, were divided into 4 groups (n=10 each) using a random number table method: control group (group C), CPB group, CPB plus insulin group (group I) and CPB plus normal saline group (group NS). Group C received no treatment.An insulin resistance model was established in group CPB.Insulin was continuously infused (the infusion rate was adjusted according to the blood glucose) starting from establishing CPB to 1 day after operation in group I. The equal volume of normal saline was given starting from establishing CPB to 1 day after operation in group NS.Blood samples were collected from the left femoral artery, and myocardial tissues obtained before CPB (T1) and at 15, 30 and 60 min after aortic opening (T2-4). The level of blood glucose was determined using oxidase method, the level of glucagon was detected by the radioimmunoassay method, and the insulin resistance index was calculated.The expression of inositol-requiring protein-1α(IRE1α), XBP1 and caspase-12 was measured by Western blot.The expression of IRE1α, XBP1 and caspase-12 mRNA was measured by fluorescent quantitative real-time polymerase chain reaction.Cell apoptosis was detected by TUNEL.@*Results@#Compared with group C, blood glucose and glucagon levels at T2-4 and insulin resistance index at T4 were significantly increased, and the expression of inositol-requiring protein-1α(IRE1α), XBP1 and caspase-12 protein and mRNA was up-regulated at T4 in CPB, I and NS groups (P<0.05). Compared with group CPB, blood glucose and glucagon levels at T2-4 and insulin resistance index at T4 were significantly decreased, and the expression of IRE1α, XBP1 and caspase-12 protein and mRNA was down-regulated at T4 in group I (P<0.05).@*Conclusion@#Exogenous insulin significantly improves insulin resistance in myocardial tissues, and the mechanism is related to inhibiting endoplasmic reticulum stress and reducing cell apoptosis in the rabbits undergoing CPB.
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Objective To evaluate the effect of exogenous insulin on inositol-requiring protein 1α (IRE1α)-X-box-binding protein 1 (XBP1) signaling pathways in pancreatic tissues during cardiopulmonary bypass (CPB)-caused insulin resistance in rabbits.Methods Forty healthy adult New Zealand white rabbits of both sexes,weighing 2.5-3.0 kg,were divided into 4 groups (n =10 each) using a random number table method:control group (group C),group CPB,insulin group (group I),and normal saline control group (group NS).CPB was established in group CPB.Insulin was intravenously infused in a dose of 1.2 ml/h from establishing CPB to 1 day after operation,and the infusion rate of insulin was regulated according to the blood glucose (maintaining at 7.2-8.3 mmol/L) in group I.CPB was established,and normal saline was intravenously infused from the beginning of operation to 1 day after operation in group NS.Before CPB (T1) and at 15,30 and 60 min after aortic opening (T2-4),blood samples were collected from the left femoral artery,the plasma was separated,the blood glucose level was detected by oxidase method,the level of glucagon was detected by the radioimmunoassay method,and the insulin resistance index was calculated.Animals were sacrificed at T4,and pancreatic tissues were obtained for determination of the expression of IRE1α,XBP1,c-Jun N-terminal kinase (JNK) and caspase-12 protein and mRNA (by Western blot or fluorescent quantitative real-time polymerase chain reaction) and for examination of the pathological changes (by haematoxylin and eosin staining).Results Compared with group C,blood glucose and glucagon concentrations and insulin resistance index were significantly increased at T2-4,and the expression of IRE1α,XBP1,JNK and caspase-12 was up-regulated at T4 in CPB,I and NS groups (P＜0.05).Compared with group CPB or group NS,blood glucose and glucagon concentrations and insulin resistance index were significantly decreased at T2-4,the expression of IRE1α,XBP1,JNK and caspase-12 was down-regulated at T4 (P＜0.05),and the pathological changes of pancreatic tissues were significantly attenuated in group I.There was no significant difference in the parameters mentioned above between group CPB and group NS (P＞0.05).Conclusion The mechanism by which exogenous insulin reduces CPB-caused insulin resistance may be related to inhibiting IRE1α-XBP1 signaling pathways in pancreatic tissues of rabbits.
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Objective To evaluate the effect of exogenous insulin on endoplasmic reticulum stress in myocardial tissues during insulin resistance in the rabbits undergoing cardiopulmonary bypass (CPB).Methods Forty healthy adult New Zealand white rabbits of both sexes,weighing 2.5-3.0 kg,were divided into 4 groups (n =10 each) using a random number table method:control group (group C),CPB group,CPB plus insulin group (group Ⅰ) and CPB plus normal saline group (group NS).Group C received no treatment.An insulin resistance model was established in group CPB.Insulin was continuously infused (the infusion rate was adjusted according to the blood glucose) starting from establishing CPB to 1 day after operation in group Ⅰ.The equal volume of normal saline was given starting from establishing CPB to 1 day after operation in group NS.Blood samples were collected from the left femoral artery,and myocardial tissues obtained before CPB (T1) and at 15,30 and 60 min after aortic opening (T2-4).The level of blood glucose was determined using oxidase method,the level of glucagon was detected by the radioimmunoassay method,and the insulin resistance index was calculated.The expression of inositol-requiring protein-1α(IRE1α),XBP1 and caspase-12 was measured by Western blot.The expression of IRE1α,XBP1 and caspase-12 mRNA was measured by fluorescent quantitative real-time polymerase chain reaction.Cell apoptosis was detected by TUNEL.Results Compared with group C,blood glucose and glucagon levels at T2-4 and insulin resistance index at T4 were significantly increased,and the expression of inositol-requiring protein-1α (IRE1α),XBP1 and caspase-12 protein and mRNA was up-regulated at T4 in CPB,I and NS groups (P＜0.05).Compared with group CPB,blood glucose and glucagon levels at T2-4 and insulin resistance index at T4 were significantly decreased,and the expression of IRE1α,XBP1 and caspase-12 protein and mRNA was down-regulated at T4 in group Ⅰ (P＜0.05).Conclusion Exogenous insulin significantly improves insulin resistance in myocardial tissues,and the mechanism is related to inhibiting endoplasmic reticulum stress and reducing cell apoptosis in the rabbits undergoing CPB.
