黄芩苷对大鼠局灶性短暂性脑缺血再灌继发炎性损伤的保护作用(英文)

目的研究黄芩苷对大鼠短暂性脑缺血再灌损伤的保护作用是否与其调节炎症因子和粘附分子的表达有关。方法线栓法制备大脑中动脉阻断短暂局灶性脑缺血模型,缺血2 h,再灌注24 h。评价神经功能状态和脑梗死体积;用免疫组化、分光光度法测定组织细胞间粘附分子(ICAM)1表达和髓过氧化物酶活性;HE染色观察组织炎性细胞浸润;RT-PCR、免疫印迹和放免法分别测定大脑缺血皮质诱导型一氧化氮合酶(iNOS)、核因子κB(NF-κB)和白细胞介素1(IL-1)的表达。结果黄芩苷能显著降低大鼠短暂性脑缺血后皮质梗死体积,改善神经功能状态,抑制ICAM-1,iNOS和NF-κB表达,降低缺血皮质IL-1含量,与模型组相比具有显著性差异。结论黄芩苷通过抑制炎性介质的表达和释放对大鼠短暂性脑缺血损伤具有保护作用。

NF-κB-p65、ICAM-1和细胞凋亡在力竭性运动诱发延迟性心肌损伤中的作用

目的:观察反复力竭性游泳运动后,不同时相大鼠心肌组织中核转录因子-κB(NF-κB)-p65、细胞间黏附因子-1(ICAM-1)和细胞凋亡的动态变化,以评价在运动延迟性心肌损伤中的作用。方法:采用反复力竭性游泳运动建立延迟性心肌损伤大鼠模型。将无训练的80只Wistar雄性大鼠随机分为安静对照组和反复力竭性运动后即刻组、3 h组、6 h组、12 h组、24 h组、48 h组和96 h组。每组10只大鼠(n=10)。分别于末次运动后即刻、3、6、12、24、48 h和96 h快速取出心脏,应用免疫组化染色法和DNA原位末端标记(TUNEL)法检测大鼠心肌组织中NF-κB-p65和ICAM-1表达的水平和细胞凋亡的动态变化。结果:与安静对照组比较,反复力竭性运动后不同时相大鼠心肌细胞中NF-κB-p65和ICAM-1蛋白的表达及细胞凋亡指数均显著增加(分别为P<0.05和P<0.01),其中心肌细胞中NF-κB-p65的表达和细胞凋亡于运动后48 h达高峰,ICAM-1蛋白的表达于运动后即刻达高峰,运动后96 h有所减轻。结论:反复力竭性运动可以造成早期心肌缺血缺氧损伤,刺激心肌细胞中NF-κB-p65和ICAM-1表达的水平的升高,促进炎症反应,并诱导心肌细胞凋亡,进一步加重运动后早期心肌损伤,诱发延迟性心肌损伤。

Pre-diagnostic levels of adiponectin and soluble vascular cell adhesion molecule-1 are associated with colorectal cancer risk

AIM： To examine the relationships between pre-diag- nostic biomarkers and colorectal cancer risk and assess their relevance in predictive models.METHODS： A nested case-control study was designed to include all first primary incident colorectal cancer cases diagnosed between inclusion in the SUpplemen- tation en VItamines et Min^raux AntioXydants cohort in 1994 and the end of follow-up in 2007. Cases （n = 50） were matched with two randomly selected con- trols （n = 100）. Conditional logistic regression models were used to investigate the associations between pre- diagnostic levels of hs-CRP, adiponectin, leptin, soluble vascular cell adhesion molecule-1 （sVCAM-1）, soluble intercellular adhesion molecule-I, E-selectin, monocyte chemoattractant protein-1 and colorectal cancer risk. Area under the receiver operating curves （AUC） and relative integrated discrimination improvement （RIDI） statistics were used to assess the discriminatory poten- tial of the models. RESULTS： Plasma adiponectin level was associated with decreased colorectal cancer risk （P for linear trend -- 0.03）. Quartiles of sVCAM-1 were associated with increased colorectal cancer risk （P for linear trend = 0.02）. No association was observed with any of the other biomarkers. Compared to standard models with known risk factors, those including both adiponectin and sVCAM-1 had substantially improved performance for colorectal cancer risk prediction （P for AUC improve- ment = 0.01, RIDI = 26.5%）. CONCLUSION： These results suggest that pre-diag- nostic plasma adiponectin and sVCAM-1 levels are as- sociated with decreased and increased colorectal cancer risk, respectively. These relationships must be confirmed in large validation studies.

