OBJECTIVE To evaluate the cost-effectiveness of apatinib combined with adriamycin in the second-line chemotherapy of platinum-resistant recurrent ovarian cancer （OC） from the perspective of the health system in China. METHODS A three-state partitioned survival model was constructed based on the APPROVE clinical trial and related literature data， with a model simulation time frame of 10 years and a 4-week cycle， and both cost and utility values were discounted using a 5% discount rate. Cost and quality-adjusted life years （QALYs） were used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the cost-effectiveness of apatinib combined with adriamycin versus adriamycin chemotherapy in the second-line treatment of platinum-resistant recurrent OC. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS The results of base-case analysis indicated that compared with chemotherapy alone， ICER of patients receiving apatinib combined with adriamycin was 124 678.25 yuan/QALY， which was less than willingness-to-pay （WTP） threshold set in this study [3 times per capita gross domestic product （GDP） of China in 2022 （257 094 yuan）]. The results of scenario analysis showed that， with the extension of the simulation time limit， the ICER of apatinib combined with adriamycin was gradually reduced， and the decline was gradually reduced， but both were less than WTP threshold. The results of single factor sensitivity analysis showed that the factors that had the greatest impact on ICER were the utility value of progression， body surface area， discount rate，and the cost of best supportive treatment， etc. The results of probability sensitivity analysis showed that under WTP threshold set in this study， the economic probability of apatinib combined with adriamycin was about 99%. CONCLUSIONS From the perspective of China’s health system， using three times the per capita GDP in 2022 as the WTP threshold， the combination of apatinib and adriamycin is more cost-effective than adriamycin alone in second-line chemotherapy for platinum-resistant recurrent OC.

Objective:To evaluate the effect of SR9009 on myocardial injury in endotoxemic mice.Methods:Eighteen SPF healthy male C57BL/6 mice, aged 5 weeks, weighing 21-24 g, were divided into 3 groups ( n=6 each) by the random number table method: control group (C group), endotoxemia group (lipopolysaccharide [LPS] group) and endotoxemia + SR9009 group (LPS+ SR group). SR9009 50 mg/kg was intraperitoneally injected at 4: 00 p. m. in LPS+ SR group. The endotoxemic model was prepared by intraperitoneal injection of LPS 15 mg/kg at 10 a. m. on the second day in mice. The left ventricular function was monitored by echocardiography at 9 h after LPS injection. Blood samples were collected from the heart cavity under direct visualization for determination of the serum creatine kinase isoenzymes (CK-MB), lactic dehydrogenase (LDH) and cardiac troponin I (cTnI) levels by enzyme-linked immunosorbent assay. Myocardial tissues were obtained and stained with HE for microscopic examination of the pathological changes (with a light microscope) and for determination of the expression of Beclin1, P62 and microtubule-associated protein 1 light cain 3 (LC3) (by Western blot), and the ratio of LC3Ⅱ to LC3Ⅰ was calculated. Results:Compared with group C, the ejection fraction and short-axis fractional shortening were significantly decreased, the left ventricular end-diastolic internal diameter and left ventricular end-systolic internal diameter were shortened, the left ventricular end-diastolic posterior wall thickness and left ventricular end-systolic posterior wall thickness were decreased, serum CK-MB, LDH and cTnI levels were increased, P62 expression in myocardial tissues was down-regulated, Beclin1 expression was up-regulated, LC3Ⅱ/LC3Ⅰ ratio was increased ( P<0.05), and the pathological changes were found in myocardial tissues in group LPS. Compared with group LPS, the ejection fraction and short-axis fractional shortening were significantly increased, the left ventricular end-systolic internal diameter was shortened, and the left ventricular end-diastolic posterior wall thickness was decreased ( P<0.05), no significant change was found the left ventricular end-diastolic internal diameter and left ventricular posterior end-systolic wall thickness ( P>0.05), the serum CK-MB, LDH and cTnI levels were decreased, and P62 expression in myocardial tissues was up-regulated, Beclin1 expression was down-regulated, LC3Ⅱ/LC3Ⅰ ratio was decreased ( P<0.05), and the pathological changes in myocardial tissues were significantly attenuated in LPS+ SR group. Conclusions:SR9009 can alleviate myocardial injury in endotoxemic mice, and the mechanism may be related to inhibition of autophagy.

