目的研究替米沙坦促进大鼠胰岛素分泌作用相关的信号通路。方法(1)分离成年Wistar大鼠胰腺获得胰岛和胰岛细胞,通过胰岛素分泌实验观察药物对胰岛素分泌的影响,通过钙成像实验和全细胞膜片钳技术观察药物对β细胞内Ca^(2+)浓度的变化和...目的研究替米沙坦促进大鼠胰岛素分泌作用相关的信号通路。方法(1)分离成年Wistar大鼠胰腺获得胰岛和胰岛细胞,通过胰岛素分泌实验观察药物对胰岛素分泌的影响,通过钙成像实验和全细胞膜片钳技术观察药物对β细胞内Ca^(2+)浓度的变化和对离子通道的作用。(2)使用过表达电压门控性钾(voltage-gated potassium channel,Kv)通道2.1亚型(Kv2.1)的慢病毒转染中国仓鼠卵巢(Chinese hamster ovary,CHO)细胞构建CHO-Kv2.1细胞系,使用膜片钳技术观察替米沙坦对Kv2.1通道的直接作用。结果缬沙坦和厄贝沙坦无类似替米沙坦的高糖浓度下促胰岛素分泌、升高β细胞内Ca^(2+)浓度和抑制β细胞的Kv通道等作用。过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)阻断剂GW9662亦未阻断替米沙坦的上述作用。而替米沙坦可以浓度依赖性地抑制CHO-Kv2.1细胞的Kv2.1通道电流。结论替米沙坦的促胰岛素分泌作用可能与血管紧张素Ⅱ-1型(angiotensin II type 1,AT-1)受体和PPARγ无关,但至少与对Kv2.1通道的直接抑制作用有关。展开更多
An as-cast magnesium alloy with high Al content Mg15Al was subjected to equal-channel angular pressing （ECAP） through a die with an angle of φ= 90？ at 553 K following route Bc. It is found that the network β-Mg17...An as-cast magnesium alloy with high Al content Mg15Al was subjected to equal-channel angular pressing （ECAP） through a die with an angle of φ= 90？ at 553 K following route Bc. It is found that the network β-Mg17Al12 phases in the as-cast Mg15Al alloy are broken into small blocks and dispersed uniformly with increasing numbers of pressing passes. Moreover, many nano-sized Mg17Al12 particles precipitate in the ultra-fine α-Mg matrix. The grains are obviously refined. However, the grain structure is inhomogeneous in different areas of the alloy. The average size of the primary phase α-Mg is reduced to about 1 μm while grains of around 0.1-0.2 μm are obtained in some two-phase areas. With additional ECAP passes （up to 8）, coarsening of the grains occurs by dynamic recovery. Room temperature tensile tests show that the mechanical properties of Mg15Al alloys are markedly improved after 4 ECAP passes. The ultimate tensile strength and elongation to failure increase from 150 MPa to 269.3 MPa and from 0.05% to 7.4%, respectively. Compared with that after 4 passes, the elongation to failure of the alloy increases but the strength of the alloy slightly decreases after 8 ECAP passes. Fracture morphology of the ECAP-processed alloy exhibits dimple-like fracture characteristics while the as-cast alloy shows quasi-cleavage fractures.展开更多
目的:研究Hp(Helicobacter pylori,Hp)感染在胃癌发生发展中的作用。方法:运用实时定量PCR法检测氯离子通道蛋白基因(Chloride ion channel protein,CICP)及β-肌动蛋白基因在50例人胃癌组织的表达,并分析其表达与临床病理特征和胃癌组...目的:研究Hp(Helicobacter pylori,Hp)感染在胃癌发生发展中的作用。方法:运用实时定量PCR法检测氯离子通道蛋白基因(Chloride ion channel protein,CICP)及β-肌动蛋白基因在50例人胃癌组织的表达,并分析其表达与临床病理特征和胃癌组织中Hp感染状态的关系。结果:两个基因在人胃癌组织及淋巴结组织的表达显著高于癌旁组织(P<0.05)。氯离子通道蛋白基因的表达与胃癌患者pTNM分期及患者生存期相关(P<0.05),而β-肌动蛋白基因的表达与pTNM分期及淋巴结转移相关(P<0.05);人胃癌组织中Hp的感染与氯离子通道蛋白及β-肌动蛋白基因的表达上调相关(P<0.05)。结论:Hp的感染可以上调胃癌组织中氯离子通道蛋白及β-肌动蛋白基因的表达,检测这两个基因的表达对预测胃癌患者的预后有一定作用。展开更多
