Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

骨调素和单核细胞趋化蛋白在大鼠梗阻性肾病中的表达及可能作用

目的:探讨骨调素(OPN)和单核细胞趋化蛋白(MCP-1)在大鼠梗阻性模型中的表达及其在肾脏纤维化发病机制中的作用.方法:采用-单侧输尿管结扎制造梗阻性肾病模型,分别于造模后7 d、14 d取肾组织,应用HE染色观察肾脏病理改变,免疫组化方法检测肾组织畔OPN和MCP-1蛋白的表达,应用逆转录-聚合酶链式反应(RT-PCR)法观察肾组织中OPN mRNA和MCP-1 mRNA的变化.结果:OPN、MCP-1表达主要位于肾小管上皮细胞,随着梗阻时间的延长,肾组织中OPN、MCP-1蛋白和mRNA表达明显增加.结论:OPN、MCP-1蛋白和mRNA在梗阻性肾病大鼠肾组织表达明显增加介导炎症过程,参与肾间质纤维化.     

CD14+单核细胞人类白细胞抗原DR表达率与脓毒症关系的研究

目的了解烧伤延迟复苏时CDl4^＋单核细胞人类白细胞抗原DR（HLA—DR）表达率的变化，分析其与脓毒症的关系。方法选择烧伤面积大于30％TBSA的25例烧伤延迟复苏患者，于伤后1、3、7、14、28d取外周血，其中7例患者住院期间并发脓毒症，于脓毒症发生后连续2d亦取其外周血。另取20例健康体检者外周血作为对照。流式细胞仪检测CD14^＋单核细胞HLA．DR表达率，酶联免疫吸附测定法检测血浆中肿瘤坏死因子α（TNF—α）、白细胞介素10（IL-10）的浓度。结果非脓毒症患者伤后1、3、7、14、28dCD14^＋单核细胞HLA—DR表达率分别为（15±6）％、（74±5）％、（264±17）％、（284-16）％、（474-16）％，明显低于健康体检者[（924±10）％，P〈0．01]；脓毒症患者发生脓毒症后1、2d，该指标亦明显低于健康体检者及非脓毒症患者伤后1、7、14、28d（P〈0．01）。脓毒症患者TNF—d检出率及TNF—α、IL-10浓度，均高于非脓毒症患者和健康体检者（P〈0．05或P〈0．01）。伤后1、7、28d，外周血CD14^＋单核细胞HLA—DR表达率与IL—10浓度呈显著负相关（r分别为-0．9963、-0．7459、-0．8474，P〈0．01）。结论烧伤延迟复苏患者免疫功能低下，促炎性介质释放量增加，并发脓毒症时则更为严重。外周血CD14^＋单核细胞HLA—DR表达率可作为动态检测患者免疫功能状态的有效指标。     

颈动脉粥样硬化斑块内MCP-1表达的研究

目的观察颈动脉粥样硬化(AS)斑块内单核细胞趋化蛋白-1(MCP-1)的mRNA和抗原的表达情况。方法分别应用原位杂交和免疫组织化学法测定颈AS斑块中MCP-1mRNA和抗原表达。结果相对于正常动脉内膜,颈AS病变内膜MCP-1阳性细胞数明显增多(P<0.05)。其中颈AS严重病变肩区阳性细胞数最多,以单核-巨噬细胞为主。结论MCP-1与颈AS发生密切相关。     

Generation of antigen-specific CD4+ T cell lines from naive precursors

The conditions required for sensitizing naive T cells to nominal antigen are poorly understood. In this report we describe an in vitro system for generating antigen-specific CD4⁺ T cells from previously unprimed individuals. Freshly isolated CD4⁺ T cells were cultured with keyhole limpet hemocyanin (KLH), sperm whale myoglobin (SWM), or human immunodeficiency virus (HIV) gp 160, antigens to which most persons have not been sensitized, in the presence of either dendritic cells (DC) or macrophages (MΦ). In short-term (< 8 days) cultures, CD4⁺ T cells or their CD4⁺, CD45RA (naive) subpopulation mounted significant proliferative responses to KLH, SWM, and HIV gp160, but only if the antigens were presented by DC. In contrast, CD4⁺, CD45RO (memory) T cells responded poorly to these antigens, although they responded vigorously to tetanus toxoid, a recall antigen, presented by either DC or MΦ. KLH- and SWM-specific CD4⁺ T cell lines were established from the starting population that had been sensitized in vitro, following repeated stimulation with antigen and MΦ in medium supplemented with interleukin-2 and interleukin-4. Despite the continued presence of these cytokines during T cell expansion, the expanded lines retained their ability to respond to the priming antigen in the absence of exogenous cytokines. When the CD45RA and CD45RO subpopulations were sensitized and expanded separately, the CD45RA cells alone gave rise to antigen-specific T cell lines, while the CD45RO cells proliferated nonspecifically. These results demonstrate that human naive CD4⁺ T cells can be sensitized in vitro to nominal antigens presented by DC and that the sensitized cells can be expanded into long-term lines that retain their antigen specificity.     

