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Aim To investigate the effeets of liraglutide ( LRG) on myocardial injury in type 2 diabetes melli- tus (T2DM) rats and its mechanisms.Methods For¬ty male SD rats were alloeated into eontrol group, T2DM group, LRG group, and LRG + AMPK inhibitor Compound C group (LRG + CC ).Four weeks later blood glucose and blood lipids of T2DM rats were measured.The eardiae function was measured by echo¬cardiography.The activities of superoxide dismutase (SOD ) , glutathione ( GSH ) and the malondialdehyde (MDA) eontent were assessed with corresponding rea¬gent kits.Cardiomyoeyte apoptosis was analyzed by TXJNEL staining.The expressions of inflammation, oxi-dative stress, apoptosis, autophagy, and AMPK/ mTOR signaling related proteins were deteeted by Western blot.Results Treatment with LRG alleviated hyperglycemia and hyperlipidemia, and improved heart function markers in T2DM rats.LRG inhibited inflam¬mation, oxidative stress and apoptosis and restored au- tophagy in T2DM rats by decreasing the expression of IL-6, TNF-a, IL-lp, N0X2, N0X4, cleaved caspase-3, Bax, p-mTOR/mTOR and the MDA con¬tent , and increasing the expression of Bcl-2, Atg5, Beclin-1 , LC3-II/LC3-I, p-AMPK/AMPK and the ac¬tivities of SOD and GSH.However, these effects were largely abolished by the AMPK inhibitor Compound C.Conclusions LRG exerts a protective role against dia¬betes-induced myocardial injury by ameliorating in-flammation, oxidative stress and apoptosis via the AMPK/mTOR autophagy signaling.
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Objective To evaluate the role of calcineurin ( CaN)/nuclear factor of activated T cell cytoplasmic 4 protein ( NFATc4) signaling pathway in inflammatory responses in lung tissues of rats with ventilator-induced lung injury ( VILI) . Methods Twenty-four clean-grade healthy male Wistar rats, aged 5-8 weeks, weighing 220-250 g, were divided into 3 groups ( n=8 each) using a random number table method: control C (group C), VILI group and cyclosporine A plus VILI group (group CsA+VILI). The animals were anesthetized with pentobarbital and tracheostomized. The rats were mechanically ventilated for 6 h with the tidal volume set at 40 ml/kg and respiratory rate at 40 breaths/min to establish the model of VI-LI. The rats kept spontaneous breathing in group C. CaN specific inhibitor cyclosporine A 10 mg/kg was in-traperitoneally injected at 1 h before ventilation in group CsA+VILI. Rats were sacrificed immediately after ventilation, lung tissues were obtained and stained with hematoxylin and eosin to evaluate lung injury, broncho-alveolar lavage fluid was collected for determination of tumor necrosis factor-alpha ( TNF-α) , inter-leukin-1beta ( IL-1β) and IL-6 concentrations by enzyme-linked immunosorbent assay, and the lungs were removed for determination of the wet to dry weight ratio ( W/D ratio) , expression of intercellular adhesion molecule-1 ( ICAM-1) and vascular cell adhesion molecule-1 ( VCAM-1) ( by real-time polymerase chain reaction) , and expression of calcineurin and NFATc4 in lung tissues ( using Western blot ) . Results Compared with group C, the W/D ratio, lung injury scores and concentrations of IL-1β, IL-6 and TNF-αin BALF were significantly increased, and the expression of CaN, NFATc4, ICAM-1 mRNA and VCAM-1 mRNA was up-regulated in group VILI ( P＜0. 05) . Compared with group VILI, the W/D ratio, lung injury scores and concentrations of IL-1β, IL-6 and TNF-αin BALF were significantly decreased, and the expres-sion of CaN, NFATc4, ICAM-1 mRNA and VCAM-1 mRNA was down-regulated in group CsA+VILI ( P＜0. 05) . Conclusion CaN/NFATc4 signaling pathway mediates inflammatory responses in lung tissues of rats with VILI.