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.

Objective:To evaluate the effect of verbascoside on cold ischemia-reperfusion injury following heterotopic heart transplantation in mice and the relationship with nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) signaling pathway.Methods:This experiment was performed in two parts. Part Ⅰ animal experiment Eighteen SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 24-28 g, were divided into 3 groups ( n=6 each) by the random number table method: control group (C group), cold ischemia-reperfusion (I/R) group (I/R group) and cold I/R + verbascoside group (I/R+ VB group). Cold I/R injury model of mouse heart transplantation was prepared by neck heterotopic heart transplantation using the modified non-suture cuff technique. The donor heart in group C was immediately transplanted to the recipient after removal, while the donor heart in group I/R was stored in the 4 ℃ University of Wisconsin solution for 8 h before transplantation to the recipient, and verbascoside 20 mg/kg was intraperitoneally injected at 3 days before surgery in donor and recipient mice in I/R+ VB group. At the end of reperfusion, the myocardial tissue of the transplanted heart was obtained after assessing the beating score for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity by enzyme-linked immunosorbent assay. Part of the donor myocardium was taken for examination of the pathological results. The expression of NF-κB, p-NF-κB, NOD-like receptor protein 3 (NLRP3), ACS and caspase-1 was detected by Western blot. The expression of IL-1β, TNF-α and IL-6 mRNA was detected by real-time polymerase chain reaction. Part Ⅱ cell experiment Rat cardiomyocyte H9c2 cold hypoxia-reoxygenation model was developed, and the cells were divided into 3 groups ( n=24 each) by the random number table method: control group (C group), cold hypoxia-reoxygenation group (H/R group), and cold hypoxia-reoxygenation+ verbascoside group (H/R+ VB group). The cells were exposed to hypoxia for 18 h at 10 ℃ followed by restoration of reoxygenation for 24 h at 37 ℃ to develop the cold hypoxia-reoxygenation model. The cell viability and LDH activity were determined. The expression of NF-κB and NLRP3 was detected by Western blot, and the expression of phosphorylated NF-κB (p-NF-κB) was detected by immunofluorescence staining. Results:Part Ⅰanimal experiment Compared with C group, the MDA content was significantly increased, the beating score of grafts and SOD activity were decreased, and the expression of p-NF-κB, NLRP3, ACS and caspase-1 and IL-1β, TNF-α and IL-6 mRNA was up-regulated ( P<0.05), and myocardial histopathological injury was aggravated in I/R group. Compared with I/R group, the content of MDA was significantly decreased, the beating score of grafts and SOD activity were increased, the expression of p-NF-κB, NLRP3, ACS and caspase-1 and IL-1β, TNF-α and IL-6 mRNA was down-regulated ( P<0.05), and the myocardial histopathological injury was alleviated in I/R+ VB group. Part Ⅱ cell experiment Compared with C group, the cell viability was significantly decreased, the activity of LDH was increased, and the expression of p-NF-κB, NLRP3, ACS, caspase-1 and p-NF-κB was up-regulated in H/R group ( P<0.05). Compared with H/R group, the cell viability was significantly increased, the activity of LDH was decreased, and the expression of p-NF-κB, NLRP3, ACS, caspase-1 and p-NF-κB was down-regulated in H/R+ VB group ( P<0.05). Conclusions:Verbascoside can alleviate cold I/R injury following heterotopic heart transplantation in mice, and the mechanism may be related to inhibition of activation of NF-κB/NLRP3 signaling pathway.

