1.Effects of N-acetylcysteine on caveolin-3 expression during myocardial ischemia-reperfusion in diabetic rats
Qiheng LIANG ; Zhongyuan XIA ; Wating SU ; Bo ZHAO ; Qiongxia ZHANG ; Yuan ZHANG ; Shaoqing LEI
Chinese Journal of Anesthesiology 2017;37(2):224-226
Objective To evaluate the effects of N-acetycysteine on the expression of caveolin-3 (Cav-3) during myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods Twenty-four pathogenfree healthy adult male Sprague-Dawley rats,weighing 230-270 g,were divided into 3 groups (n =8 each) using a random number table:myocardial I/R group (group I/R),diabetes mellitus plus myocardial I/R group (group D) and N-acetycysteine group (group NAC).Diabetes mellitus was induced by injection of streptozotocin 60 mg/kg via the tail vein and confirmed by blood glucose ≥ 16.7 mmol/L 3 days later.At 1 week after successful establishment of the model,N-acetycysteine 1.5 g · kg-1 · d-1 was injected through a gastric tube into stomach for 4 consecutive weeks in group NAC,and the equal volume of normal saline was given for 4 consecutive weeks in I/R and D groups.Myocardial I/R was then induced by 30 min ligation of the left anterior descending branch of the coronary artery followed by 2 h of reperfusion.At the end of reperfusion,the myocardial infarct size was determined by triphenyl tetrazolium chloride staining,the levels of serum creatine kinase-MB (CK-MB) and 15-F2t-Isoprostane were measured by enzyme-linked immunosorbent assay,and the expression of myocardial Cav-3,Akt,phosphor-Akt (p-Akt),endothelial nitric oxide synthase (eNOS) and phosphor-eNOS (p-eNOS) was detected by Western blot.Results Compared with group I/R,the myocardial infarct size and levels of serum CK-MB and 15-F2t-Isoprostane were significantly increased,and the myocardial Cav-3,p-Akt and p-eNOS expression and NO level were decreased in group D (P<0.05).Compared with group D,the myocardial infarct size and levels of serum CK-MB and 15-F2t-Isoprostane were significantly decreased,and the myocardial Car-3,p-Akt and p-eNOS expression and NO level were increased in group NAC (P<0.05).Conclusion N-acetycystein can activate Akt/eNOS/NO signaling pathway through up-regulating myocardial Cav-3 expression,thus reducing myocardial I/R injury in diabetic rats.
2.Role of caveolin 3 in diabetic cardiomyopathy in mice: relationship with endoplasmic reticulum stress
Yuefu ZHANG ; Lu ZHOU ; Wating SU ; Zhongyuan XIA ; Shaoqing LEI
Chinese Journal of Anesthesiology 2023;43(4):463-467
Objective:To evaluate the role of caveolin 3 (Cav-3) in diabetic cardiomyopathy and the relationship with endoplasmic reticulum stress in mice.Methods:This experiment was performed in two parts. Part Ⅰ in vivo experiment Sixteen clean-grade healthy adult male wild type mice weighing 18-20 g, were divided into 2 groups ( n=8 each) using a random number table method: control group(Control group) and diabetic cardiomyopathy group (DCM group). Another 8 Cav-3 KO mice were selected and served as Cav-3 KO + diabetic cardiomyopathy group (Cav-3 KO+ DCM group). Type 2 diabetic models were developed by high fat diet combined with intraperitoneal injection of streptozotocin (100 mg/kg). The left ventricular ejection fraction (EF), left ventricular short axis shortening rate (FS), left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) were measured by B ultrasound at 8 weeks. Then the mice were sacrificed, and the myocardial histomorphology was observed using HE staining. Part Ⅱ in vitro experiment HL-1 cardiomyocytes were divided into 3 groups ( n=6 each)using a random number table method: normal glucose group (NG group), high glucose group (HG group) and high glucose+ methyl-β-cyclodextrin group (HG+ β-CD group). The high glucose model was prepared by adding 50% glucose to a specialized culture medium until the final concentration reached 30 mmol/L, and HL-1 cardiomyocytes were continuously cultivated for 36 h. The cellular injury was assessed using LDH and CCK8 kits. The expression of endoplasmic reticulum stress-related proteins binding immunoglobulin protein (BiP), C/EBP-homologous protein (CHOP) and X-box binding protein 1 (XBP1-s) in myocardial tissues and HL-1 cells was detected by Western blot. Results:In vivo experiment Compared with Control group, the food intake, water intake, and heart mass/body mass were significantly increased, EF and FS were decreased, LVESD and LVEDD were increased, the expression of BiP, CHOP and XBP1-s was up-regulated, the expression of Cav-3 was down-regulated ( P<0.05), and the pathological damage was aggravated in DCM group and Cav-3 KO+ DCM group. Compared with DCM group, EF and FS were significantly decreased, LVESD and LVEDD were increased, the expression of BiP, CHOP and XBP1-s was up-regulated, the expression of Cav-3 was down-regulated ( P<0.05), and the pathological damage was aggravated in Cav-3 KO+ DCM group. In vitro experiment Compared with NG group, the cell viability was significantly decreased, LDH activity was increased, the expression of BiP, CHOP and XBP1-s was up-regulated, and the expression of Cav-3 was down-regulated in HG group and HG+ β-CD group ( P<0.05). Compared with HG group, the cell viability was significantly decreased, LDH was increased, the expression of BiP, CHOP and XBP1-s was up-regulated, and the expression of Cav-3 was down-regulated in HG+ β-CD group ( P<0.05). Conclusions:Down-regulation of Cav-3 expression aggravates myocardial injury in diabetes mellitus, and the mechanism is related to excessive activation of endoplasmic reticulum stress in mice.
