ABSTRACT
Objective :To explore influence of ticagrelor on levels of serum high sensitive C reactive protein (hsCRP) and plasma homocysteine (Hcy) in patients with acute coronary syndrome (ACS).Methods :A total of 135 ACS pa‐ tients hospitalized in our department from Jan 2016 to Feb 2017 were selected .Based on routine treatment ,Patients were randomly and equally divided into routine group ,clopidogrel group and ticagrelor group (based on routine treatment respectively received clopidogrel or ticagrelor ) for four weeks .Levels of serum hsCRP and plasma Hcy were measured and compared among all groups before and after treatment .Results :Compared with before treat‐ment ,after four‐week treatment , there were significant reductions in levels of serum hsCRP and plasma Hcy in three groups (P＜0. 05 or ＜0.01).Compared with routine group and clopidogrel group after four‐week treatment , there were significant reductions in levels of serum hsCRP [ (12.95 ± 1.99) mg／L , (8. 56 ± 1. 24) mg／L vs.(4. 47 ± 1. 92) mg／L] and plasma Hcy [ (13.48 ± 2.12) μmol／L , (9.55 ± 0. 94) μmol／L vs.(6. 61 ± 1. 15) μmol／L] in ticagrelor group ( P＜0.05 or ＜0.01).Conclusion :Ticagrelor can significantly reduce levels of serum hsCRP and plasma Hcy while effective antiplatelet therapy ,then significantly inhibit inflammatory response ,improve vascular endothelial function ,contribute to stabilizing atherosclerotic plaques ,improve prognosis in ACS patients .
ABSTRACT
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.
ABSTRACT
AIM:To investigate whether angiotensin-(1-7) [Ang-(1-7)] protects H9c2 cardiac cells against high glucose (HG)-induced injury and inflammation by inhibiting the interaction between Toll-like receptor 4 (TLR4) acti-vation and necroptosis .METHODS:The expression levels of receptor-interacting protein 3 ( RIP3;an indicator of necrop-tosis) and TLR4 were determined by Western blot .Cell viability was measured by CCK-8 assay.The activity of lactate de-hydrogenase ( LDH) in the culture medium was measured with a commercial kit .The releases of interleukin-1β( IL-1β) and tumor necrosis factor-α( TNF-α) were measured by ELISA .The intracellular level of reactive oxygen species ( ROS) was analyzed by 2 ’ , 7 ’-dichlorfluorescein-diacetate ( DCFH-DA ) stating followed by photofluorography .Mitochondrial membrane potential ( MMP) was examined by rhodamine 123 staining followed by photofluorography .RESULTS:After the H9c2 cardiac cells were treated with HG (35 mmol/L glucose) for 24 h, the expression of RIP3 was obviously increased . Co-treatment of the cells with 30μmol/L TAK-242 (an inhibitor of TLR4) attenuated the up-regulation of RIP3 induced by HG.Furthermore, the expression of TLR4 was significantly increased after the cells were exposed to HG for 24 h, and co-treatment of the cells with 100μmol/L necrostatin-1 ( Nec-1;a specific inhibitor of necroptosis ) and HG for 24 h attenua-ted the up-regulation of TLR4 expression induced by HG .Moreover, 1μmol/L Ang-(1-7) simultaneously blocked the up-regulation of the RIP3 and TLR4 induced by HG.On the other hand, co-treatment of the cells with 1μmol/L Ang-(1-7), 30 μmol/L TAK-242 or 100 μmol/L Nec-1 and HG for 24 h attenuated HG-induced injuries and inflammatory response , leading to the increase in the cell viability , and the decreases in the activity of LDH , ROS generation , MMP loss as well as the releases of IL-1βand TNF-α.CONCLUSION:Ang-(1-7) protects H9c2 cardiac cells against HG-induced injury and inflammation by inhibiting the interaction between TLR 4 activation and necroptosis .