Objective:To evaluate the role of nuclear receptor subfamily 1, group D, member 1/brain and muscle Arnt-like 1(Rev-erbα/Bmal1) signaling pathway in myocardial ischemia-reperfusion (I/R) injury in diabetic rats and its relationship with autophagy.Methods:SPF-grade adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-220 g, were used in this study.Type I diabetes mellitus was induced by intraperitoneal streptozotocin 60 mg/kg.The rats were continuously fed for 8 weeks after successful establishment of the model.Thirty rats with type 1 diabetes mellitus were divided into 3 groups by a random number table method: diabetic sham operation group (DS group, n=6), diabetic myocardial I/R group (DI/R group, n=12) and diabetic myocardial I/R plus Rev-erbα antagonist SR-8278 group (DI/R+ SR group, n=12). Eighteen non-diabetic rats were divided into 2 groups by a random number table method: non-diabetic sham operation group (NS group, n=6) and non-diabetic myocardial I/R group (NI/R group, n=12). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion in anesthetized rats.SR-8278 2 mg/kg was intravenously injected via the femoral vein at 1 h before ischemia in group DI/R+ SR.Blood samples were collected from the carotid artery immediately after the end of reperfusion for determination of serum troponin I (cTnI), creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) levels (by enzyme-linked immunosorbent assay). Then the rats were sacrificed, and myocardial tissues were obtained for determination of myocardial infarct size (by TTC method), expression of Rev-erbα and Bmal1 mRNA (by real-time polymerase chain reaction) and expression of Rev-erbα, Bmal1, microtubule-associated protein 1 light chain (LC3) Ⅱ and LC3Ⅰ (by Western blot) and for calculation of the ratio of LC3 Ⅱ/LC3Ⅰand the number of autophagosomes (with a transmission electron microscope). Results:Compared with group NS, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were significantly increased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group NI/R, and serum levels of cTnI, CK-MB and LDH were increased, the number of autophagosomes was decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated and the ratio of LC3 Ⅱ/LC3Ⅰwas decreased in group DS ( P<0.05). Compared with group NI/R, the percentage of myocardial infarct size and serum levels of cTnI, CK-MB and LDH were significantly increased, the number of autophagosomes was decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas decreased in group DI/R ( P<0.05). Compared with group DS, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were were significantly increased, the expression of Rev-erbα and its mRNA in myocardial tissues was up-regulated, the expression of Bmall and its mRNA was down-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group DI/R ( P<0.05). Compared with group DI/R, the percentage of myocardial infarct size, serum levels of cTnI, CK-MB and LDH and the number of autophagosomes were significantly decreased, the expression of Rev-erbα and its mRNA in myocardial tissues was down-regulated, the expression of Bmall and its mRNA was up-regulated, and the ratio of LC3 Ⅱ/LC3Ⅰwas increased in group DI/R+ SR ( P<0.05). Conclusion:Rev-erbα/BMAL1 signaling pathway is involved in the process of myocardial I/R injury by regulating cell autophagy in diabetic rats.