Circulating Adhesion Molecules in Patients with Keshan Disease and Their Relationship with Coxsackie B Virus Infection

This study determined the levels of serum soluble intercellular adhesion molecule-1 （sI-CAM-l） and soluble vascular cell adhesion molecular-1 （sVCAM-1） in patients with different types of Keshan disease （KD）, examined the relationship between Coxsackie B virus-specific IgM antibody （CBV-IgM） and slCAM-1 or sVCAM-1 in KD patients, and investigated the role of these adhesion molecules in the pathogenesis of KD and their clinical implications. The levels of serum slCAM-1, sVCAM-1 and CBV-IgM were measured by using enzyme-linked immunosorbent assay in 22 patients with chronic Keshan disease （CKD）, 27 with latent Keshan disease （LKD） and 28 healthy controis. The subjects in different groups were adjusted for sex and age. Echocardiography was adopted to determine left ventricular ejection fraction （LVEF） in 22 patients with CKD. The results showed that CKD patients had significantly higher levels of slCAM-1 and sVCAM-1 than LKD patients and healthy controls （P〈0.01 for all）. And there was significant difference in the levels of the 2 adhesion molecules between LKD patients and healthy controls （P〈0.05）. A negative correlation was found between LVEF and slCAM-1 or sVCAM-1 in CKD patients. The percentage of CBV-specific IgM positive individuals in KD patients was significantly higher than that of healthy controls. In CVB-specific IgM positive patients, the levels of serum slCAM-1 and sVCAM-1 were significantly greater than those in CBV-specific IgM negative counterpart. It was concluded that the increase in the levels of slCAM-1 and sVCAM-1 suggests the progression of inflammation in KD. slCAM-1 and sVCAM-1 can promote the development of myocardial pathology and lead to poor myocardial function. The increased serum slCAM-1 and sVCAM-1 in KD patients may be related to CBV infection.

Daclizumab prevents acute renal allograft rejection: 1 year analysis

Objective：To investigate the clinical effect of Daclizumab on preventing acute rejection in renal transplant recipients. Methods：71 patients were randomly divided into two groups：Daclizumab group （n =26） and control group （n = 45）. Baseline regimen of mycophenolate mofetil （MMF）, cyclosporin （CsA）, methylprednisolone （MPD） and prednisone （Pred） were administered to all patients. The treatment of Daclizumab was based on baseline regimen. The Daclizumab group received Daclizumab twice before and after renal transplant. The occurrence of post-transplantation acute rejection, renal function and T lymphocyte subtypes were sequentially monitored; meanwhile adverse events, infection episode, and patient and graft survival were observed. All of patients received a follow-up of 12 months at least. Results：The occurrence of acute rejection in Daclizumab group in 1, 3, 6 and 12 months after renal transplantation was 7.7%, 19.2%, 23.1% and 30.8%, respectively,while it was 15.6% ,28.9%, 35.6% and 46.7% in the control group. There was significant difference between the two group（P 〈 0.05）. There was no difference in infection episodes and adverse events between the Daclizumab group and control group. One year patient survival was 92.3% in Daclizumab group, 91.1% in control group （P 〉 0.05）, compared with graft survival of 96.2 % and 93.3 % for Daclizumab and control group, respectively （P 〉 0. 05）. The renal function in Daclizumab group in 1, 6 and 12 months after renal transplantation was better than that in control group （P 〈 0,05）. The CD3＋ and CD4＋ subtypes decreased in both two groups after operation but no significant difference （P 〉 0.05）. Conclusion：Daclizumab combined with MMF,CsA,MPD and Pred therapeutic regimen was effective to reduce the occurrence of acute rejection in renal transplant recipients and have no influence on T lymphocyte subtypes.

SDF-1/NELL-1双基因转染促进脂肪干细胞体外成骨

[目的]观察腺病毒载体转染基质细胞衍生因子-1 (stromal cell-derived factor-1, SDF-1)和尼尔样-1型分子(Nellike molecule-l, NELL-1)基因对兔脂肪干细胞(adipose stem cells, ADSCs)体外成骨分化能力的影响。[方法]自兔分离培养ADSCs,分为单纯细胞组(original cell control, OCC)、空质粒转染组(empty vector control, EVC)、SDF-1组、NELL-1组和SDF-1/NELL-1组,给予相应体外处理。成骨诱导14 d后,茜素红染色检测钙结节形成及碱性磷酸酶活性,Western blot检测和RT-PCR检测相应蛋白与m RNA表达水平。[结果]单纯SDF-1或NELL-1转染,或SDF-1/NELL-1两者共同转染均显著增加目标基因的蛋白表达水平(P<0.05),特别是共同转染同时增加两种基因标目蛋白的表达。茜素红染色钙结节计数和ALP活性检测方面,SDF-1组、NELL-1组和SDF-1/NELL-1组均显著高于OCC组和EVC组(P<0.05),其中,SDF-1/NELL-1组最高。RT-PCR检测方面,SDF-1组、NELL-1组和SDF-1/NELL-1组的OPN和OCN m RAN表达水平高于OCC组和EVC组(P<0.05),其中SDF-1/NELL-1组的OPN和OCN m RAN表达水平最高。[结论] SDF-1、NELL-1单独转染,或两者共转染ADSCs均可获得目标蛋白的高表达,以上两种基因单独转染,特别是两种基因共同转染,可显著增强ADSCs的体外成骨。

