ObjectiveTo investigate the effects of dapagliflozin, in addition to standard therapy, on heart rate variability (HRV), soluble growth stimulation expressed gene 2 protein (sST2), N-terminal pro B-type natriuretic peptide (NT-proBNP), and echocardiographic parameters in patients with early-onset post-myocardial infarction heart failure (HF).MethodsA total of 98 patients with early-onset post-myocardial infarction HF were enrolled and randomly divided into a control group (n = 48, receiving standard therapy) and an observation group (n = 50, receiving standard therapy plus dapagliflozin 10 mg daily). HRV, cardiac function, and echocardiographic parameters were measured at baseline and after 24 weeks of treatment. Short-term prognosis and adverse events were also monitored.ResultsCompared with the control group, the observation group showed significantly greater improvements in SDNN and SDANN (P < 0.05). Significant improvements were also observed in sST2 and NT-proBNP levels in the observation group compared to the control group (P < 0.05). Additionally, echocardiographic parameters, including EF, LVESD, LVEDD, IVST, LVMI, and E/e’, showed greater improvement in the observation group (P < 0.05). The incidence of major adverse cardiovascular events was lower in the observation group (P < 0.05). Multivariate logistic regression model revealed that dapagliflozin use was independently associated with a reduced risk of MACE (OR = 0.265, 95% CI: 0.097–0.724, P = 0.010).ConclusionEarly administration of dapagliflozin 10 mg, in addition to standard therapy, can improve autonomic function, cardiac function, and short-term prognosis in patients with early-onset post-myocardial infarction heart failure.

BACKGROUND:Dapagliflozin is a selective SGLT2 inhibitor, which has been widely used in the treatment of patients with type 2 diabetes mellitus (T2DM). By blocking the reabsorption of glucose in renal tubules, daglitazine can promote urinary glucose excretion, reduce blood glucose and blood pressure, and also shows a protective effect on the heart in clinical studies. Accordingly, this study was designed to explore the effects of dapagliflozin on cardiac function and short-term prognosis of patients with acute myocardial infarction (AMI) complicated with T2DM. METHODS:The clinical data of 100 patients with both AMI and T2DM treated at Shibei Hospital of Jingan District from January 2021 to January 2023 were analyzed retrospectively. Totally 47 patients treated with hypoglycemic agents other than SGLT-2i inhibitors on the basis of routine treatment were assigned to the control group, and 53 patients treated with dapagliflozin based on treatment of the control group were assigned to the study group. Relevant blood glucose-related indices and cardiac function-associated indices of the two groups before and after treatment were analyzed and compared: The adverse reactions of the two groups were statistically analyzed, including hypotension, hypoglycemia, diarrhea and abdominal pain, anorexia, and nausea and vomiting. The patients were followed-up for six months, on which the major cardiovascular adverse events (MACE) and incidence of readmission for heart failure in the two groups were analyzed and compared. RESULTS:Treatment, the FBG, 2h PG and HbA1c levels in both groups dropped significantly (P<0.05), with significantly lower levels in the study group (P<0.05). After treatment, both groups showed significantly dropped NT-pro BNP, LVEDD and LVESD levels (P<0.05) and a significantly increased LVEF level (P<0.05), with more significant drops/increase in the study group (P<0.05). No significant difference was found between the two groups in the total incidence of adverse reactions (P=0.586). During the follow-up period, there was no significant difference in the incidence of MACE between the two groups (P>0.05), and the study group showed a significantly lower incidence of readmission for heart failure than the control group (P<0.05). CONCLUSIONS:Dapagliflozin can substantially improve the blood glucose and cardiac function of patients with both AMI and T2DM. It can lower the rate of readmission for heart failure, and provide various cardiovascular benefits besides hypoglycemic effect.

To probe the action of shikonin on cardiomyocyte damage triggered by high glucose and its possible mechanism. High glucose was used to induce rat cardiomyocyte H9C2 to establish a cell injury model, and different doses of shikonin were used to treat H9C2 cells. Flow cytometry tested cell apoptosis. The enzymelabeled method and water-soluble tetrazolium salt method were used to detect superoxide dismutase and malondialdehyde content, respectively. Quantitative reverse transcription polymerase chain reaction assayed circ_0000491 levels. After shikonin treatment, the apoptosis rate of H9C2 cells, levels of malondialdehyde in cells, and circ_0000491 contents were declined, and superoxide dismutase content was increased in a dosedependent manner. After transfection with si-circ_0000491, the apoptosis rate and malondialdehyde levels were suppressed, but superoxide dismutase content was increased in H9C2 cells. Transfection of plasmid cloning deoxyribonucleic acid-circ_0000491 could attenuate these inhibitory effects of shikonin on high glucose-induced H9C2 cell apoptosis and oxidative stress. Shikonin could inhibit cell apoptosis and oxidative stress by down-regulating circ_0000491, thereby improving high glucose-induced cardiomyocyte damage.

