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Objective:To analyze and explore the independent risk factors of 28-day mortality in patients with septic myocardial injury.Methods:A retrospective cohort study was conducted to collect clinical data of 505 patients diagnosed with sepsis related myocardial injury admitted to the intensive care unit (ICU) of the Affiliated Hospital of Jining Medical University from January 2015 to December 2020. According to the 28-day survival status of patients, they were divided into survival group and death group. COX multivariate regression analysis was used to analyze the influencing factors of the 28-day mortality rate of sepsis related myocardial injury patients, and receiver operating characteristic (ROC) curves were drawn to evaluate the effectiveness of independent risk factors in predicting the 28-day mortality rate of sepsis related myocardial injury patients.Results:A total of 505 patients with sepsis myocardial injury were included, of which 282 survived on 28 days and 223 died, with a mortality rate of 44.16%. COX multivariate regression analysis showed that Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, blood lactate (LAC), oxygenation index (PaO 2/FiO 2), admission heart rate, and albumin were independent risk factors for sepsis associated myocardial injury mortality at 28 days (all P<0.05). ROC curve analysis showed that the area under the ROC curve (AUC) of SOFA score was 0.766 2, and the 95% confidence interval (95% CI) was 0.724 5-0.807 9; The predictive value of 28-day mortality in sepsis associated myocardial injury patients was superior to APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin [The AUC values were 0.754 1(0.711 5-0.796 7), 0.752 6(0.710 1-0.795 1), 0.697 0(0.649 7-0.744 2), 0.623 2(0.573 7-0.672 7), and 0.620 3(0.570 8-0.669 7), respectively]. Conclusions:SOFA score, APACHE Ⅱ score, LAC, PaO 2/FiO 2, admission heart rate, and albumin are independent risk factors for the 28-day mortality rate of sepsis related myocardial injury. Clinical practice should identify these factors early, intervene early, and improve patient prognosis.
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Objective:To investigate the effect of Astragaloside Ⅳ on high glucose-induced cardiomyocyte pyroptosis.Methods:H9c2 cells were cultured in vitro and divided into control group(5.5 mmol/L glucose), high glucose group(33.3 mmol/L glucose), Astragaloside Ⅳ group(33.3 mmol/L glucose+ 100μmol/L Astragaloside Ⅳ), and NLRP3 inhibitor group(33.3 mmol/L glucose+ 1μmol/L MCC950). Cell counting kit 8(CCK-8)was used to detect the activity of H9c2 cells.Lactate dehydrogenase(LDH)kit was used to detect the content of LDH in cell supernatant.Superoxide anion fluorescent probe(DHE)was used to detect the level of intracellular reactive oxygen species(ROS). Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression levels of pyroptosis-related genes.Immunofluorescence was used to detect the fluorescence intensity of NLRP3.Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of inflammatory factors in cell supernatant.Results:When the concentration of Astragaloside Ⅳ was 100 μmol/L, it could significantly inhibit the decrease of cardiomyocyte viability induced by high glucose( P<0.01)and reduce LDH release( P<0.01). Compared with the control group, the level of ROS was increased( P<0.01), the mRNA and protein expressions of pyroptosis-related molecules were up-regulated( P<0.01 for all), the fluorescence intensity of NLRP3 was increased( P<0.01), and the levels of inflammatory factors in the cell supernatant were increased in the high glucose group( P<0.01). Compared with the high glucose group, the ROS level was decreased( P<0.01), the mRNA and protein expressions of pyroptosis-related molecules were down-regulated( P<0.05 or P<0.01), the fluorescence intensity of NLRP3 was decreased( P<0.01), and the levels of inflammatory factors in cell supernatant were decreased( P<0.05 or P<0.01)in Astragaloside Ⅳ group and inhibitor group. Conclusions:Astragaloside Ⅳ plays a protective role in high glucose-induced cardiomyocyte injury by inhibiting NLRP3/Caspase-1 signaling pathway and inhibiting pyroptosis.Moreover, it can improve the anti-inflammatory and antioxidant properties in cell models.
