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OBJECTIVE@#To explore the protective effect and possible mechanisms of bloodletting acupuncture at Jing-well points (BAJP) pre-treatment on acute hypobaric hypoxia (AHH)-induced myocardium injury rat.@*METHODS@#Seventy-five rats were randomly divided into 5 groups by a random number table: a control group (n=15), a model group (n=15), a BAJP group (n=15), a BAJP+3-methyladenine (3-MA) group (n=15), and a BANA (bloodletting at nonacupoint; tail bleeding, n=15) group. Except for the control group, the AHH rat model was established in the other groups, and the corresponding treatment methods were adopted. Enzyme-linked immunosorbent assay (ELISA) was used to detect creatine kinase isoenzyme MB (CK-MB) and cardiac troponins I (CTnI) levels in serum and superoxide dismutase (SOD) and malondialdehyde (MDA) levels in myocardial tissue. Hematoxylin-eosin (HE) staining was used to observe myocardial injury, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was used to observe cell apoptosis. Transmission electron microscopy detection was used to observe mitochondrial damage and autophagosomes in the myocardium. The mitochondrial membrane potential of the myocardium was analyzed with the fluorescent dye JC-1. Mitochondrial respiratory chain complex (complex I, III, and IV) activities and ATPase in the myocardium were detected by mitochondrial respiratory chain complex assay kits. Western blot analysis was used to detect the autophagy index and hypoxia inducible factor-1α (HIF-1α)/Bcl-2 and adenovirus E1B 19k Da-interacting protein 3 (BNIP3) signaling.@*RESULTS@#BAJP reduced myocardial injury and inhibited myocardial cell apoptosis in AHH rats. BAJP pretreatment decreased MDA levels and increased SOD levels in AHH rats (all P<0.01). Moreover, BAJP pretreatment increased the mitochondrial membrane potential (P<0.01), mitochondrial respiratory chain complex (complexes I, III, and IV) activities (P<0.01), and mitochondrial ATPase activity in AHH rats (P<0.05). The results from electron microscopy demonstrated that BAJP pretreatment improved mitochondrial swelling and increased the autophagosome number in the myocardium of AHH rats. In addition, BAJP pretreatment activated the HIF-1α/BNIP3 pathway and autophagy. Finally, the results of using 3-MA to inhibit autophagy in BAJP-treated AHH rats showed that suppression of autophagy attenuated the treatment effects of BAJP in AHH rats, further proving that autophagy constitutes a potential target for BAJP treatment of AHH.@*CONCLUSION@#BAJP is an effective treatment for AHH-induced myocardial injury, and the mechanism might involve increasing HIF-1α/BNIP3 signaling-mediated autophagy and decreasing oxidative stress.
Subject(s)
Animals , Rats , Acupuncture Therapy , Altitude , Apoptosis , Autophagy , Bloodletting , Hypoxia/metabolism , Membrane Proteins/pharmacology , Mitochondrial Proteins/pharmacology , Oxidative Stress , Rats, Sprague-DawleyABSTRACT
Transient,reversible myocardium injury can occur in patients with brain injury.Several pathophysiological mechanisms are involved in the development of such neurogenic myocardium injury.Excess catecholamine release plays a major role during myocardial injury.The clinical features include abnormal electrocardiographic,echocardiographic features and elevated biomarkers.In some patients stunned myocardium can be observed which may lead to hemodynamic instability or even cardiogenic shock.Inotropic agents and mechanical support are useful in improving cardiac function.β-adrenergic blockade is likely to attenuate the catecholamine toxicity but its use remains controversial.