目的 研究三七皂苷(血塞通)对H9c2心肌细胞缺氧/复氧损伤的保护作用及机制.方法 将H9 c2心肌细胞随机分成5组:对照组、模型组、低剂量实验组、高剂量实验组和核因子E2相关因子2(Nrf2)抑制剂组.对照组细胞正常培养不做任何处理;模型组调整培养基,再进行缺氧/复氧处理;低剂量实验组、高剂量实验组和Nrf2抑制剂组:用0.30,0.60 mg·mL-1血塞通溶液和0.60 mg·mL-1血塞通溶液+2μmol·L-1 Nrf2抑制剂ML385预处理后,再进行缺氧/复氧处理.检测各组细胞存活率;用比色法测定乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平;用流式细胞仪检测细胞内活性氧(ROS)含量和细胞凋亡;用蛋白质印迹(Western blot)法检测细胞凋亡相关蛋白及Nrf2、血红素加氧酶-1(HO-1)蛋白表达水平.结果 对照组、模型组、低剂量实验组、高剂量实验组和Nrf2抑制剂组的细胞存活率分别为(100.00±1.23)％,(47.93±6.69)％,(63.11±5.90)％,(75.56±4.20)％和(48.27±4.63)％,凋亡率分别为(3.66±0.69)％,(69.10±4.26)％,(49.98±5.79)％,(26.44±5.78)％和(67.62±5.72)％;细胞上清LDH水平分别为(154.22±6.45),(255.47±9.37),(216.87±11.27),(185.98±14.18),(246.74±8.61)U·L-1;SOD活性分别为(34.80±3.81),(15.43±2.12),(20.83±1.11),(33.11±2.51),(21.65±2.44)U·mg-1;MDA含量分别为(1.29±0.20),(3.57±0.41),(3.19±0.22),(1.53±0.30),(3.32±0.18)nmol·mg-1;ROS相对荧光强度分别为1.07±0.17,3.88±0.61,3.16±0.31,1.65±0.26,3.19±0.28;模型组与对照组比较,高、低剂量实验组间,高、低剂量实验组与模型组比较,N rf2抑制剂组与高剂量实验组、对照组、模型组比较,差异均有统计学意义(均P<0.05).蛋白质印迹结果显示,缺氧复氧处理显著提升了H9c2细胞中cleaved-caspase 3和Bax表达水平,降低了Bcl-2表达(P<0.05).随着血塞通处理浓度的上调,cleaved-caspase 3和Bax的高表达被抑制,Bcl-2,Nrf2和HO-1的表达上调(P<0.05).加入Nrf2抑制剂后,血塞通对cleaved-caspase 3和Bax的表达抑制,Bcl-2和HO-1的表达增强功能均消失(P<0.05).结论 血塞通可能通过激活Nrf2/HO-1信号通路减轻缺氧/复氧诱导的H9 c2心肌细胞氧化损伤,发挥对心肌细胞损伤的保护作用.