ABSTRACT
AIM:Tostudywhe ther theangiotens in-(1-7)[Ang-(1-7)]/Mas receptor axis protects cardio-myocytes against high glucose (HG)-induced injury by inhibiting nuclear factor-κB (NF-κB) pathway.METHODS:The cell viability was measured by CCK-8 assay.The intracellular levels of reactive oxygen species ( ROS) were detected by DCFH-DA staining .The number of apoptotic cells was tested by Hoechst 33258 nuclear staining .Mitochondrial membrane potential ( MMP) was examined by JC-1 staining.The levels of NF-κB p65 subunit and cleaved caspase-3 protein were de-termined by Western blotting.RESULTS: Treatment of H9c2 cardiac cells with 35 mmol/L glucose (HG) for 30, 60, 90, 120 and 150 min significantly enhanced the levels of phosphorated ( p) NF-κB p65, peaking at 60 min.Co-treatment of the cells with 1 μmol/L Ang-(1-7) and HG for 60 min attenuated the up-regulation of p-NF-κB p65 induced by HG. Co-treatment of the cells with Ang-(1-7) at concentrations of 0.1~30μmol/L and HG for 24 h inhibited HG-induced cy-totoxicity, evidenced by an increase in cell viability .On the other hand, 1 μmol/L Ang-(1-7) ameliorated HG-induced apoptosis, oxidative stress and mitochondrial damage , indicated by decreases in the number of apoptotic cells , cleaved caspase-3 level, ROS generation and MMP loss .However, the above cardioprotective effects of Ang-(1-7) were markedly blocked by A-779, an antagonist of Ang-(1-7) receptor (Mas receptor).Similarly, co-treatment of H9c2 cardiac cells with 100 μmol/L PDTC ( an inhibitor of NF-κB) and HG for 24 h also obviously reduced the above injuries induced by HG.CONCLUSION:Ang-(1-7)/Mas receptor axis prevents the cardiomyocytes from the HG-induced injury by inhibiting NF-κB pathway .
ABSTRACT
AIM:To investigate the effect of atorvastatin on myocardial apoptosis , ventricular remodeling and cardiac function after acute myocardial infarction (AMI) in diabetic rats, and to explore whether the effect is mediated by hepatocyte growth factor ( HGF)/c-Met signaling pathway .METHODS:Diabetes in 70 male SD rats was induced by in-traperitoneal injection of streptozotocin (STZ, 65 mg/kg).After 8 weeks, AMI was induced by the ligation of the left ante-rior descending coronary artery in the diabetic rats , and 32 surviving rats were divided into AMI group (n=16) and AMI+atorvastatin group ( n=16, 20 mg· kg -1 · d-1 ) at random.The similar surgical procedure was completed in sham group (n=11) without coronary ligation.Atorvastatin was given daily by gavage from the first day after AMI .Two weeks later, the cardiac function , pathological changes of myocardial tissues , myocardial apoptosis , and the expression of HGF and c-Met were compared among groups .RESULTS: AMI significantly reduced cardiac function , increased collagen volume fraction ( CVF) and myocardial apoptotic index , and up-regulated the expression of HGF and c-Met at mRNA and protein levels in AMI control group (P<0.05).The cardiac function was improved , and CVF and myocardial apoptotic index were reduced by the treatment with atorvastatin , which also up-regulated the expression of HGF and c-Met (P<0.05).CON-CLUSION:Atorvastatin significantly attenuates myocardial apoptosis and cardiac remodeling , and improves cardiac func-tion after AMI in diabetic rats by further enhancing the activation of HGF /c-Met pathway .
ABSTRACT
Objective To investigate the effects of Buyanghuanwu decoction on infiltration of neutrophils and expression of ICAM-1 after middle cerebral artery occlusion (MCAO) in rats. Methods Rats were pretreated with Buyanghuanwu decoction(13 g/kg and 26 g/kg) for 7d and then subjected to cerebral ischemia/reperfusion injury induced by an MCAO. After a 90min ischemia and a 24h reperfusion, the neurological deficit and the survival neurons were determined. The effects of Buyanghuanwu decoction on infiltration of neutrophils and expression of ICAM-1 by immunohistochemistry are evaluated. Results Buyanghuanwu decoction significantly ameliorated the neurological deficit and increased survival neurons . The myeloperoxidase (MPO) positive cells and the ICAM-1 positive vessels in the vehicle-treated rats were increased significantly (P