Objective:To evaluate the role of histone deacetylase 3 (HDAC3) in high glucose hypoxia/reoxygenation (H/R) injury to primary rat cardiomyocytes and the relationship with autophagy.Methods:The primary cardiomyocytes extracted from newborn Sprague-Dawley rats, aged about 1-3 days, were divided into 5 groups ( n=24 each) according to the random number table method: control group (C group, glucose concentration 5.5 mmol/L), H/R group, high glucose group (H group, glucose concentration 30 mmol/L), high glucose H/R group (HH/R group), and high glucose H/R + HDAC3 inhibitor RGFP966 group (HH/R+ RG group). Fifty percent glucose injection was used to prepare high-glucose medium (final concentration 30 mmol/L). Cells were cultured in a hypoxic environment (5% CO 2-0.9% O 2-94.1% N 2) for 6 h, followed by reoxygenation in a normoxic environment for 2 h to establish the cardiomyocyte H/R model in H/R group.RGFP966 at a final concentration of 10 μmol/L was added at 24 h before H/R in HH/R+ RG group.At 2 h of reoxygenation, the cell viability was measured using CCK-8 kit, the activity of lactic dehydrogenase (LDH) in the cell supernatant was determined using enzyme-linked immunosorbent assay, the level of autophagy was detected with a confocal microscope after cells were transfected with autophagy double-labeled adenovirus (mRFP-GFP-LC3), and the expression of HDAC3, p62, LC3 Ⅱ and LC3 Ⅰ was detected using Western blot.LC3Ⅱ/LC3Ⅰ ratio was calculated. Results:Compared with group C, the cell viability was significantly decreased, and the activity of LDH in supernatant was increased in H/R and H groups, the number of autophagosomes was significantly increased, the expression of HDAC3 in cardiomyocytes was up-regulated, the expression of p62 was down-regulated, and the LC3 Ⅱ/I ratio was increased in group H/R, and the number of autophagosomes was significantly decreased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was decreased in group H ( P<0.05). Compared with group H/R, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, the number of autophagosomes was decreased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was decreased in group HH/R ( P<0.05). Compared with group H, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, the number of autophagosomes was increased, the expression of HDAC3 and p62 in cardiomyocytes was up-regulated, and the LC3 Ⅱ/I ratio was increased in group HH/R ( P<0.05). Compared with group HH/R, the cell viability was significantly increased, the activity of LDH in supernatant was decreased, the number of autophagosomes was increased, the expression of HDAC3 and p62 in cardiomyocytes was down-regulated, and the LC3 Ⅱ/I ratio was increased in group HH/R+ RG ( P<0.05). Conclusion:Up-regulation of HDAC3 expression is involved in high glucose H/R injury to primary rat cardiomyocytes, which is related to decreasing the level of autophagy.

Objective: To evaluate the role of histone deacetylase 3 (HDAC3) in renal injury induced by myocardial ischemia-reperfusion (I/R) in diabetic rats. Methods: SPF healthy adult male Sprague-Dawley rats, weighing 210-220 g, were used in this study.Diabetes mellitus was induced by intraperitoneal injection of 1% streptozotocin 60 mg/kg.Eighteen diabetic rats were divided into 3 groups (n=6 each) using a random number table method: sham operation group (group S), group I/R and HDAC3 inhibitor RGFP966 group (RG). The myocardial I/R model was established by ligation of the left anterior descending coronary artery for 30 min followed by 120-min reperfusion.RGFP966 10 mg/kg was intraperitoneally injected at 1 h before myocardial ischemia in group RG.The right internal carotid artery was isolated at 120 min of reperfusion for measurement of serum lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), creatinine (Cr) and urea nitrogen concentrations.Renal tissues were obtained for examination of the pathological changes and for determination of the expression of HDAC3, silent information regulator 1 (SIRT1) and interleukin-1β (IL-1β). The damage to the renal tubules was scored. Results: Compared with S group, the serum LDH, CK-MB, Cr and urea nitrogen concentrations and renal tubular damage score were significantly increased, the expression of HDAC3 and IL-1β was up-regulated, and the expression of SIRT1 was down-regulated in group I/R (P<0.05). Compared with group I/R, the serum LDH, CK-MB, Cr and urea nitrogen concentrations and renal tubular damage score were significantly decreased, the expression of HDAC3 and IL-1β was down-regulated, and the expression of SIRT1 was up-regulated in group RG (P<0.05). Conclusion Up-regulated expression of HDAC3 is involved in renal injury induced by myocardial I/R in diabetic rats.