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OBJECTIVE:To explore the effects of Xuesaitong injection on related indexes of patients with acute ST segment el-evation myocardial infarction(STEMI)before percutaneous coronary intervention(PCI). METHODS:112 STEMI patients under-went PCI were analyzed retrospectively and divided into control group (48 cases) and observation group (64 cases) according to different treatment methods. Control group was given Clopidogrel sulfate tablets 300 mg and Aspirin enteric-coated tablets 300 mg orally before PCI;given conventional treatment according to patients'condition after surgery. Observation group additionally re-ceived intravenous push of Xuesaitong injection 8 mL before surgery,and Xuesaitong injection 8 mL added into Sodium chloride 250 mL intravenously,once a day after surgery,on the basis of control group. Treatment course of 2 groups lasted for 14 d. TIMI level,MPG level,the serum levels of cTnT,CKMB were observed in 2 groups before surgery,24 h after surgery;serum level of PTX-3,hs-CRP were observed before surgery,one week after surgery;LVEF,LVEDD,serum level of BNP were observed before surgery and one month after surgery;the occurrence of ADR was observed to. RESULTS:Before surgery,there was no statistical significance in TIMI level,MPG level,the serum levels of cTnT,CKMB,PTX-3 and hs-CRP,LVEF,LVEDD,serum level of BNP between 2 groups (P>0.05). 24 h after surgery,TIMI level and MPG level of 2 groups were significantly higher than be-fore,and the observation group was significantly higher than the control group;the serum levels of cTnT and CKMB in 2 groups were significantly lower than before,and the observation group was significantly lower than the control group,with statistical sig-nificance(P0.05). CONCLUSIONS:Based on convention-al treatment,Xuesaitong injection can effectively improve myocardial blood supply before PCI,decrease the level of inflammatory factor,relieve myocardial injury,improve cardiac function without increasing the incidence of ADR.
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Aim To investigate the protective effect of compound total flavonoids on atherosclerosis in ApoE -/- knockout mice.Methods Seven-week old C57BL/6 mice considered of the normal group (n =1 5 );seven-week old ApoE -/- mice were fed with high-fat diet and were assigned randomly into 5 groups:model group,simvastatin group,the low com-pound flavonoids group,the middle compound fla-vonoids group and the high compound flavonoids group.After 1 6 weeks,mice serum and aortas were harvested.The formation of atherosclerotic plaque was analyzed by HE staining,The serum level of lipids pro-files and superoxide dismutase (SOD )were deter-rnined.The levels of IL-1 βand NF-κB in serum were detected by ELISA assay.Results Area of atheroscle-rotic lesion was significantly less in the compound fla-vones group than in model.The level of TC,TG,LDL-C,IL-1 β,NF-κB in serum of the compound flavonoids group were decreased significantly,while SOD and HDL-C increased significantly compared with the mod-el group,and the difference was significant (P <0.05).Conclusion The compound flavonoids have a good protective effect on early atherosclerosis in mice, which may be due to its alleviating effects on hyperlipi-demia and inflammation and oxidation.