Remarkable correlation between increased HLA-DQ antigen positive monocytes and prognosis of renal transplantation

Since cyclosporin A (CsA), a widely used immunosuppressive drug, strongly suppresses interleukin-2 (IL-2) secretion, it is frequently difficult to estimate T lymphocyte activation in early acute rejection. We found that, when evaluated based on HLA-DQ antigen expression, monocyte activation in the peripheral blood of renal transplantation patients was a very sharp parameter in diagosing acute rejection. All of 16 episodes of early acute rejection, which were relatively easily suppressed by steroid pulse therapy, showed a sharp increase in the proportion of HLA-DQ antigen-positive monocytes (DQ⁺ mono) and a quick return of DQ⁺ mono to previous values, along with a fall in serum creatinine levels. Since, however, HLA-DR antigen-positive T lymphocytes (DR ⁺T) were markedly increased over a long period in episodes of therapy-resistant and chronic rejection, their prolonged high value was regarded as a parameter indicative of poor prognosis.     

缬沙坦对糖尿病大鼠心肌MCP-1表达的影响

目的　研究缬沙坦对糖尿病大鼠心肌MCP -1表达的影响。方法　将Wistar大鼠随机分成三组 :正常对照组 (NC组 )、糖尿病模型组 (DM组 )、糖尿病模型 +缬沙坦治疗组 (DV组 ) ,用STZ诱导糖尿病大鼠模型 ,于 8周后用免疫组织化学的方法检测糖尿病大鼠和缬沙坦干预的糖尿病大鼠心肌组织中MCP -1的表达。结果　 8周时心肌组织中MCP -1的表达DM组明显高于DV组、NC组 (P <0 0 1) ,DV组明显高于NC组 (P <0 0 1)。结论　缬沙坦能显著减少糖尿病大鼠心肌组织中MCP -1的表达     

Monocytes in active multiple sclerosis: intact regulation of HLA-DR density in vitro despite decreased HLA-DR density in vivo

HLA-DR expression on circulating monocytes varies as a function of disease activity in patients with multiple sclerosis (MS), a putative immunopathological demyelinating disorder. Specifically, monocytes isolated from subjects with active MS exhibit reduced HLA-DR antigen density, and immunoregulatory aberrations such as impaired T lymphocyte-mediated suppression correlate strongly with this quantitative defect. To address the mechanism underlying this phenomenon, we compared in vitro regulation of HLA-DR by interferon beta (IFN beta), interferon gamma (IFN gamma), and lipopolysaccharide (LPS) in monocytes from patients with stable and active MS and normal individuals. Interferon-gamma and LPS enhanced monocyte expression of HLA-DR equally in both MS patient groups, suggesting that underexpression of HLA-DR in active MS was not explained by impaired in vivo monocyte responsiveness. Furthermore, interferon regulation of HLA-DR in normals and stable MS subjects was indistinguishable, indicating that aberrant interferon-mediated regulation of class II major histocompatibility complex (MHC) on circulating monocytes does not appear to be a characteristic of the MS disease state.     

Influence of bradykinin B1 and B2 receptors in the immune response triggered by renal ischemia–reperfusion injury

Bradykinin B1 receptors are exclusively expressed in inflamed tissues. For this reason, they have been related with the outcomes of several pathologies. Ischemia–reperfusion injury is caused by the activation of inflammatory and cytoprotective genes, such as macrophage chemoattractant protein-1 and heme oxygenase-1, respectively. This study was aimed to analyze the involvement of bradykinin B1 and B2 receptors (B1R and B2R) in tissue response after renal ischemia–reperfusion injury. For that, B1R (B1−/−), B2R (B2−/−) knockout animals and its control (wild-type mice, B1B2+/+) were subjected to renal bilateral ischemia, followed by 24, 48 and 120 h of reperfusion. At these time points, blood serum samples were collected for creatinine and urea dosages. Kidneys were harvested for histology and molecular analyses by real-time PCR. At 24 and 48 h of reperfusion, B1−/− group resulted in the lowest serum creatinine and urea levels, indicating less renal damage, which was proved by renal histology. Renal protection associated with B1−/− mice was also related with higher expression of HO-1 and lower expression of MCP-1. In conclusion, the absence of B1R had a protective role against inflammatory responses developed after renal ischemia–reperfusion injury.     

氯沙坦通过下调单核细胞趋化蛋白1受体表达抑制单核细胞活化

目的探讨血管紧张素Ⅱ对单核细胞趋化蛋白1受体CCR2表达的影响及氯沙坦的干预作用。方法人单核细胞株与血管紧张素Ⅱ(10-7mol/L)孵育,加或不加氯沙坦(10-7、10-6和10-5mol/L),检测上清液中单核细胞趋化蛋白1水平、单核和内皮细胞粘附情况以及CCR2mRNA的表达。结果与对照组比较,血管紧张素Ⅱ明显增加单核细胞培养上清液中单核细胞趋化蛋白1水平(26.46±3.58ng/L比10.56±2.34ng/L,P<0.01),增加单核内皮细胞间粘附(596±27比268±16,P<0.01)。血管紧张素Ⅱ刺激细胞后明显上调CCR2mRNA表达,氯沙坦能显著抑制血管紧张素Ⅱ的作用,降低单核细胞趋化蛋白1的水平,减少单核内皮细胞间粘附,下调CCR2 mRNA表达。结论氯沙坦通过下调单核细胞趋化蛋白1受体CCR2基因表达抑制单核细胞活化。