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Objective:To explore the effect of salvianolic acid B (Sal-B) on the myocardial apoptosis in rats with sepsis. Method:The 50 male SD rats were randomly divided into sham operation group, model group (cecal ligation and perforation were performed to replicate the animal model of sepsis)and Sal-B low, medium and high-dose group(6, 12, 24 mg·kg-1).The myocardial necrosis markers troponin T(TnT), cardiac troponin I (cTnI), creatine kinase-MB (CK-MB) and the tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) were assayed by enzyme-linked immunosorbent assay(ELISA).The antioxidant enzyme superoxide dismutase (SOD) activities and malonaldialdehyde (MDA) levels in myocardial homogenates were determined by spectrophotometrically. Haematoxylin-eosin (HE) staining was used to evaluate the pathological change in rats. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) was used to detect apoptosis of myocardial cells in hearts, respectively. Western blot was used to detect the expression levels of apoptosis-related protein cysteine protease-3 (Caspase-3), b-lymphocytoma-2 (Bcl-2), Bcl-2-related X protein (Bax), autophagy microtubule-related light chain 3 (LC3) and Beclin-1 in myocardial tissue. Result:Compared with sham group, the levels of TnT, CK-MB and cTnI in model group were significantly increased (Pα, IL-1β and IL-6 in myocardial tissue were significantly increased (PPPPPPPα, IL-1 and IL-6 in the myocardial tissue were significantly decreased (PPPPPPPPPPConclusion:Sal-B showed a protective effect on the myocardial apoptosis in septic rats maybe by depressing inflammatory infiltration, anti-oxidative effects and improving the exceptional expression of the proteins such as Bax, Bcl-2, Caspases-3 by enhancing the level of autophagy.
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Objective To explore the effect of Shuxuening on early myocardial injury markers and oxidative stress in severe sepsis patients with myocardial injury. Methods A total of 102 severe sepsis patients with myocardial injury, who received therapy in our hospital from Mar. 2013 to Jun. 2016, were randomly divided into two groups; control group (51 cases) and therapy group (51 cases). The patients in the control group received routine treatments and the therapy group were given Shuxuening based on routine treatment. We detected the levels of plasma N-terminal pio-brain natriuretic peptide (NT-proBNP), heart-type fatty acid binding protein (hFABP), cardiac troponin I (cTnl), malondialdehyde (MDA), superoxicle dismutase (SOD) and gluiaihione peroxidase (GSH-Px) of patients before treatment (at admission), after treatment for 6 h and 72 h (after admission), and analyzed the change of left ventricular ejection fraction (LVEF), acute physiology, chronic health evaluation (APACHE) || score, length of ICU slay and 28-day mortality of the patients. Results At admission, there was no difference in the levels of plasma NT-proBNP, hFABP, cTnl. MDA. SOD. GSH-Px, APACHE || score or LVEF between the two groups (P>0.05). After treatment for 6 h, the levels of plasma NT-proBNP, hFABP, cTnl and MDA in the therapy group were significantly lower and the activities of plasma SOD and GSH-Px were significantly higher than those in the control group (P0. 05). APACHE II scores after treatment were significantly lower than that before treatment in the two groups (P0. 05). The therapy group had a significantly lower 28-day mortality than the control group (0. 05). The therapy group had a significantly lower mortality than the control group (P<0. 05). Conclusion Therapeutic effect of Shuxuening on the severe sepsis patients with myocardial injury is superior to the routine treatment. Shuxuening can decrease the levels of NT-proBNP. hFABP. cTnl, and MDA and APACHE || score, and can increase the activities of SOD and GSH-Px.
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AIM To investigate the effects of safflower yellow on myocardial injury in patients with severe sepsis.METHODS Using prospective research methods,ninety-two patients with severe sepsis treated in our hospital from Jan.2013 to Mar.2016 were divided equally into two groups:control group (routine treatment) and observation group (routine treatment + safflower yellow).In addition,6 and 72 hours after the treatment,heart-type fatty acid binding protein (H-FABP),creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) of patients were detected,and the changes of left ventricular ejection fraction (LVEF) and sequential organ failure assessment (SOFA) scores were observed;length of ICU stay,cumulative incidence of major adverse cardiac events (MACE) and 28-day survival also were recorded at the same time.RESULTS In admission,there were no differences in the levels of H-FABP,CK,CK-MB and LVEF,SOFA scores between the two groups.After 6 hours treatment,the levels of H-FABP,CK,CK-MB and SOFA score in the observation group were lower than those in the control group;the two groups had higher levels of H-FABP,CK and CK-MB than those before the treatment,SOFA score was lower than that before the treatment;After 72 hours treatment,H-FABP,CK,CK-MB and SOFA score were lower than those after 6 hours treatment;SOFA score in the observation group was lower than that in the control group;there were no differences in H-FABP,CK and CK-MB between the two groups.The observation group had a lower cumulative incidence of MACE than the control group.There was no statistical difference in LVEF and length of ICU stay after the treatment between the two groups.The observation group had a higher 28-day survival than the control group,the difference was statistically significant (76.08％,35/46 vs 54.35％,25/46;x2 =4.529,P =0.033).The level of serum H-FABP in severe sepsis patients was negatively correlated with LVEF (r =-0.270,P =0.009).CONCLUSION Therapeutic effects of safflower yellow on myocardial injury in patients with severe sepsis is superior to routine treatment with the improvement of the prognosis of patients to a certain extent.
