Objective To evaluate the role of serine-threonine kinase (Akt)/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway in isoflurane preconditioning-induced inhibition of mitochondrial permeability transition pore protein (mPTP) opening during myocardial ischemia-reperfusion (I/R) in rats.Methods Ninety-six male Sprague-Dawley rats,aged 3-4 months,weighing 200-250 g,were randomly divided into 4 groups (n =24 each) using a random number table:control group (group C);I/R group;isoflurane preconditioning group (group IPC);Akt inhibitor MK-2206 group (group MK).Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 2 h of reperfusion.In group IPC,1.5％ isoflurane was inhaled for 30 min followed by 45 min washout,and then the model of myocardial I/R injury was established.In group MK,MK-2206 300 μg/kg (in dimethyl sulfoxide) was injected intraperitoneally at 30 min before isoflurane inhalation.At 2 h of reperfusion,8 rats were selected and sacrificed,and the hearts were removed for determination of myocardial infarct size.At 2 h of reperfusion,8 rats were selected,and blood samples were collected from the right internal jugular vein for determination of serum cardiac troponin Ⅰ (cTnI) concentrations.The rats were then sacrificed,and myocardial specimens were obtained for determination of the expression of phosphorylated GSK-3β (p-GSK-3β) in cytoplasm and mitochondria (by Western blot) and co-expression of p-GSK-3β with adenine nucleotide translocator (ANT),voltage-dependent anion channel or cyclophilin D in myocardial tissues (using co-immunoprecipitation).At 2 h of reperfusion,8 rats were selected and sacrificed,myocardial cells were obtained,and the opening time of mPTP was determined with a laser scanning confocal microscope.Results Compared with group C,the myocardial infarct size and serum cTnI concentrations were significantly increased,and the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated in I/R and IPC groups,the co-expression of p-GSK-3β with ANT was significantly down-regulated,and the opening time of mPTP was shortened in group I/R,and the co-expression of p-GSK-3β with ANT was significantly up-regulated,and the opening time of mPTP was prolonged in group IPC (P＜0.05).Compared with group I/R,the myocardial infarct size and serum cTnI concentrations were significantly decreased,the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated,the co-expression of p-GSK-3β with ANT was significantly up-regulated,and the opening time of mPTP was prolonged in group IPC,and the opening time of mPTP was significantly prolonged (P＜0.05),and no significant change was found in the other parameters in group MK (P＞0.05).Compared with group IPC,the myocardial infarct size and serum cTnI concentrations were significantly increased,the expression of p-GSK-3β in cytoplasm and mitochondria was up-regulated,the co-expression of p-GSK-3β with ANT was significantly down-regulated,and the opening time of mPTP was shortened in group MK (P＜0.05).No co-expression of p-GSK-3β with voltage-dependent anion channel or cyclophilin D was found in myocardial tissues.Conclusion The mechanism by which isoflurane preconditioning inhibits mPTP opening during myocardial ischemia-reperfusion is partially related to activation of Akt/GSK-3β signaling pathway in rats.

Objective: To evaluate the effect of nicotinamide adenine dinucleotide phosphate (NADPH) on myocardial ischemia-reperfusion (I/R) injury in rats. Methods: Fifty-six SPF adult male Sprague-Dawley rats, weighing 220-320 g, aged 1-2 months, were divided into 4 groups (n=14 each) using a random number table method: sham operation group (Sham group), myocardial I/R group (I/R group), NADPH group (N group) and diltiazem group (D group). The model of myocardial I/R injury was established by ligation of the left anterior descending branch for 30 min followed by 2-h reperfusion in anesthetized rats.NADPH 16 mg/kg was intravenously infused over 5 min starting from 5 min of reperfusion in N group.Diltiazem 5 mg/kg was infused through the internal jugular vein starting from 10 min before ischemia until the end of ischemia.At 2 h of reperfusion, blood samples were taken from the internal jugular vein for measurement of serum LDH and cTnI concentrations, and myocardial tissues were taken for determination of infarct size and ROS level. Results: Compared with Sham group, the serum LDH and cTnI concentrations, myocardial infarction size and ROS levels were significantly increased in I/R group (P<0.05). Compared with I/R group, the serum LDH and cTnI concentrations, myocardial infarction size and ROS levels were significantly decreased in N and D groups (P<0.05). Compared with N group, the LDH concentration was significantly decreased (P<0.05), and no significant change was found in the cTnI concentration, myocardial infarction size or ROS level in D group (P>0.05). Conclusion NADPH can reduce myocardial I/R injury through antioxidant effect in rats.