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Objective:To investigate the protective effects and related mechanisms of Astragaloside Ⅳ(ASⅣ)alleviating Angiotensin II-induced cardiomyocyte hypertrophy.Methods:H9c2 cardiomyocytes were divided into six groups: normal control group, ASⅣ group(ASⅣ 100 μmol/L), AngⅡ group(AngⅡ 1 μmol/L), and three ASⅣ dose experiments(AngⅡ 1 μmol/L + ASⅣ 25 μmol/l group, AngⅡ 1 μmol/L+ ASⅣ 50 μmol/l group, AngⅡ1 μmol/L+ ASⅣ 100 μmol/L group), and simultaneously cultured for 24 hours.Cardiomyocyte viability was assessed by CCK8 assay, and surface area of culturedcardiomyocytes in each group was assessed by immunofluorescence assay.Atrial natriuretic peptide(ANP)mRNA expression was assessed by fluorescence real-time quantitative RT-PCR.And LC3 protein expression, an autophagy related protein, was assessed by Western blotting as well as immunofluorescence.Results:(1)AngⅡ decreased cardiomyocyte H9c2 viability in a dose-dependent manner( P<0.05). ASⅣ could inhibit the decrease of cardiomyocyte H9c2 viability in response to AngⅡ in a dose-dependent manner( P<0.05). (2)H9c2 cardiomyocytes induced by AngⅡ showed a significantly larger cell area and significantly higher ANP mRNA and ANP protein expression compared with controls.Different concentrations of ASⅣ intervention could reverse the increase of cardiomyocyte H9c2 area induced by AngⅡ and also decreased the expression of ANP protein induced by AngⅡ in a dose-dependent manner(all P<0.05). (3)Compared with the control group, the autophagy level and the expression of autophagy marker LC3II/I of H9c2 cardiomyocytes induced by AngⅡ were significantly increased(all P<0.05). ASⅣ could inhibit AngⅡ-activated autophagy, and the difference was statistically significant( P<0.05). ASⅣ inhibited the expression of LC3II/I in H9c2 cardiomyocytes stimulated by AngⅡ, and the difference was statistically significant( P<0.05). Conclusions:ASⅣ inhibits AngⅡ-induced cardiac hypertrophy by inhibiting autophagy of cardiomyocytes.
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Objective:To investigate the effect of Astragaloside Ⅳ on abdominal aorta constriction-induced cardiac hypertrophy by activating the nuclear factor E2-related factor 2/heme oxygenase-1(Nrf2/ HO-1)signaling pathway, so as to improve cardiac function.Methods:From Sep.2017 to Jan.2019, 40 male SD rats were selected and abdominal aortic constriction(AAC)was used to establish a rat model of chronic heart failure.Rats were divided into three ACC groups: the model group, the benazepril HCl group and the Astragaloside Ⅳ group, plus the sham operation group.Rats in the benazepril HCl and Astragaloside Ⅳ groups were given 10 mg·kg -1·d -1 benazepril HCl and 50mg·kg -1·d -1 Astragaloside Ⅳ respectively by gavage, and the sham operation group and the model group were given normal saline of the same volume by gavage.After 8 weeks of treatment, cardiac structure and functional parameters were examined using cardiac color doppler ultrasound, while hemodynamics and morphological changes of myocardial cells were detected by immunofluorescence, serum brain natriuretic peptide(BNP)levels were detected by an enzyme-linked immunosorbent assay(ELISA), and Nrf2 and HO-1 mRNA expression in myocardial tissues were detected by reverse transcription-quantitative real-time PCR(RT-qPCR). Results:Compared with the sham operation group, the ratio of heart weight to femoral neck length(495.47±12.38), the ratio of heart weight to body weight(6.44±0.18), left ventricular end-diastolic diameter(LVEDD)(4.72±0.04 mm), left ventricular posterior wall thickness(LVPWT)(1.87±0.03)mm and the BNP level(151.61±5.67)mmol/L all increased( P<0.05), but the expression of mRNA Nrf2(0.36±0.02)and HO-1(0.27±0.02)decreased( P<0.01)in the model group.Compared with the model group, the ratio of heart weight to femoral neck length(261.88±12.97 and 286.40±12.56), the ratio of heart weight to body weight(3.38±0.13 and 3.71±0.15), left ventricular end-diastolic diameter(5.84±0.05)mm and (6.01±0.10)mm, left ventricular posterior wall thickness[(1.57±0.03)mm and(1.64±0.03)mm]and the BNP level[(99.40±4.97)mmol/L and(120.66±5.80)mmol/L]all decreased( P<0.05), but the mRNA expression of Nrf2(1.06±0.01 and 1.04±0.01)and HO-1(1.08±0.06 and 0.95±0.02)increased in the benazepril HCl and Astragaloside Ⅳ groups, respectively( P<0.01). Conclusions:Astragaloside Ⅳ has an effect of anti-oxidative stress, can inhibit heart failure and improve cardiac function, and its mechanisms may be related to the Nrf2/ HO-1 signaling pathway.