Objective To evaluate the effect of tyrosol on myocardial ischemia-reperfusion (I/R) injury in diabetic rats and the role of silent mating-type information regulation 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/endothelial nitric oxide synthase (eNOS) signaling pathway.Methods SPF healthy adult male Sprague-Dawley rats,weighing 200-220 g,were intraperitoneally injected with streptozotocin 60 mg/kg to establish the model of diabetes mellitus.Fifty-six diabetic rats were divided into 4 groups (n =14 each) using a random number table method:sham operation group (S group),myocardial I/R group (I/R group),myocardial I/R plus tyrosol group (I/R+T group),and myocardial I/R plus tyrosol plus SIRT1 inhibitor EX527 group (I/R+T+E group).In I/R+T and I/R+T+E groups,tyrosol 20 mg · kg-1 · d-1 was given by gavage for 45 consecutive days,and the equal volume of normal saline was given in the other two groups.In I/R+T+E group,EX527 5 mg · kg-1 · d-1 was intraperitoneally injected for 3 consecutive days before ischemia,and EX527 5 mg/kg was intraperitoneally injected at 20 min before repeffusion.Myocardial I/R was induced by ligation of the left anterior descending branch of coronary artery for 30 min followed by 2-h reperfusion.The myocardial infarct volume was measured by TTC staining.The levels of creatine kinase-MB (CK-MB),lactic dehydrogenase (LDH) and 5-F2t-isoprostane in serum and superoxide dismutase (SOD) in myocardial tissues were detected by enzyme-linked immunosorbent assay.The expression of SIRT1,AMPK,phosphorylated AMPK (p-AMPK),eNOS and p-eNOS was detected by Western blot.Results Compared with S group,the levels of serum CK-MB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly increased,the SOD activity was decreased,and the SIRT1 expression was down-regulated in I/R group,and the levels of serum CKMB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly increased,the SOD activity was decreased,the SIRT1 expression was down-regulated,and the expression of p-AMPK and peNOS was up-regulated in I/R+T and I/R+T+E groups (P＜0.05).Compared with I/R group,the levels of serum CK-MB,LDH and 15-F2t-Isoprostane and myocardial infarction volume were significantly decreased,the SOD activity was increased,and the expression of SIRT1,p-AMPK and p-eNOS was up-regulated in I/R+T group (P＜0.05),and no significant change was found in the parameters mentioned above in I/R+ T+E group (P＞0.05).Compared with I/R+T group,the levels of CK-MB,LDH and 15-F2t-isoprostane in serum and myocardial infarct volume were significantly increased,the SOD activity was increased,and the expression of SIRT1,p-AMPK and p-eNOS was down-regulated in I/R+T+E group (P＜0.05).Conclusion Tyrosol can mitigate myocardial I/R injury,and the mechanism may be related to activating SIRT1/AMPK/eNOS signaling pathway and inhibiting oxidative stress response in diabetic rats.

Objective To evaluate the role of NOD-like receptor 3 (NLRP3) inflammasome in pyroptosis during myocardial ischemia-reperfusion (I/R) in diabetic rats.Methods SPF male Sprague-Dawley rats,aged 6-8 weeks,weighing 210-230 g,were studied.Type 1 diabetes mellitus (DM) was induced by intraperitoneal injection of 1％ streptozotocin 60 mg/kg.Forty-two rats with type 1 DM were divided into 4 groups using a random number table method:sham operation group (DS group,n =6),myocardial I/R group (DI/R group,n =12),myocardial I/R plus caspase-1 inhibitor Ac-YVAD-CMK group (DI/R+Ac group,n=12) and myocardial I/R plus NLRP3 inhibitor BAY11-7082 group (DI/R+BAY group,n=12).Eighteen healthy adult male Sprague-Dawley rats were selected and randomly divided into sham operation group (group S,n =6) and myocardial I/R group (group I/R,n =12).Myocardial I/R was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion at 8 weeks after successful establishment of the type 1 DM model.Ac-YVAD-CMK 1.5 mg/kg and BAY1 1-7082 5 mg/kg were intraperitoneally injected at 10 min before reperfusion in DI/R+Ac group and DI/R+BAY group,respectively.At