Effect of Moxibustion Therapy on the Serumal Intercellular Cell Adhesion Molecule and the Histopathology of Experimental Arthritis in Rats

Objective： To observe the effects of moxibustion therapy at Shenshu （BL 23） and Zusanli （ST 36） of rats with induced rheumatoid arthritis （RA） on the serumal intercellular cell adhesion molecule-1 （ICMA-1） and the pathological tissue, to discuss the mechanism of the warming and activating effect of moxibustion. Methods： After establishing the RA rats model, the induced rats were treated with moxibustion therapy on the acupoint Shenshu （BL 23） and Zusanli （ST 36）, followed by analyzing the pathological section of the ankle of the hind limb and testing the ICAM-1 content with ELISA. Results： The plantar circumferences of the induced rat increased significantly compared with the rats in the control group （P〈0.01）, accompanying with the increase of the synovial layer, the erosion of phlogocytes to chondrocytes and the specific increase of ICAM- 1 content. After the moxibustion therapy, the plantar circumferences decreased significantly （P〈0.01） while the synovial layer tended to reduce. In addition, there was no pathological damage of the articular cartilage and the ICAM content decreased with significant deviation （P〈0.01）, compared to the model group. Conclusion： It was concluded that moxibustion therapy could inhibit the arthrosynovitis and hyperplasia, ameliorate the erosion of phlogocyte to cartilage, prevent articular periosteal lesions and delay the pathological course. The warming and activating effect of moxibustion therapy may involve the inhibition of the formation of ICAM- 1 and pannus.

Immune mechanism and clinical significance of macrophage to medullary hematopoietic injury of immune-related hematocytopenia patients

Background Immune-related hematocytopenia （IRH） is considered to be related with the production of autoantibody, as well as the activation of humoral immunity which is stimulated by B lymphocyte. This study aimed to observe the levels of various cytokines in the blood serum and the in situ active state of macrophage （Me） in the medullary hematopoietic microenvironment of IRH patients, and to probe into the immune mechanism and clinical significance of Me in hematopoietic cell injury. Methods ELISA is used to detect the IL-4, IL-6, IL-12, IL-17, and IFN-y levels in the peripheral blood serum of 376 patients in pre- and post-therapy. Cytochemistry and cell immunochemistry methods are used to observe the peroxidase （POX）, nonspecific esterase （NSE）, hemosiderin granules, and HLA-DR activity of Me in the bone marrow of patients. Immunofluorescence is used to observe the expression of hemocyte antihuman globulin IgG antibody, lymphocytes CD4 molecule, Me membrane Fcyllreceptor （FcyllR）, mannitose receptor （MR）, IFN-y, ICAM-1, IL-12, and IL-17A and the formation mechanism of antibody-dependent cell-mediated cytotoxicity （ADCC） hematopoietic cell islands （HI） in the medullary hematopoietic microenvironment of patients. Glucocorticoid is used for treatment on the basis of anti-infection therapy, and gamma globulin stoss therapy is used for the appearance of ADCC-type HI or serious Me bloodthirsty phenomenon; if necessary, association of Cyclosporine A （CsA） should be used and chalybeate should be supplemented. Results In the patient group, the levels of IL-4, IL-6, IL-12, IL-17, and IFN-y were increased. After treatment, the cytokine levels gradually became normal. The activated Me in the marrow highly expressed NSE and POX, and Me swallowed more hemosiderin particles, but the iron in the cytoplasm of immature erythrocytes decreased. The activated Me expressed HLA-DR, MR, ICAM-1, IFN-y, and IL-12. For patients with humoral immunity activation and bacterial infection, Me weakly expressed IL-17A but highly expressed FcyIIR, and the phenomenon that ADCC-type HI broke pathological blood corpuscles often occurred; for the cellular immune activation along with virus infection, the white blood count （WBC） significantly reduced, Me weakly expressed FcyIIR, secretory highly expressed IL-17A, and the phenomena that Me adhered to, captured and swallowed blood cell often occurred. After four weeks of anti-infective and immunosuppressive therapy, nuclear apoptosis of Me occurred in the bone marrow of patients, HI and bloodthirsty phenomenon disappeared, and the peripheral blood picture started to improve. Conclusions Me is an important antigen presenting cell in the IRH marrow for hematopoiesis destruction and an immune effector cell of hematopoietic injury; infection can promote the activation of Me, upregulate the impression of immune molecule and receptors, form ADCC HI. aeGravate hematoBoietic iniurv, and accelerate the destruction on hematoDoietic cell.