Adhesion of different cell cycle human hepatoma cells to endothelial cells and roles of integrin β_1

AIM: To investigate the adhesive mechanical properties of different cell cycle human hepatoma cells (SMMC-7721) to human umbilical vein endothelial cells (ECV-304), expression of adhesive molecule integrinβ1 in SMMC-7721 cells and its contribution to this adhesive course. METHODS: Adhesive force of SMMC-7721 cells to endothelial cells was measured using micropipette aspiration technique. Synchronous G1 and S phase SMMC-7721 cells were achieved by thymine-2-deoxyriboside and colchicines sequential blockage method and double thymine-2-deoxyriboside blockage method, respectively. Synchronous rates of SMMC-7721 cells and expression of integrinβ1 in SMMC-7721 cells were detected by flow cytometer. RESULTS: The percentage of cell cycle phases of general SMMC-7721 cells was 11.01% in G2/M phases, 53.51% in G0/G1 phase, and 35.48% in S phase. The synchronous rates of G1 and S phase SMMC-7721 cells amounted to 74.09% and 98.29%, respectively. The adhesive force of SMMC-7721 cells to endothelial cells changed with the variations of adhesive time and presented behavior characteristics of adhesion and de-adhesion. S phase SMMC-7721 cells had higher adhesive forces than d phase cells [(307.65±92.10)×10-10N vs(195.42±60.72)×10-10N, P<0.01]. The expressive fluorescent intensity of integrinβ1 in G1 phase SMMC-7721 cells was depressed more significantly than the values of S phase and general SMMC-7721cells. The contribution of adhesive integrinβ1 was about 53% in this adhesive course. CONCLUSION: SMMC-7721 cells can be synchronized preferably in d and S phases with thymine-2-deoxyriboside and colchicines. The adhesive molecule integrinβ1 expresses a high level in SMMC-7721 cells and shows differences in various cell cycles, suggesting integrin β1 plays an important role in adhesion to endothelial cells. The change of adhesive forces in different cell cycle SMMC-7721 cells indicates that S phase cells play predominant roles possibly while they interact with endothelial cells.     

β3受体激动剂对心力衰竭大鼠β1、β2、β3肾上腺素能受体mRNA表达水平影响的实验研究

目的　研究 β3受体激动剂 (BRL 37344)对异丙肾上腺素诱导的心力衰竭 (心衰 )大鼠β1 、β2 、β3肾上腺素能受体 (β1 AR、β2 AR、β3AR)基因表达水平的影响 ,探讨 β1 AR、β2 AR、特别是 β3AR在心衰中的作用。方法　将大鼠随机分为对照组 (2 0只 )和心衰组 (90只 )。心衰组给予异丙肾上腺素 (isoproterenol,ISO)皮下注射 ,连续 2d。 1个月后 ,心衰组存活 40只大鼠 ,随机取存活大鼠 1 8只为ISO组 ,2 2只为BRL组。BRL组给予BRL 37344尾静脉注射 ,每周 2次。ISO组注射相应生理盐水。对照组不予处置 ,继续治疗 2～ 6周 ,分两个时段于 2周、6周检查以下指标 :(1 )左室舒张末压 (PED)、左室收缩末压 (PES)、左室压力最大上升速率 (dp/dtmax)、左室压力最大下降速度 (dp/dtmin)、左室等容舒张时间常数 (Tc) ,(2 )左室重量 /体重 ,(3)心肌组织 β1 AR、β2 AR、β3AR的mRNA水平 ,(4)死亡率。结果　 (1 )ISO组和BRL组较对照组PES、dp/dtmax、dp/dtmin绝对值明显减低 (均为P <0 0 1 ) ,而Tc、PED明显增高 (均为P <0 0 1 ) ;BRL组和ISO组比较 ,BRL组PES、dp/dtmax、dp/dtmin绝对值降低更明显 (P <0 0 5) ,Tc(P <0 0 5)、PED(P <0 0 1 )增高更明显。 (2 )左室重量 /体重 ,ISO组和BRL组较对照组明显增加 (     