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Stress cardiomyopathy (SCM) is a kind of clinical syndrome characterized by transient ventricular enlargement and left ventricular regional systolic dysfunction caused by strong mental stimulation or physical stress, and accompanied by electrocardiogram (ECG) changes. Its clinical symptoms and ECG manifestations are similar to those of acute coronary syndrome in the early stage of onset, which is easy to be misdiagnosed. However, patients in intensive care unit (ICU) are often in critical and severe condition, and they often preceded different degrees by emotional or physical stress. Therefore, patients in ICU are prone to complicated with SCM. Otherwise, the symptoms of SCM patients in ICU are not typical. Early diagnosis and optimal treatment are the key to improve the prognosis of patients in ICU. The etiology, epidemiology, pathophysiological mechanism, diagnosis and management of SCM in ICU are reviewed in this paper.
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Objective To analyze changes in serum levels of inflammatory factors,galectin-3 (Gal-3),fractalkine(FKN) and interleukin-6 (IL-6),in patients with dilated cardiomyopathy (DCM) or ischemic cardiomyopathy (ICM),and to explore their clinical significance.Methods Seventy-six hospitalized patients with DCM were selected to serve as a DCM group,and 78 patients with ischemic cardiomyopathy were selected into an ICM group from October 2016 to December 2017 at the Department of Cardiology,and patients in the two groups received cardiac function classification.Meanwhile,82 healthy people were included as a control group.Fasting venous blood was collected,and serum levels of Gal-3,FKN,IL-6,and BNP were measured.The correlations of Gal-3,FKN,and IL-6 with DCM or ICM were analyzed.Results Levels of plasma BNP and serum Gal-3,FKN,and IL-6 in the DCM and ICM groups were higher than those in the control group,and their levels in the DCM group were significantly higher than in the ICM group.Levels of plasma BNP and serum Gal-3,FKN,and IL-6 increased as their New York Heart Association(NYHA)classification went higher in both the DCM and ICM groups.For patients classified at the same level,serum levels of Gal-3,FKN,and IL-6 of the DCM group were significantly higher than those of the ICM group(P ＜ 0.05).BNP levels showed no difference between the two groups(P ＞0.05).Spearman correlation analysis indicated positive correlations of NYHA classification with levels of BNP(r =0.30,0.19),Gal-3(r=0.24,0.19),FKN(r =0.63,0.51),and IL-6(r =0.28,0.15)in both the DCM and ICM groups(P ＜ 0.05),and the correlation was stronger in the DCM group.Conclusions Increased expression of plasma BNP,Gal-3,FKN,and IL-6 in patients with DCM and ICM are closely related to the severity of cardiac function impairment.Monitoring changes in levels of plasma BNP and serum inflammatory factors Gal-3,FKN and IL-6 provides important clues for the differential diagnosis between DCM and ICM,the assessment of clinical conditions and treatment-related decisions.