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Objective To investigate the clinical value of heart-type fatty acid-binding protein ( H-FABP) and N terminal probrain natriuretic peptide (NT-proBNP) in sepsis patients with myocardium injury. Methods 118 sepsis patients were included as survivor group (68 cases) and death group (50 cases) according to their prognosis outcome. 50 healthy people were selected as control group. Creatase, H-FABP, NT-proBNP, APACHEⅡscore and 28 day morbidity of control group and sepsis patients were assessed at 1 h, 6 h after admission by physical examination . Results At 1 h after admission , APACHEⅡscore , H-FABP and NT-proBNP level in sepsis patients were significantly higher than control group (P < 0.05); APACHEⅡscore, H-FABP, NT-proBNP and cTnI level at 6 h after admission were higher than that at 1 h (P < 0.05); APACHEⅡscore, H-FABP and NT-proBNP level in death group were higher than survivor group at 1, 6 h after admission (P < 0.05), cTnI level at 6 h after admission was higher in death group (P < 0.05). Futhermore, H-FABP, NT-proBNP and cTnI at 6 h after admission were positively correlated with each other (both P < 0.05). At 6 h after admission , H-FABP showed a better predictive value of 28-day mortality than NT-proBNP and APACHEⅡscore (P < 0.05). Conclusion H-FABP and NT-proBNP may suggest important significance in early diagnosis and prognosis prediction of sepsis patients with myocardium injury.
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Objective To explore the value of cardiac troponin Ⅰ (cTnI),brain natriuretic peptide (BNP),blood lactate and acute physiology and chronic health evaluation (APACHE) Ⅱ score which used to evaluate the severity of sepsis shock patients with myocardium injury.Methods Data of 61 patients with sepsis shock were collected,and cTnI,BNP,blood lactate were monitored and APACHE Ⅱ score were scored at admission,6,24 h after treatment.All of these indicators were compared between death group and survival group.Results In 61 patients,35 cases of them were lived (survival group),26 cases of them were died (death group).The cTnI,BNP,blood lactate and APACHE Ⅱ score at admission in death group was significantly higher than that in survival group (P＜ 0.05).In death group all of these indicators there was no significantly difference between admission and 6 h after treatment (P ＞0.05);24 h after treatment was significantly higher than that 6 h after treatment (P ＜ 0.05).In survival group 6,24 h after treatment was significantly lower than that at admission,24 h after treatment was significantly lower than that 6 h after treatment [BNP:(478.1 ± 95.3)ng/L vs.(1 025.2 ± 263.3) ng/L,cTnI:(0.9 ± 0.1) μ g/L vs.(2.5 ± 0.4) μ g/L,blood lactate:(2.4 ± 0.3) mmol/L vs.(5.4 ± 2.1) mmol/L,APACHE Ⅱ score:(11.4 ± 1.8) scores vs.(15.6 ± 2.9) scores] (P ＜ 0.05).Conclusion BNP,cTnI,blood lactate and APACHE Ⅱ score may be used to evaluate the severity of sepsis shock patients with myocardium injury and predict outcome of the patients.