Effect of β blockers on β_3-adrenoceptor mRNA Expression in the Rats with Chronic Heart Failure

Objectives To investigate the changes of β3-adrenoceptor (β3-AR) mRNA expression in the rats with chronic heart failure (CHF), and to explore the effect of β blockers (βBs) on β3 mRNA expression. Methods Thirty-four rats were randomly divided into Sham group (n = 10) and heart failure group (n = 24). Rat model was established by aortic constriction. The survival rats in heart failure group were divided into heart failure control group (HF group, n = 6), metoprolol group (MET group, n = 8) and carvedilol group (CAR group, n = 8) three months after operation. Metoprolol tartarte was started orally with 12 mg·kg-1·d-1, carvedilol with 6 mg·kg-1·d-1, isometric saline was started in HF group. After three months of drug therapy, measurement of hemodynamics, index of ventricular mass, the level of β3-AR mRNA expression were performed. Results Compared with Sham group, left ventricular end systolic pressure (LVESP), and the absolute values of maximal rate of rise and fall ( ± dp/dtmax) of left ventricular pressure were all significantly decreased (P < 0.01), left ventricular end diastolic pressure (LVEDP) was significantly increased in HF group (P < 0.01). The hemodynamic parameters were improved by βBs, and carvedilol was more effective than metoprolol (P < 0.01). The index of ventricular mass was higher in HF group than MET group, CAR group and Sham group (P < 0.01). βBs significantly decreased the index of left ventricular mass (LVMI), and Carvedilol was more effective than metoprolol (P < 0.01). The index of right ventricular mass (RVMI) did not change in MET group (P > 0.05), but significant decrease could be seen in CAR group (P < 0.01). The level of β3-AR expression in left ventricle was greater than that in right ventricle whether in the failing heart or in the non-failing heart. Compared with Sham group, the level of β3-AR mRNA expression was significantly increased in HF group (P < 0.01). The levels of β3-AR mRNA expression showed a remarkable decrease in CAR group(P < 0.01), but was not seen in MET group. Conclusions The β3-AR expression level remarkably increases in the rat's left and right failing ventricles. Carvedilol is more effective on improving hemodynamics and attenuating ventricular remodeling than metoprolol in the rats with CHF. Carvedilol rather than metoprolol downregulates β3-AR expression in the rat's failing ventricles. The beneficial effect of carvedilol in CHF maybe partly due to the downregulation of β3-AR expression in the failing heart.     

β3受体

β３受体［小田原雅人．内科，１９９６，７８（４）：７１９（日文）］儿茶酚胺是通过肾上腺素能α或β受体介导起作用的；但儿茶酚胺的β作用因组织而异，在脂肪细胞中是促进脂肪分解，即动员贮存于褐色和白色脂肪组织的中性脂肪酸；而且，在褐色脂肪组织中，通过腺粒体...     

Human β-defensin-3 induction in H pylori-infected gastric mucosal tissues

INTRODUCTION Defensins are antimicrobial peptide components of the innate immune system. Three subfamilies, α-defensins, β-defensins, and θ-defensins, distinguished according to structural features at the gene and protein levels, have been identified i…     

充满希望的第3代β阻滞剂:奈必洛尔

从β受体阻滞剂(βB)发展的历史来看,βB可以分为3代.第1代:非选择性βB,与β1或β2受体亲和力相同,如心得安、噻马洛尔、纳多洛尔.第2代:选择性β1受体阻滞剂:氨酰心安、倍他洛尔、比索心安、美托洛尔,但大剂量时也能阻断β2受体.     

β3肾上腺素能受体变异与肥胖及胰岛素抵抗的关系

本文综述了β３肾上腺素能受体的生物学特性及其与肥胖及胰岛素抵抗的关系。     

Prophylactic uses of integrin CD18-βA peptide in a murine polymicrobial peritonitis model

AIM:To evaluate the prophylactic properties of integrin CD18-βA peptide in a murine model of abdominal polymicrobial peritonitis and sepsis.METHODS:Bacterial sepsis was induced in Institute of Cancer Research(ICR) mice by cecal ligation and puncture(CLP) surgery.Inflicted mice were then injected with either sterile saline or CD18-βA peptide intraperitoneally at 2 h after surgery,and were sacrificed at 12 and 24 h after surgery.Blood samples were immediately collected,and analyzed for endotoxin activity and ...     