the end of reperfusion,the myocardial infarct size was measured using TTC staining,the activities of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in serum were detected by enzyme-linked immunosorbent assay,the ultrastructure of myocardium was observed by transmission electron microscopy,and the expression of NLRP3,pro-caspase-1,caspase-1,apoptosis-associated speck-like protein containing CARD (ASC) and interleukin-1 (IL-1β) in myocardial tissues was detected by Western blot.Results Compared with group S or group DS,the activities of serum CK-MB and LDH were significantly increased,and the expression of NLRP3,pro-caspase-1,caspase-1,ASC and IL-1β was down-regulated in I/R and DI/R groups (P＜0.05).Compared with group DI/R,the percentage of myocardial infarct size and activities of serum CK-MB and LDH were significantly decreased,and the expression of NLRP3,pro-caspase-1,caspase-1,ASC and IL-1β was down-regulated in group I/R,the percentage of myocardial infarct size and activities of serum CK-MB and LDH were significantly decreased,and the expression of pro-caspase-1,ASC and IL-1 β was down-regulated in group DI/R+Ac,and the percentage of myocardial infarct size and activities of serum CK-MB and LDH were significantly decreased,and the expression of NLRP3,pro-caspase-1,caspase-1,ASC and IL-1β was down-regulated (P＜0.05),and the pathological changes of myocardium were significantly attenuated in group DI/R+BAY.Conclusion The mechanism of pyroptosis during myocardial I/R may be related to the activation of NLRP3 inflammasome in diabetic rats.

Objective To evaluate the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in diabetes mellitus-induced reduction of hypoxic postconditioning (HPO)-induced protection of cardiomyocytes and the relationship with glycogen synthase kinase-3β (GSK-3β)-mediated mitochondrial apoptotic pathway.Methods H9c2 cells incubated in high-glucose (30 mmol/L) medium for 24 h were divided into 6 groups (n =5 each) using a random number table:normoxia group (group N),hypoxia-reoxygenation (H/R) group,group HPO,PTEN gene silencing normoxia group (group P-N),PTEN gene silencing H/R group (group P-H/R),and PTEN gene silencing HPO group (group P-HPO).H9c2 cells were exposed to 95％ N2-5％ CO2 for 4 h followed by 2 h reoxygenation with 90％ O2-10％ CO2.HPO was induced by 3 cycles of 5 min reoxygenation followed by 5 min hypoxia before reoxygenation.At the end of reoxygenation,the level of lactate dehydrogenase (LDH) in the supernatant was detected by enzyme-linked immunosorbent assay,the changes in mitochondrial membrane potential (MMP were assessed by JC-1 fluorescence assay,the cell apoptosis was detected by AnnexinV-FITC/PI flow cytometry,and the expression of PTEN and phosphorylated GSK-3β (p-GSK-3β) was determined by Western blot.The JC-1 monomer/polymer ratio and apoptosis rate were calculated.Results Compared with group N,the amount of LDH released,JC-1 monomer/polymer ratio and apoptosis rate were significantly increased,and the expression of PTEN was up-regulated in H/R and HPO groups (P＜0.05).There was no significant difference in the parameters mentioned above between group H/R and group HPO (P＞0.05).Compared with group HPO,the amount of LDH released,JC-1 monomer/polymer ratio and apoptosis rate were significantly decreased,PTEN expression was down-regulated,and the expression of p-GSK-3β was up-regulated in group P-HPO (P＜0.05).Compared with group N,the expression of PTEN was significantly down-regulated,and no significant changes were found in the other parameters mentioned above in group P-N (P＞0.05).Compared with group H/R,the expression of PTEN was significantly down-regulated,and no significant changes were found in the other parameters mentioned above in group P-H/R (P＞0.05).Conclusion PTEN is involved in diabetes mellitus-induced reduction of HPO-induced protection of cardiomyocytes,and the mechanism is associated with PTEN-induced activation of GSK-3β-modulated mitochondrial apoptotic pathway.