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Aim To study the development of acute lung inflammation in mice induced by activation of the complement alternative pathway and the changes of the related indicators, and to provide an ideal pathological model of acute lung inflammation in mice for drug screening and intervention. Methods Cobra venom factor( CVF) was used to activate complement alterna-tive pathway of SPF Kunming mice by intravenous injection. According to different sampling time, the mice were divided into 15 min, 30 min, 1 h, 2 h, 6 h group, and the parallel PBS control groups were set at the same time. Lung coefficient, lung water content, myeloperoxidase ( MPO ) activity, BALF cell number and protein content were tested. The pathological changes of lung tissue were observed by HE staining. The concentration of IL-6 , TNF-α, P-selectin and ICAM-1 in bronchoalveolar lavage fluid ( BALF ) and serum were determined by ELISA. Results CVF caused pulmonary inflammatory cell infiltration in mice obviously. Compared with PBS groups, MPO activity of lung tissue, BALF cell and the protein concentration were significantly increased. The contents of IL-6, TNF-α, P-selectin in BALF and serum were in-creased, and the content of ICAM-1 in serum was also increased. The content of P-selectin in BALF reached the first peak at 30 min point, the content of IL-6 and TNF-α in BALF reached the first peak at 1 h point, but the indicators had no further changes at 2 h point, and all the indicators rose again at 6 h point. The lev-els of IL-6 and TNF-α in serum reached peak at 1 h point,then the content showed lower levels at the sub-sequent time points. The levels of P-selectin and ICAM-1 in serum increased along the time. Lung coef-ficient, lung water content and ICAM-1 of the BALF showed no significant alteration. Conclusion The ac-tivation of the complement alternative pathway can lead to acute lung inflammation in mice and the inflammato-ry response is the most obvious at 30 min to 1 h. The study could provide an ideal pathological model of a-cute lung inflammation in mice for drug screening and intervention.
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Aim To detect the possible ameliorative effects of APS on the airway inflammation and whether the effects are associated with inhibiting the NF-κB/MAPK signaling pathway in ovalbumin( OVA)-induced asthmatic rats. Methods Asthma was induced by OVA sensitization and challenge. The asthmatic rats in the APS group were treated with APS. Pulmonary in-flammation was assessed with hematoxylin and eosin staining and inflammatory cell counting in BALF. Ul-trastructural changes of type I pneumocyte were ob-served by electron microscopy. Levels of NF-κB p65, p-NF-κB p65, p-IκBα, ERK1/2, p-ERK1/2, JNK, p-JNK, p38 MAPK, p-p38 MAPK, IL-1β, IL-4, IL-5 , IL-6 and IL-13 were measured using ELISA to as-sess the activity of NF-κB/ MAPK signaling pathway. Results Compared to the normal group, OVA in-duced significantly pulmonary inflammation and ultra-structural changes of type I pneumocyte in the asthma group. Besides, OVA increased the activity of the NF-κB/MAPK signaling pathway and promoted the produc-tion of inflammatory cytokines IL-1β, IL-4 , IL-5 , IL-6 and IL-13 in the asthma group. If compared to the asthma group, APS markedly attenuated the pulmonary inflammation and type I pneumocyte damage, as well as inhibited the activity of the NF-κB/MAPK signaling pathway and decreased the production of inflammatory cytokines in the APS group. Conclusion The amelio-rative effects of APS on airway inflammation might be associated with the inhibition of the activity of the NF-κB/MAPK signaling pathway.
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Aim To investigate whether nicorandil (Nic)protects H9c2 cardiac cells against high glucose (HG)-induced injury and inflammation by inhibiting nuclear factor-κB (NF-κB )/cyclooxygenase-2 (COX-2 )pathway.Methods Cell viability was measured by cell counter kit-8 (CCK-8)assay.The expression lev-els of NF-κB,COX-2 and cleaved caspase-3 were de-termined by Western blot.The activity of lactate dehy-drogenase (LDH)in the culture medium was measured with commercial kits.The intracellular level of reactive oxygen species (ROS)was detected by 2′,7′-dichlor-fluorescein-diacetate (DCFH-DA)staining followed by photofluorography.The number of apoptotic cells was observed by Hoechst 33258 nuclear staining followed by photofluorography.Mitochondrial membrane poten-tial (MMP)was examined by rhodamine 123 staining followed by photofluorography.The