山东省汉族人β3肾上腺能受体基因多态性分析

应用多聚酶链反应限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）技术对２１２例山东省汉族人（非糖尿病６０例,２型糖尿病１３２例）进行β３肾上腺能受体（β３ＡＲ）基因Ｔｒｐ６４Ａｒｇ突变分析。结果表明,山东汉人β３ＡＲ Ｔｒｐ６４Ａｒｇ等位基因变异频率为１６％,２型糖尿病组与非糖尿病组β３ＡＲ Ｔｒｐ６４Ａｒｇ基因型和等位基因分布频率无显著差异（Ｐ〉０．０５）。提示山东省汉族人存在β３ＡＲ基因变异,但这种变     

肾上腺素β3受体基因多态性与肥胖、胰岛素抵抗及高血压

肾上腺素β1及β2 受体已经为人们所熟知 ,近年来关于肾上腺素 β3受体 (β3 adrenergicreceptor ,ADRβ3)的研究也越来越多。ADRβ3首先在大网膜和皮下脂肪组织中发现 ,1989年采用火鸡 β1 AR与人 β2 AR基因的完整编码区筛选人基因文库 ,得到ADRβ3基因克隆。随后对ADRβ3的药理学研究发现 ,ADRβ3的高选择性激动剂可作为抗肥胖和抗糖尿病的药物 ,进而在动物模型中证明ADRβ3与脂肪分解和生热作用相关。近年来对ADRβ3基因Trp6 4Arg多态性与肥胖、胰岛素抵抗、高血压的关系的研究有许多阳性发现。1　肾上腺素 β3受体的发现、…     

β3肾上腺素能受体基因与胰岛素抵抗研究进展

β肾上腺素能受体在脂肪分解和产热方面起着重要作用。由于其64位点基因存在多态性（Trp64Arg)，使细胞膜表面基因表达缺陷，细胞信号转导受损，从而影响脂肪组织的产热和分解，近年来多项研究显示β3肾上腺素能受体基因突变可造成胰岛素抵抗，临床表现如体重增加，且减轻体重困难，葡萄糖代谢率下降，早期出现2型糖尿病，另外还有血压，血脂的升高，月经初潮年龄提前等表现，此基因多态笥同样影响绝经后及妊娠期妇女的血糖和体重。     

ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population

AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping was performed for 15 single nucleotide polymorphisms(SNPs)in ITGA1.The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models.Multiple testing corrections were carried out following methodology for controlling the false discovery rate.Gene-based association tests were performed using the versatile gene-based association study(VEGAS)method.RESULTS:In the codominant model,the ORs for SNPs rs2432143(1.517;95%CI:1.144-2.011)and rs2447867(1.258;95%CI:1.051-1.505)were statistically significant.In the dominant model,polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors,with ORs of 1.337(95%CI:1.029-1.737)and 1.412(95%CI:1.061-1.881),respectively.In the recessive model,only the rs2432143 polymorphism was significant(OR=1.559,95%CI:1.150-2.114).The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model(OR=0.602,95%CI:0.212-0.709,P=0.021)and the dominant model(OR=0.653,95%CI:0.483-0.884).The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.In the dominant model,the A-T type of ITGA1 haplotype block 2 was a significant risk factor(OR=1.341,95%CI:1.034-1.741).SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and,thus,to the risk of developing gastric cancer.CONCLUSION:ITGA1 gene SNPs rs1862610,rs2432143,and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.     