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Objective: To investigate the function of primary cilium as an oxygen sensor in PC12 cells. Methods: The PC12 cells were transfected with IFT88 siRNA. The nuclear translocation of hypoxia inducible factor-1α (HIF-1α), nuclear factor erythroid-2 related factor 2 (Nrf2), and ciliogenesis were observed by immunofluorescence staining; and the mRNA expressions of HIF-1α, Nrf2, vascular endothelial growth factor (VEGF) and superoxide dismutase (SOD) were detected by real-time RT-PCR. Results: The ciliogenesis was inhibited in PC12 cells transfected with IFT88 siRNA. In hypoxia group and scramble control group, nuclear translocations of HIF-1α and Nrf2 were observed and mRNA expressions of HIF-1α, Nrf2, VEGF were increased, and those of SOD were decreased. While in PC12 cells transfected with IFT88 siRNA, nuclear translocations of HIF-1α and Nrf2 were not observed, and mRNA expressions of HIF-1α, Nrf2, VEGF were inhibited, and mRNA expression of SOD was increased. Conclusion: Primary cilia may act as an oxygen sensor to transfer the information related to hypoxia and oxidative stress into cells, activating intracellular defense mechanism against the hypoxic injuries.
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Animals , Rats , Cilia , Metabolism , Gene Expression Regulation , Oxygen , Metabolism , PC12 CellsABSTRACT
ObjectiveTo investigate the effect of cardiopulmonary bypass (CPB) on the secretory function of islet cells in rabbits.MethodsTwenty adult New Zealand white rabbits of both sexes,weighing 2.5-3.0kg,were randomly divided into 2 groups ( n =10 each):sham operation group (group S) and CPB group.The rabbits were anesthetized with 3％ pentobarbital sodium 30 mg/kg.Blood samples were collected from the left femoral artery at 5 min after anesthesia (T1),immediately before CPB (T2 ),immediately after aortic clamping (T3 ),and at 5,35 and 75 min after aortic unclamping (T4-6) in the two groups for determination of levels of blood glucose,insulin and glucagons.Insulin resistance index was calculated.ResultsCompared with group S,the blood glucose concentration and levels of insulin and glucagons and insulin resistance index at T3-6 were significantly increased in group CPB ( P ＜ 0.05).ConclusionAlthough increase in blood glucose enhances the secretion of insulin in islet β cells,hyperglycemia cannot be compensated completely by the increased insulin during CPB in rabbits.The increase in blood glucose may be related to islet α cell resistance.
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ObjectiveTo investigate the effects of propofol on calcium/calmodulin-dependent protein kinase Ⅱ α ( CaMK Ⅱ α) activity in hippocampus in mentally depressed rats after electroconvulsive therapy (ECT).MethodsHealthy adult male SD rats aged 2-3 months weighing 180-220 g were used in this study.Mentally depressed model was induced by chronic unpredictable mild stress.Forty mentally depressed rats were randomly divided into 4 groups (n =10 each): mental depression group (group D),propofol group (group P),ECT group (group E),propofol + ECT group (group DPE).Groups D and P received intraperitoneal normal saline 8 ml/kg or propofol 80 mg/kg once a day for 7 consecutive days respectively.Group E received ECT once a day for 7 consecutive days.Group DPE received propofol 80 mg/kg + ECT once a day for 7 consecutive days.Sucrose preference test was performed at 1 d before and 1 d after treatment,and Morris water maze test was performed at 1 d before and 3 d after treatment.The rats were sacrificed after Morris water maze test,and hippocampi were removed for determination of CaMK Ⅱ α and phosphorylated CaMK Ⅱ α(pCaMK Ⅱ α )expression,and pCaMK Ⅱ α/CaMK Ⅱ α ratio was caculated.ResultsCompared with group D,the sucrose preference percentage was significantly increased in groups E and DPE,the escape latency prolonged and space exploration time shortened,and the expression of CaMK Ⅱ α and pCaMK Ⅱ α down-regulated,pCaMK Ⅱ α/CaMK Ⅱ α ratio decreased in group E,the escape latency was significantly shortened and space exploration time prolonged,and the expression of pCaMK Ⅱ α up-regulated in group DPE ( P ＜ 0.05).Compared with group E,the escape latency was significantly shortened,space exploration time prolonged,and the expression of CaMK Ⅱ α and pCaMK Ⅱ α up-regulated,and pCaMK Ⅱ α/CaMK Ⅱ α ratio increased in group DPE ( P ＜ 0.05).ConclusionPropofol can reduce the cognition impairment induced by ECT in mentally depressed rats through enhancing CaMK Ⅱ α activity in hippocampus.