Objective To evaluate the effect of nicotinamide adenine dinucleotide phosphate(NADPH)on myocardial ischemia-reperfusion(I/R)injury in rats.Methods Fifty-six SPF adult male Sprague-Dawley rats,weighing 220-320 g,aged 1-2 months,were divided into 4 groups(n＝14 each)using a random number table method: sham operation group(Sham group),myocardial I/R group(I/R group),NADPH group(N group)and diltiazem group(D group).The model of myocardial I/R injury was established by ligation of the left anterior descending branch for 30 min followed by 2-h reperfusion in anesthetized rats.NADPH 16 mg/kg was intravenously infused over 5 min starting from 5 min of reperfusion in N group.Diltiazem 5 mg/kg was infused through the internal jugular vein starting from 10 min before is-chemia until the end of ischemia.At 2 h of reperfusion,blood samples were taken from the internal jugular vein for measurement of serum LDH and cTnI concentrations,and myocardial tissues were taken for deter-mination of infarct size and ROS level.Results Compared with Sham group,the serum LDH and cTnI concentrations,myocardial infarction size and ROS levels were significantly increased in I/R group(P＜0.05).Compared with I/R group,the serum LDH and cTnI concentrations,myocardial infarction size and ROS levels were significantly decreased in N and D groups(P＜0.05).Compared with N group,the LDH concentration was significantly decreased(P＜0.05),and no significant change was found in the cTnI con-centration,myocardial infarction size or ROS level in D group(P>0.05).Conclusion NADPH can re-duce myocardial I/R injury through antioxidant effect in rats.

Objective:To identify the risk factors for postoperative septic cardiomyopathy (SCM) in septic patients.Methods:The perioperative medical records of septic patients admitted to the intensive care unit (ICU) of Second Affiliated Hospital of Soochow University, First Affiliated Hospital of Soochow University and Suzhou Municipal Hospital after surgery from January 2017 to November 2020 were retrospectively collected.The patients were divided into SCM group and non-SCM group (NSCM group) according to whether or not SCM developed within 48 h after operation.Multivariate logistic regression analysis was used to identify the risk factors for SCM.Results:A total of 269 patients were included in this study, including 49 patients in SCM group and 220 patients in NSCM groups.Compared with group NSCM, the rate of laparoscopic surgery, the Sequential Organ Failure Assessment (SOFA) at the time of entering ICU, the serum concentration of lactate at the time of entering ICU, the highest serum concentration of lactate, the highest serum concentration of procalcitonin, the maximum consumption of norepinephrine and the highest body temperature were increased, and the minimum platelet count was decreased in group SCM ( P<0.1). The results of logistic regression analysis showed that SOFA score at the time of entering ICU and laparoscopic surgery were the risk factors for the development of postoperative SCM in septic patients ( P<0.05). The risk for SCM was increased by 34.273 times when the SOFA score at the time of entering ICU was ≥7 ( P<0.05). Conclusion:Laparoscopic surgery and SOFA score ≥7 at the time of entering ICU are the risk factors for the development of postoperative SCM in septic patients.

BACKGROUND:Studies have found that nicotine can activate the dopamine system,slowing the progression of Parkinson's disease,but the specific mechanism is still unclear.Research on the neuroprotective mechanism of nicotine in animal models of Parkinson's disease is lacking. OBJECTIVE:To investigate the neuroprotective effect of nicotine on rotenone-induced Parkinson's disease in mice. METHODS:Twenty-eight C57BL/6 mice were randomly divided into vehicle group,rotenone group,autophagy agonist group and nicotine group,with seven mice in each group.Dopaminergic nerve damage was induced by rotenone in C57BL/6 mice,and the autophagy agonist(rapamycin)or nicotine was given before modeling.The spatial exploration function of the mice was observed by open field test.Western blot and Q-PCR were used to detect the expression of α-synuclein,autophagy related factors Beclin-1 and P62,and apoptosis-related factors Bax,Bcl-2 and Cleaved-caspase3 in the nigra of each group.The deposition of mitochondria,autophagosomes and lipofuscin in nigra cells were observed by transmission electron microscopy.The survival of neurons was observed by Nissl staining.The expression of tyrosine hydroxylase was observed by immunofluorescence and immunohistochemical staining. RESULTS AND CONCLUSION:The open field test showed that the distance,average speed and time of movement were reduced in the rotenone group compared with the solvent group.Compared with the rotenone group,the exercise distance,average speed and exercise time of mice were increased in the nicotine group and autophagy agonist group(P＜0.05).The results of immunofluorescence and immunohistochemistry showed that the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase in the rotenone group decreased compared with that in the solvent group.Compared with the rotenone group,the mean fluorescence intensity and mean absorbance value of tyrosine hydroxylase were increased in the nicotine group and autophagy agonist group.Western blot and Q-PCR results showed that compared with the solvent group,the expressions of α-synuclein and P62 in the rotenone group were increased,while Beclin-1 expression was decreased(P＜0.05);compared with the rotenone group,the expression of α-synuclein and P62 decreased in the nicotine group and autophagy agonist group,and the expression of Beclin-1 increased(P＜0.05).Compared with the solvent group,the expressions of Bax and Cleaved caspase3 were increased and Bcl-2 expression was decreased in the rotenone group(P＜0.05);compared with the rothenone group,the expressions of Bax and Cleaved-caspase3 were decreased and the expression of Bcl-2 was increased in the nicotine and autophagy agonist groups(P＜0.05).To conclude,nicotine may have a dopaminergic neuroprotective effect on rotenone-induced Parkinson's disease mouse models by improving autophagy dysfunction and reducing apoptosis.