Expression of E-selectin, integrinβ_1 and immunoglobulin superfamily member in human gastric carcinoma cells and its clinicopathologic significance

AIM: To study the expression levels of E- selectin, integrinβ1 and immunoglobulin supperfamily member-intercellular adhesion molecule-1 (ICAM-1) in human gastric carcinoma cells, and to explore the relationship between these three kinds of cell adhesion molecules and gastric carcinoma. METHODS: The serum contents of E-selectin, integrinβ1 and ICAM-1 were detected by enzyme-linked immuno-sorbent assay (ELISA), in 47 healthy individuals (control group) and in 57 patients with gastric carcinoma (gastric carcinoma group) respectively prior to operation and 7 d after operation. RESULTS: The serum E-selectin, ECAM-1 and integrinβ1 were found to be expressed in both control and gastric carcinoma groups. However, they were highly expressed in patients with gastric carcinoma patients before operation or with unresectable tumours. The expression levels of ICAM-1 and integrinβ1 were significantly higher in gastric carcinoma patients than in controls (P < 0.01). A comparison of the E-selectin levels between the two groups showed statistically insignificant differnce (P = 0.64). In addition, the expression levels were all decreased substantially in the postoperative patients subjected to radical resection of the tumours, indicating that the high level expressions of these compounds might be the important factor for predicting the prognosis of these patients. CONCLUSION: Serum E-selectin, ICAM-1 and integrin pi expression levels are probably related to the metastasis and relapse of gastric cancer.     

冠心病心绞痛患者血浆内啡肽水平与心功能的关系

目的探讨冠心病心绞痛患者β-内啡呔(β-EP)的血浆水平变化规律及其与心功能变化的关系及意义.方法观察42例冠心病心绞痛患者血浆β-EP水平和心功能指标的变化.结果不同临床心功能分组患者β-EP水平有明显差异,心衰Ⅱ～Ⅲ组β-EP水平高于心衰Ⅰ组,分别为218.5±65.2和138.5±44.6 pg/ml.不同β-EP水平分组患者心脏彩色多普勒心功能有明显差异,β-EP水平＞200pg/ml组患者的射血分数(EF)和心输出量(C())分别为0.47±0.20%和3.47±0.20l/min,β-EP水平＜100pg/ml组患者分别0.62±0.14%和5.62±0.14 l/min;组间比较差异显著.结论β-EP与心功能变化有相关性.β-EP水平过高是心衰的病理介质之一.β-EP监测是分析判断病情及预后的一项重要参考指标.     

NG-硝基-L-精氨酸甲基酯对心力衰竭大鼠应用β3受体激动剂后血流动力学和β受体mRNA表达水平的影响

目的研究不同剂量NG-硝基-L-精氨酸甲基酯(L-NAME)作用于心力衰竭(心衰)大鼠应用β3受体激动剂BRL37344(BRL)后的血流动力学、环-磷酸鸟苷(cGMP)含量和β受体mRNA表达水平,进一步明确β3受体在心衰中的作用途径和L-NAME的作用特点.方法将大鼠随机分为对照组(Ⅰ组)、异丙肾上腺素(Iso)组(Ⅱ组)、Iso+BRL组(Ⅲ组)、Iso+BRL+L-NAME低剂量组(5 mg/kg体重,Ⅳ组)、Iso+BRL+L-NAME中剂量组(50 mg/kg体重,Ⅴ组)、Iso+BRL+L-NAME高剂量组(100 mg/kg体重,Ⅵ组).测定 (1)血流动力学 左室舒张末压(LVEDP),左室收缩末压(LVESP),左室压力最大上升、下降速率(±dp/dt).(2)心肌cGMP含量.(3)心肌组织β1、β2、β3受体mRNA水平.结果①Ⅱ组较Ⅰ组±dp/dt绝对值、LVESP明显降低,LVEDP明显升高(除-dp/dt P< 0.05,余均为P< 0.01);Ⅲ组较Ⅱ组-dp/dt绝对值、LVESP明显下降,LVEDP明显升高(P< 0.05),+dp/dt变化呈下降趋势,但差异无统计学意义;随着L-NAME剂量的增加,±dp/dt绝对值升高,LVEDP降低,但大剂量L-NAME应用后,血流动力学又有恶化倾向. ②Ⅰ、Ⅱ、Ⅲ组cGMP水平呈逐渐上升趋势(均为P< 0.01),应用L-NAME后随着剂量的增加Ⅳ、Ⅴ、Ⅵ组cGMP呈下降趋势,大剂量应用L-NAME后cGMP回到正常对照组水平.③Ⅰ、Ⅱ、Ⅲ组比较,β1受体mRNA/β-actin mRNA为Ⅰ组最高、Ⅲ组最低,差异有统计学意义(均为P<0.01);β2受体mRNA/β-actin mRNA呈下降趋势,但三组间差异无统计学意义;而β3受体mRNA/β-actin mRNA的三组中Ⅲ组最高、Ⅰ组最低,差异有统计学意义(均为P<0.01);而Ⅳ、Ⅴ、Ⅵ组三种β受体mRNA水平与Ⅲ组相似,差异无统计学意义.结论β3受体经NOS途径发挥作用,L-NAME可部分阻断β3受体激动剂对衰竭心脏的负性肌力作用,改善心功能,但大剂量应用会加重心衰进程.     