3.Effect of hydromorphone on hemodynamics after general anesthesia in elderly patients with hypertension under evaluation of Bioz noninvasive monitoring system
Mingqian YANG ; Zhongyuan XIA ; Bo ZHAO ; Wating SU ; Ting HUANG
Journal of Clinical Medicine in Practice 2017;21(1):68-71
Objective To explore the effect of hydromorphone on hemodynamics after general anesthesia in elderly patients with hypertension under evaluation of Bioz noninvasive monitoring system.Methods Sixty elderly hypertension patients with selective abdominal operation under general anesthesia were randomly divided into hydromorphone group (HM group) and normal saline group (SP group),and 15 min before the end of surgery,hydromorphone was injected in the MH group,while the normal saline was injected in the control group.The indicators such as heart rate (HR),mean arterial pressure (MAP),cardiac output (CO),cardiac output index (CI) and systemic vascular resistance (SVR) were measured at different time points of before induction of anesthesia (T1),extubation (T2) and 10 min after extubation (T3).Recovery time of spontaneous breathing,awaking time,extubation time and out of PACU time were recorded.The visual analogue score (VAS),Ramsay sedation score at the PACU were also recorded at 5 min (H1),15 min (H2) and 30 min (H3).Results Compared with HM group,HR,MAP,SVR,VAS and Ramsay score increased significantly in the SP group (P < 0.05).Compared with the indexes at T1,HR,MAP,SVR increased significantly while CO,CI decreased significantly at T2 (P < 0.05).In both groups,SVR at T3 decreased but was significantly higher than that at T1 (P < 0.0 5).compared between two groups at H1 time point in PACU,VAS and Ramsay score in group SP at H2,H3 time point were no different (P > 0.05).VAS and Ramsay scores in HM group at H2,H3 were increased significantly (P <0.05).There were no significant differences in the recovery time of spontaneous breathing,awaking time and extubation time between two groups (P > 0.05).Conclusion Bioz non-invasive hemodynamic monitoring system can provide effective hemodynamic information,and subcutaneous injection of 1 mg hydromorphone before the end of operation can effectively maintain the hemodynamic stability during the recovery period of general anesthesia in elderly patients with hypertension.
4.Effect of hydromorphone on hemodynamics after general anesthesia in elderly patients with hypertension under evaluation of Bioz noninvasive monitoring system
Mingqian YANG ; Zhongyuan XIA ; Bo ZHAO ; Wating SU ; Ting HUANG
Journal of Clinical Medicine in Practice 2017;21(1):68-71
Objective To explore the effect of hydromorphone on hemodynamics after general anesthesia in elderly patients with hypertension under evaluation of Bioz noninvasive monitoring system.Methods Sixty elderly hypertension patients with selective abdominal operation under general anesthesia were randomly divided into hydromorphone group (HM group) and normal saline group (SP group),and 15 min before the end of surgery,hydromorphone was injected in the MH group,while the normal saline was injected in the control group.The indicators such as heart rate (HR),mean arterial pressure (MAP),cardiac output (CO),cardiac output index (CI) and systemic vascular resistance (SVR) were measured at different time points of before induction of anesthesia (T1),extubation (T2) and 10 min after extubation (T3).Recovery time of spontaneous breathing,awaking time,extubation time and out of PACU time were recorded.The visual analogue score (VAS),Ramsay sedation score at the PACU were also recorded at 5 min (H1),15 min (H2) and 30 min (H3).Results Compared with HM group,HR,MAP,SVR,VAS and Ramsay score increased significantly in the SP group (P < 0.05).Compared with the indexes at T1,HR,MAP,SVR increased significantly while CO,CI decreased significantly at T2 (P < 0.05).In both groups,SVR at T3 decreased but was significantly higher than that at T1 (P < 0.0 5).compared between two groups at H1 time point in PACU,VAS and Ramsay score in group SP at H2,H3 time point were no different (P > 0.05).VAS and Ramsay scores in HM group at H2,H3 were increased significantly (P <0.05).There were no significant differences in the recovery time of spontaneous breathing,awaking time and extubation time between two groups (P > 0.05).Conclusion Bioz non-invasive hemodynamic monitoring system can provide effective hemodynamic information,and subcutaneous injection of 1 mg hydromorphone before the end of operation can effectively maintain the hemodynamic stability during the recovery period of general anesthesia in elderly patients with hypertension.