文摘目的研究替米沙坦促进大鼠胰岛素分泌作用相关的信号通路。方法(1)分离成年Wistar大鼠胰腺获得胰岛和胰岛细胞,通过胰岛素分泌实验观察药物对胰岛素分泌的影响,通过钙成像实验和全细胞膜片钳技术观察药物对β细胞内Ca^(2+)浓度的变化和对离子通道的作用。(2)使用过表达电压门控性钾(voltage-gated potassium channel,Kv)通道2.1亚型(Kv2.1)的慢病毒转染中国仓鼠卵巢(Chinese hamster ovary,CHO)细胞构建CHO-Kv2.1细胞系,使用膜片钳技术观察替米沙坦对Kv2.1通道的直接作用。结果缬沙坦和厄贝沙坦无类似替米沙坦的高糖浓度下促胰岛素分泌、升高β细胞内Ca^(2+)浓度和抑制β细胞的Kv通道等作用。过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)阻断剂GW9662亦未阻断替米沙坦的上述作用。而替米沙坦可以浓度依赖性地抑制CHO-Kv2.1细胞的Kv2.1通道电流。结论替米沙坦的促胰岛素分泌作用可能与血管紧张素Ⅱ-1型(angiotensin II type 1,AT-1)受体和PPARγ无关,但至少与对Kv2.1通道的直接抑制作用有关。
基金Funded by the Taiyuan Special Fund for Sci-Tech Star (No. 09121002)the Youth Science Foundation of Shanxi Province (No.2008021033)Shanxi Research Fund for Returned Scholars (No.2007-25)
文摘An as-cast magnesium alloy with high Al content Mg15Al was subjected to equal-channel angular pressing （ECAP） through a die with an angle of φ= 90？ at 553 K following route Bc. It is found that the network β-Mg17Al12 phases in the as-cast Mg15Al alloy are broken into small blocks and dispersed uniformly with increasing numbers of pressing passes. Moreover, many nano-sized Mg17Al12 particles precipitate in the ultra-fine α-Mg matrix. The grains are obviously refined. However, the grain structure is inhomogeneous in different areas of the alloy. The average size of the primary phase α-Mg is reduced to about 1 μm while grains of around 0.1-0.2 μm are obtained in some two-phase areas. With additional ECAP passes （up to 8）, coarsening of the grains occurs by dynamic recovery. Room temperature tensile tests show that the mechanical properties of Mg15Al alloys are markedly improved after 4 ECAP passes. The ultimate tensile strength and elongation to failure increase from 150 MPa to 269.3 MPa and from 0.05% to 7.4%, respectively. Compared with that after 4 passes, the elongation to failure of the alloy increases but the strength of the alloy slightly decreases after 8 ECAP passes. Fracture morphology of the ECAP-processed alloy exhibits dimple-like fracture characteristics while the as-cast alloy shows quasi-cleavage fractures.
文摘目的筛选针对Orai1分子第1膜外区蛋白的核酸适配体,探讨适配体通过拮抗钙离子释放激活通道(Ca2+release activation channel,CRAC)抑制肥大细胞活化的效应。方法构建随机单链DNA文库,利用不对称PCR对单链DNA文库进行扩增。采用聚苯乙烯酶联板为介质的指数富集配体系统进化(systematic evolution of ligand by exponential enrichment,SELEX)技术筛选核酸适配体。利用酶联免疫吸附实验检测各轮筛选序列与靶蛋白的亲和力,验证适配体与靶蛋白的特异性结合;激光共聚焦显微镜观察适配体对细胞内钙离子浓度变化的影响;利用IgE介导的肥大细胞脱颗粒模型,观察适配体对β-氨基己糖苷酶释放的抑制效应。结果经过12轮SELEX筛选,获得了7条核酸适配体,其中AptamerY1解离常数(Kd值)为1.72×10-8mol/L。以终浓度2μg/mL的AptamerY1可抑制由IgE介导的人肥大细胞系LAD2钙离子内流,并对LAD2细胞的β-氨基己糖苷酶释放抑制率达95%。结论通过SELEX筛选,获得了7条针对Orai1分子第1膜外区的核酸适配体,所获得适配体可对肥大细胞LAD2钙内流有效抑制,进而抑制肥大细胞活化和β-氨基己糖苷酶的释放。
文摘目的:研究Hp(Helicobacter pylori,Hp)感染在胃癌发生发展中的作用。方法:运用实时定量PCR法检测氯离子通道蛋白基因(Chloride ion channel protein,CICP)及β-肌动蛋白基因在50例人胃癌组织的表达,并分析其表达与临床病理特征和胃癌组织中Hp感染状态的关系。结果:两个基因在人胃癌组织及淋巴结组织的表达显著高于癌旁组织(P<0.05)。氯离子通道蛋白基因的表达与胃癌患者pTNM分期及患者生存期相关(P<0.05),而β-肌动蛋白基因的表达与pTNM分期及淋巴结转移相关(P<0.05);人胃癌组织中Hp的感染与氯离子通道蛋白及β-肌动蛋白基因的表达上调相关(P<0.05)。结论:Hp的感染可以上调胃癌组织中氯离子通道蛋白及β-肌动蛋白基因的表达,检测这两个基因的表达对预测胃癌患者的预后有一定作用。