原发性高血压人群胰岛素抵抗与β3—肾上腺素能受体基因多态性的关联

目的对中国汉族原发性高血压人群中胰岛素抵抗与β3-肾上腺素能受体(β3-AR)基因多态性的关系进行探讨.方法179名原发性高血压患者,以胰岛素敏感指数[IAI=-ln(空腹血糖×空腹血胰岛素)]50百分位点将此人群划分为胰岛素相对抵抗组(IAI≤-4.88)及胰岛素相对敏感组(IAI＞-4.88),并以42名正常人作为对照.测定血压、空腹血糖、空腹血胰岛素、血脂、尿酸等指标,并提取DNA进行β3-AR基因64位T/A多态性的分析.结果β3-AR基因64位Trp→Arg突变携带者的频率在抵抗组较敏感组高(28.0%vs15.7%,P＜0.05).Spearman相关分析发现β3-AR基因型与IAI呈负相关,与血清甘油三酯、总胆固醇、尿酸水平正相关(P＜0.05).运用Logistic回归分析,总人群中β3-AR基因突变型与胰岛素抵抗显著相关,相对危险度为2.36(95%可信限1.10～5.06,P＜0.05).结论原发性高血压人群中β3-AR基因64Arg突变携带者易发生胰岛素抵抗,此突变与高甘油三酯、高胆固醇、高尿酸血症相关.β3-AR基因64位Trp→Arg突变可能是部分高血压患者胰岛素抵抗的遗传基础.     

整合素β1在肝泡型包虫病患者肝脏中的表达及其与临床病理特征的相关性北大核心CSCD

目的检测肝泡型包虫病(AE)患者肝组织中整合素β1(Integrinβ1)的表达水平,并探讨其与患者临床病理特征的相关性。方法取73例AE患者肝脏组织样品及8例正常肝脏样品做石蜡组织切片,采用免疫组织化学染色法检测Integrinβ1的表达情况,分析Integrinβ1的表达水平与Child-pugh分级、PNM分型、血管新生等临床病理特征的相关性。结果AE患者病灶近旁及远端肝组织integrinβ1表达显著高于正常肝组织(P<0.01)。相关性分析显示Integrinβ1表达与AE患者PNM分型及新生血管数(Integrinβ1高表达组23.7±10.78,低表达组16.09±7.35)呈正相关(P<0.05),且随着AE病灶范围(P分期)的加重,Integrinβ1呈高表达(P1,0%;P2,13.6%;P3,75.0%;P4,50%)(P<0.01),而与患者年龄、性别、Child-Pugh分级等无显著相关性(均P>0.05)。结论肝泡型包虫病患者的肝组织高表达Integrinβ1,提示Integrinβ1可能参与AE病灶浸润过程,为阐明AE的致病机制和寻找新的药物靶标奠定了基础。