secretion levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA.Results After H9 c2 cardiac cells were treated with 35 mmol · L-1 glucose (high glucose,HG)for 24 h,the cell viability was significantly decreased .Pre-treatment of the cells with 20~100 μmol·L-1 Nic for 60 min or 50 μmol· L-1 Nic for 30~120 min before exposure to HG signif-icantly attenuated the decrease in viability induced by HG.On the other hand,HG increased the expression levels of phosphorated (p)-NF-κB p65 and cyclooxy-genase-2 (COX-2 )in H9c2 cardiac cells.Pre-treat-ment of the cells with 50 μmol·L-1 Nic for 60 min at-tenuated the up-regulation of p-NF-κB p65 and COX-2 expression levels induced by HG.Furthermore,HG induced considerable injuries and inflammatory re-sponse,leading to increases in LDH activity,ROS generation,MMP loss,the number of apoptotic cells, the expression of cleaved caspase-3 as well as the se-cretion levels of IL-1βand TNF-α.Pre-treatment of the cells with 50 μmol·L-1 Nic for 60 min before HG exposure,or co-treatment of the cells with 100 μmol· L-1 PDTC (an inhibitor of NF-κB)or 10 μmol·L-1 NS-398 (an inhibitor of COX-2)and HG for 24 h ob-viously reduced the above injuries and inflammatory re-sponse induced by HG. Conclusion Nic protects H9 c2 cardiac cells against HG-induced injury and in-flammation by inhibiting NF-κB/COX-2 pathway.
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Aim To explore the inhibitory effect of li-gustrazine combined with paeonol on rat liver fibrosis induced by CCl4 and its mechanisms,so as to provide new treatment strategies for liver fibrosis in clinical. Methods Cleaning laboratory male SD rats were ran-domly divided into blank control group,model group (CCl4 ),ligustrazine group,paeonol group and combi-nation group (ligustrazine+paeonol).HE staining was used to observe the pathological change.Masson stai-ning and Sirius red staining was used to observe the collagen deposition.The levels of serum ALT,AST, ALP and hydroxyproline were detected by automatic bi-ochemistry analyzer.Western blot detected the markers of liver fibrosis.HSC-T6 cell was divided into model group,ligustrazine group,paeonol group and combina-tion group.The protein and gene expression of inflam-mation and apoptosis pathway was analyzed by Western blot and real time-PCR.Results Ligustrazine com-bined with paeonol could significantly improve liver tis-sue pathology changes caused by CCl4 .It could reduce serum ALT, AST, ALP and hydroxyproline levels. Moreover,it could also inhibit liver fibrosis marker protein expression,and thus reduce the deposition of collagen fibers.The effect was better than that in sin-gle intervention group.Combination group could inhib-it the inflammatory pathways related protein expression in HSC cells and promote the apoptosis of HSC cells. Conclusion Ligustrazine in combination with paeonol has significant anti-fibrosis effect,and the effect is bet-ter than both single intervention.The effect may be due to the interference with TNF-α/NF-κB pathway in the HSC cells,which promotes its apoptosis and inhib-its the generation of extracellular matrix.
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Aim To investigate the effect of Salvianol-ic acid A (Sal A)on mice with isoproterenol (ISO)-induced myocardial infraction and its possible mecha-nisms.Methods The mice were subcutaneously in-jected with ISO (8 mg·kg-1 )to induce myocardial in-farction.The myocardial protective effect of Salvianolic acid A was evaluated from mortality rate,electrocardio-gram (ECG),heart function,myocardial infarction in-dex,serum myocardial enzymes and its action mecha-nisms were explored from inflammation,anti-oxidation and cells apoptosis.Results Salvianolic acid A dose-dependently enhanced the heart function of myocardial infarction mice,reduced the heart index,inhibited the myocardial enzyme leakage,showed obvious myocardi-al protection effects.ELISA results showed that Salvi- anolic acid A could reduce the expression of myocardial inflammatory cytokines such as IL-6(interleukin-6,IL-6),TNF-α(tumornecrosis factor-α,TNF-α).West-ern-blotting confirmed that Salvianolic acid A could in-crease the expression of anti-apoptotic proteins Bcl-2, reduce the expression of apoptosis protein Bax,and raise the phosphorylation level of PI3K and Akt.Con-clusion Salvianolic acid A displays a significant pro-tective effect against isoproterenol-induced myocardial infarction and its mechanism may be related to the in-crease of PI3K/Akt signal pathway and the inhibition of cell apoptosis and inflammatory reaction.