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Objective: To study the impact of astragaloside on ventricular remodeling and peroxisome proliferator activated receptor a (PPARa) expression in pressure-overload rats and to preliminarily explore its mechanism. Methods: Pressure-overload rat's model was established by abdominal aorta constriction (AAC) in 8-week old SD rats and the result was conifrmed by echocardiography at 6 weeks later. Pressure-overload rats were divided into 4 groups with different intragastric treatment: Model control (normal saline) group, Benazepril hydrochloride [10mg/(kg.d)] group, Low-dose astragaloside [40mg/(kg·d)] group and High-dose astragaloside [80mg/(kg.d)] group; in addition, Sham operation group, the rats received intragastricnormal normal saline.n=20 in each group and all animals were treated for 8 weeks. Rat's cardiac structure and function indexes were assessed by echocardiography, hemodynamic parameter was examined by left ventricular intubation, myocardium and blood levels of free fatty acid (FFA) were determined, morphological changes of myocardial tissue was observed by HE and Masson staining, mRNA and protein expressions of PPARa were measured by qRT-PCR and Western blot analysis. Results: Compared with Sham operation group, Model control group showed increased left ventricular mass index(LVMI), collagen volume fraction (CVF) and FFA level, allP<0.05, while decreased mRNA and protein expressions of PPARa, bothP<0.05. Compared with Model control group, Low-dose and High-dose astragaloside groups presented reduced LVMI, CVF and FFA level, allP<0.05-0.01, while elevated mRNA and protein expressions of PPARa, bothP<0.01. Conclusion:Astragaloside IV mayinhibit myocardial remodeling in pressure-overload rats, which might be via up-regulating mRNA and protein expressions of PPARa, enhance myocardiumFFA utilization, and therefore improve myocardial energy metabolism.
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AIM:To observe the effects of astragaloside IV (AS-IV) on myocardial fibrosis in chronic heart failure ( CHF) rats and to explore the underlying mechanism preliminarily .METHODS:Chronic heart failure model rats established by abdominal aorta constriction (AAC) were divided into CHF group, valsartan group and AS-IV group.Sham operation group was also established .The rats in valsartan group and AS-IV group received valsartan and AS-IV at 2 and 30 mg· kg-1 · d-1 , respectively.The rats in sham operation group and CHF group received normal saline .After 8 weeks of treatment, the cardiac structure and the hemodynamic parameters were measured .The morphologic changes of myocardial tissue were observed after staining .The expression of long-chain acyl-CoA dehydrogenase ( LCAD) and 6-phosphofructoki-nase-1 (PFK1) at mRNA and protein levels was determined by RT-qPCR and Western blot.RESULTS:Compared with sham operation group , left ventricular mass index ( LVMI) , collagen volume fraction ( CVF) , left ventricular posterior wall depth (LVPWD), and the mRNA and protein of PFK1 in CHF group were increased (P<0.05), while the mRNA and protein levels of LCAD were decreased (P<0.05).Compared with CHF group, the LVMI, CVF, LVPWD, and the mRNA and protein levels of PFK1 in valsartan group and AS-IV group were decreased (P<0.05), while the mRNA and protein levels of LCAD were increased (P<0.05).CONCLUSION:AS-IV inhibits myocardial fibrosis in the CHF rats , the mechanism of which might be associated with up-regulating the expression of LCAD , down-regulating the expression of PFK1 and normalizing the myocardial energy metabolism .
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Objectives To explore the clinical effect of coupling meglumine cyclic adenylate (MCA)and the human granulocyte colony-ostimulating factor (G-CSF)on rat with diastolic heart failure(DHF).Methods Totally 60 rats of DHF model were evenly divided into 4 groups according to random number:Control group(n=15,control),Model group(n=15,DHF model),MCA group(n =15,treated with MCA)and MCA+GCSF group(n=15,treated with MCA plus G-CSF).MCA group were administered by intragastric injection of MCA 30 mg/kg/d for 15 d,MCA+G-CSF group were administered by intragastric injection of MCA 30 mg/kg/d and plus G-CSF 100 μg/kg/d for 15 d,while Control group and Model group were given same volume of saline solution.BIOPAC SYSTEM was used to analyze the model establishment.The mRNA levels of GATA-4 and Cx43 were measured by RT-PCR.The protein expressions of GATA-4,Cx43,cTNI and c-kit were measured with western blotting.ELISA and flow cytometry were used to detect cAMP and differentiation rate of bone marrow mesenchymal stem cells (BMSCs),respectively.Results Compared with MCA group,the denaturation degree of myocardial tissues in DHF rat was significantly improved than in MCA+G-CSF group.Moreover,the level of GATA-4 (1.62 ± 0.09),Cx43 (1.02 ± 0.07),cTNI (1.42 ± 0.12),c-kit (0.65±0.02),cAMP(283.67± 18.09)nmol/L and BMSCs cell differentiation rate(38.62 ± 1.52)％ in MCA + GCSF group were significantly promoted (all P＜ 0.05)than in MCA group,GATA-4 (0.82±0.07),Cx43 (0.52±0.05),cTNI(0.86 ± 0.13),c-kit (0.48 ± 0.03),cAMP(198.83 ± 16.03) nmol/L and BMSCs cell differentiation rate (19.82 ± 0.89)％.Conclusions The combination of MCA with G-CSF is significantly improved DHF than single MAC treatment,which may regulate BMSCs differentiation though cAMP/PKA signaling pathways.