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Objective To observe the protective and antioxidative effect of Xinjihuoliyin on the myocardium injury induced by adriamycin (ADM) in rats. Methods 80 SD rats were randomly divided into four groups:normal group, control group, Xinjihuoliyin group and positive control group (Huangqishengmaiyin group). In control group, Xinjihuoliyin group and Huangqishengmaiyin group, ADM was intraperitonial injected at a dose of 2.5 mg/kg, three times every week, for 4 weeks, while normal saline was intraperitonial injected at a dose of 3 mL/kg in normal group. In Xinjihuoliyin group, Xinjihuoliyin was intragastric administrated once a day at a dose of 10 g/kg. In Huangqishengmaiyin group, Huangqishengmaiyin was intragastric administrated once a day at a dose of 7 mL/kg and distilled water was given to other two groups. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) of serum and myocardium were assayed. The myocardial pathomorphism was detected at the same time. Results Compared with the control group, MDA of serum and myocardium was lower, and SOD of serum and myocardium was higher in Xinjihuoliyin and Huangqishengmaiyin group. The scale of myocardial pathological damage in Xinjihuoliyin and Huangqishengmaiyin group was improved. Conclusion Xinjihuoliyin has protective effect and antioxidative effect on the myocardium injury induced by adriamycin in rats.
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Aim To study the effects and mechanism of Guanxinkang capsules on myocardial injury induced by isoproterenol in rats.Methods 30 male Wistar rats were randomly divided into 3 groups:control group,acute myocardial ischemia group and Guanxinkang capsules group.Rats were given injections of ISO subcutaneously.Electrocardiography were performed,serum and myocardium creatine kinase(CK),creatine kinase MBmass(CK-MB),lactate dehydrogenase(LDH) and nitric oxide(NO) were detected,and the levels of NO and endothelins(ET) in myocardium were measured as well.Results The rising degree of ST-T obviously decreased in Guanxinkang capsules group,and the levels of serum CK,CK-MB and LDH decreased in Guanxinkang capsules group,compared with those of acute myocardial ischemia group(P
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Objective To study the effects and mechanisms of myocardial injury in schistosome-infected mice.To investigate the effects and mechanisms of quercetin on myocardial injury due to the development of hepatic fibrosis after being treated by Praziquantel.Methods Eighty mice were divided into four groups:group A,group B,group C,and group D.Group A,group B,and group C were infected with Schistosoma japonicum cercariae.After 8 weeks,group A was treated with Praziquantel 500 mg/kg for 2 d,group B was treated with quercetin 30 mg/(kg?d) for 8 weeks after being treated with Praziquantel 500 mg/kg for 2 d.Group C was taken as experimental control without any treatment.Group D was taken as normal control.At the week 16,all mice were sacrificed and a part of liver tissue and myocardium tissue were preserved.HE Staining,electric microscope,RT-PCR,and immunohistochemical technique were applied to observing the changes of hepatic and cardiac histopathology,myocardial ultramicrostructure,the expression of myocardial c-fos,c-jun mRNA,and the contents of myocardial transforming growth factor-?1 (TGF-?1),typeⅠand typeⅢcollagen in mice infected with S.japonicum before and after treatments. Results There was different degree of myocardial injury among three groups of experimental control, Praziquantel treatment,Praziquantel combined with quercetin treatment.Praziquantel treatment relieved the degree of hepatic fibrosis and myocardial injury.The content of myocardial c-fos mRNA,c-jun mRNA,TGF-?1,typeⅠand typeⅢcollagen were obviously reduced compared to the experimental control. When Praziquantel treatment combined with quercetin,the degree of hepatic fibrosis and myocardial injury were further relieved.Although the content of myocardial c-fos mRNA,c-jun mRNA,TGF-?1, typeⅠand thypeⅢcollagen were still higher than those in normal control,those were reduced significantly compared to the group treated with Praziquantel.Conclusion Hepatic cirrhosis due to advanced schistosomiasis may lead to cardiac remodeling by stimulating the expression of immediate early gene and promoting the overexpression of TGF-?in myocardium.Anti-fibrosis therapy can reduce the degree of cardiac remodeling.Quercetin may protect myocardium through reducing the degree of hepatic fibrosis and inhibiting the expression of immediate early gene,which could decrease the level of myocardial TGF-?1.
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Objective:To detect TNF-? in the tissue of myocardium injury during stress and discuss its significance.Methods:To establish a model of myocardium lesion by injecting ISO to mice abdominal cavity,then TNF-? in the tissue of heart was assessed by immunohistochemical method of SP and HE staining in paraffin sections.Results:There were little positive substance of TNF-? expressed in heart in normal control.The positive substance of TNF-? increased significantly after stress.Conclusion:Increase in the expression of TNF-? in stress indicate its participation in the process of myocardium injury,and it may be an objective marker for evaluation of myocardium injury.