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Objective Inflammation plays a critical role in the presence , development and maintenance of atrial fibrillation ( AF) , but it remains unclear what factors induce inflammation in AF patients , especially in those with valvular heart disease ( VHD) . The aim of this paper was to investigate the role of the shedding of Syndecan -4 in left atrial inflammation in patients with valvular atrial fibrillation. Methods Sixty VHD patients scheduled for valvuloplasty or valve replacement surgery were divided into three groups of equal number:sinus rhythm (SR), paroxysmal atrial fibrillation (PaAF), and persistent atrial fibrillation (PeAF).Another 10 pa-tients with congenital heart disease but no valve damage and atrial fibrillation were included in a control group .Baseline clinical data were recorded and tissues were obtained from the left atrial appendage during operation .The expressions of iNOS , HMGB1, and Syn-decan-4 in the left atrium were detected by Western blot , and the pathological changes of the left atrial tissue observed by HE staining . Results Western blot analysis was performed to detect expression levels of proteins .The iNOS level was significantly higher in pa-tients from the paroxysmal AF group (1.61 ±0.10) and persistent AF group (1.67 ±0.08) than those from sinus group (1.06 ± 0.11) and control group (1.02 ±0.12), as was the protein level of HMGB1 (0.63 ±0.05, 0.95 ±0.10, 0.45 ±0.07 and 0.46 ± 0.06 in paroxysmal AF group, persistent AF group, sinus group and controlgroup respectively ).Inflammatory cell infiltration in-creased, while syndecan 4 was down-regulated in AF groups.All these comparisons were significant (P<0.05). Conclusion The decreased expression of Syndecan-4 and enhanced inflammatory response in the left atrial tissue indicate that the shedding of Synde-can-4 may play a role in the presence and development of inflamma-tion in the left atrium .
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Aim To investigate the effects of Vam3 on ATP-induced inflammatory response in macrophages and the underlying mechanisms. Methods LPS primed mouse peritoneal macrophages were stimulated with ATP,and IL-1βlevel in supernatants was meas-ured by ELISA.Activity of caspase 1 was measured u-sing caspase 1 activity assay kit.Reactive oxygen spe-cies (ROS )level was detected with fluorescent probe DCFH-DA.MTT assay was used to detect cell prolifer-ation,and intracellular Ca2+concentration was meas-ured using laser scanning confocal microscope.Results Extracellular ATP led to increase in IL-1βrelease, caspase 1 activity and ROS production.It also led to rapid increase in intracellular Ca2+concentration and induced cell death.These effects were inhibited by Vam3 .Conclusion Vam3 inhibits ATP-induced in-flammatory response in macrophages,which may sug-gest the blocking effect of Vam3 on caspase 1 ~IL-1βinflammatory signaling pathway in macrophages.
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Objective To investigate the effect oflevecamitine on nutrition,microinflammation status in ma-intenance hemodialysis (MHD) patients. Methods Forty two MHD patients were selected, who had undergone he-modialysis for at least two months before the study. One gram of levoeamitine was injecfed to the patients at the end of each dialysis treatment for six months. The parameters of inflammation stress were studied. Results After treatment with levocarnitine for six months, the average levels of dry body weight decreased markedly. ( P<0.05 ), The aver-age serum levels of C2reaetive protein (CRP),interleuldn26 (IL26) ,tumor necrosis factor2α(TNF2α), (P<0.01 ). Difference was not significant between serum lipid parameters before and after the treatment. Conclusion Intravenous supplement with levocamitine in MHD patients, appears to be associated with an improvement of nutrition and mieroinflammation status.