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Objective: To observe the effects of astragaloside IV on myocardial fibrosis and connective tissue growth factor (CTGF) expression in experimental rats with chronic heart failure (CHF). Methods: CHF model was established by abdominal aorta constriction (AAC) and the rats were divided into 5 groups:Sham operation group, the rats received normal saline 2 ml/day, n=10, CHF group, the rats received normal saline 2 ml/day, n=12;Astragaloside IV groups, CHF rats received astragaloside IV at (20, 40, 60) mg/kg respectively and n=12 in each group. All animals were treated for 4 weeks. Hemodynamic indexes were monitored, left ventricular mass index (LVMI) was calculated, morphologic changes of myocardial tissue was observed by HE staining, myocardial ifbrosis degree and collagen volume fraction (CVF) were measured by Masson staining. The mRNA and protein expressions of CTGF were detected by RT-PCR and immunohistochemistry, Western-blot analysis respectivety. Results: Compared with CHF group, 3 Astragaloside IV groups had decreased LVMI and CVF, P Conclusion: Astragaloside IV can inhibit myocardial ifbrosis and improve cardiac function in CHF rats, which might be via inhibiting the over expression of myocardial CTGF.
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Objective To investigate the relationship between the plasma levels of ET-1,TAT,and hs-CRP and slow coronary flow syndrome (SCFS),and explore effects of coronary endothelial function,coagulation function,and inflammatory reaction on blood flow of coronary artery.Methods A total of 400 cases with normal blood flow of coronary artery by coronary angiogram was randomly selected.The coronary flow patterns were determined by corrected thrombolysis in myocardial infarction frame count method (cT-FC).Among them,45 cases whose average cTFC more than 27 were assigned as SCFS group,the other 45 cases no SCFS.Plasma levels of ET-1,TAT and hs-CRPwere examined with enzyme-linked immunosorbent assay (ELISA),and were compared between two groups.Moreover,multivariate analysis evaluating predictors of SCFS was performed with regression test.Results No statistical difference was found between two groups concerning the gender,history of hypertension,diabetes mellitus,and cigarette alcohol percentage..The plasma level of HDL in SCFS group was lower than that of no SCFS [(1.22 ± 0.42) mmol/L vs (1.44±0.34) mmol/L,t =-2.731,P ＜0.01],but the plasma level of glucose in the former was higher than that of the latter [(5.68 ±0.62) mmol/L vs (5.10 ±0.84) mmol/L,t =3.727,P ＜0.01].However,Plasma levels of ET-1,TAT and hs-CRP in SCFS were higher than that of no SCFS [(94.3 ± 16.78) ng/Lvs (83.5±12.53) ng/L,t =3.051,P ＜0.01;(12.96±3.24)μg/Lvs (8.76 ±2.64)μg/L,t =5.945,P ＜ 0.01 ; (2.48 ± 0.35) μg/L vs (1.38 ± 0.46) μg/L,t =11.259,P ＜ 0.01].Furthermore,Logistic regression analysis showed that ET-1,TAT and hs-CRP were risk factors for SCFS (OR ＞ 1.22).Conclusions Due to coronary endothelial dysfunction,endothelial inflammatory reaction,and activated coagulation function,slow coronary flow of coronary artery occurs.
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Ventricular myocytes from hearts of the neonatal SD rats were treated with 10-7,10-6,and 10-5 mol/L simvastatin for 72 hours under high glucose condition. Compared with control group,the viability of cadiomyocyte was significantly lower in high glucose group (P＜0.01 ).The activity of lactate dehydrogenase,the relative expressions of NADPH oxidase subunits p22phox,p47phox mRNA,and reactive oxygen species level in the high glucose group were higher than those of control group ( all P＜0.05).lndexes mentioned above were significantly improved by simvastatin treatment in a dose-dependent manner.These results suggest that simvastatin ameliorates high glucose-induced injury of cardiomyocytes via increasing the expression of NADPH oxidase mRNA.