目的:探讨S100A12在预测慢性心力衰竭(CHF)患者不良临床终点事件中的意义.方法:前瞻性收集2019年1月-2020年1月上海市静安区市北医院诊疗的CHF患者200例,通过18个月的随访发现,出现不良心脑血管事件(MACCE)的患者有63例,设为MACCE发生组;未出现MACCE事件的患者有137例,设为MACCE未发生组.比较两组患者的临床相关资料,分析S100A12水平与临床特征的相关性,并对S100A12高表达和低表达、BNP高表达和低表达的CHF患者进行生存分析,同时分析CHF患者发生MACCE的影响因素.结果:MACCE 发生组与 MACCE 未发生组中性别构成比、BMI、LVEDD、LVESD、EF、LVMI、SBP、DBP、TG、TC、LDL-C、HDL-C及NT-proBNP水平比较,差异无统计学意义(P＞0.05);MACCE发生组患者的BNP和S100A12水平明显高于MACCE未发生组,eGFR值明显低于MACCE未发生组,差异均有统计学意义(P＜0.05);S100A12 与年龄(r=0.217,P=0.005)和 BNP(r=0.317,P＜0.001)呈正相关性,与 eGFR(r=-0.214,P=0.013)呈负相关性;S100A12高表达组的生存期明显短于S100A12低表达组(x2=8.537,P＜0.001);BNP高表达组的生存期明显短于BNP低表达组(x2=5.194,P=0.005).年龄、BNP和S100A12是预测CHF患者MACCE的独立危险因素(P＜0.05),而eGFR是预测MACCE的保护因素(P＜0.05).结论:S100A12和BNP一样是预测MACCE的独立危险因素,并且随着S100A12的升高,CHF死亡率明显增加,说明S100A12对于预后判断可能具有明显价值.

目的 探索普萘洛尔对大鼠心脏细胞线粒体的影响.方法 普通大鼠用灌注技术分离心肌细胞,再用线粒体分离试剂盒从大鼠心肌细胞中分离线粒体.将线粒体悬液分为空白组和低、中、高剂量实验组,并分别给予0,2.5,5.0和10.0μg·mL-1普萘洛尔处理,加药后孵育30 min.用可见光比色法检测线粒体琥珀酸脱氢酶(SDH)活性和线粒体肿胀程度,用荧光比色法检测活性氧(ROS)产生量和线粒体跨膜电位(MMP).结果 中、高剂量实验组和空白组的SDH活性分别为(721.98±105.88),(339.17±48.98)和(1427.99±201.57)U·mg-1,ROS水平(2′,7′-二氯荧光素荧光强度)分别为2071.00±50.88,2210.25±131.63和969.99±22.96,MMP(JC-1荧光强度比值)分别为3.14±0.06,3.24±0.18和1.00±0.05,线粒体肿胀度(ΔA)分别为0.26±0.03,0.59±0.08和0.02±0.00.中、高剂量实验组的上述指标与空白组比较,差异均有统计学意义(均P<0.05).结论 普萘洛尔能提高ROS水平和破坏线粒体膜,导致心肌细胞凋亡,具有显著的心脏毒性.

目的:探讨紫杉醇通过上调HO-1表达,促进心肌细胞微管结构稳定预防缺血/再灌注(MI/R)损伤的机制.方法:将大鼠离体的灌注Langendorff心脏随机分为三组:对照组、缺血组、紫杉醇组,15 min的平衡期后,对照组进行120 min的常氧灌注;缺血组,缺血30 min后常氧再灌注120 min;紫杉醇组,缺血30 min后,在使用1μmol/L的紫杉醇常氧再灌注120 min;之后采用免疫组化方法和自由基检测试剂盒检测微管破坏情况,采用蛋白质印迹法研究潜在机制.结果:通过免疫组织化学分析微管形态,在对照组中可见微管结构完整,无明显断裂;在缺血组中可见微管连续中断,微管断裂;在紫杉醇组中可见微管结构基本完整,但微管稍有粗乱.蛋白质印迹分析显示紫杉醇组中JNK1的磷酸化水平显著增加.此外,HO-1的表达水平随着紫杉醇处理而增加,这可以被JNK的特异性抑制剂JNK-IN-8抑制.结论:紫杉醇在缺血时能维持微管结构稳定,通过心肌细胞JNK途径诱导HO-1表达或许是其中机制之一.

OBJECTIVE: To extract collagen protein from scales of fish,to prepare gel and to investigate in vitro diffusion rate of the drug in it.METHODS: The scales of fish were extracted effectively with pepsin and the collagen protein could be prepared after salting out,purification and freeze drying.Collagen protein gel was prepared using a serial mixture of citric acid solution,glycerol and ethanol and with salicylic acid as model drug.The in vitro diffusion rate of collagen protein gel was investigated by agar diffusion method using diffusion coefficient k as index,which was compared with the salicylic acid water-soluble ointment and greasy ointment.RESULTS: The content of collagen protein was 91.04%.The diffusion coefficient k of Salicylic acid collagen protein gel,salicylic acid water-soluble and greasy ointment were 68.11 mm2·h-1,58.04 mm2·h-1,17.67 mm2·h-1.CONCLUSION: Collagen gel can be used for external preparation to make drugs release faster.