已报道低浓度溶血磷脂酸(lysophosphatidic acid,LPA)对去血清培养所致的神经元凋亡有神经保护作用.为了进一步观察LPA是否对β-amyloid peptide fragment 31-35(AβP31-35)所致的神经元凋亡也起类似的作用,本研究应用DNA电泳分析、HO33...已报道低浓度溶血磷脂酸(lysophosphatidic acid,LPA)对去血清培养所致的神经元凋亡有神经保护作用.为了进一步观察LPA是否对β-amyloid peptide fragment 31-35(AβP31-35)所致的神经元凋亡也起类似的作用,本研究应用DNA电泳分析、HO33342和TUNEL染色法等技术,对培养的小鼠大脑皮层神经元进行了观察.结果显示,只有使用较低浓度的LPA(1~10μmol/L)、并且将此剂量的LPA比AβP31-35提前12~24 h加入培养液时,才可看到LPA明显削弱了AβP31-35所致的神经元凋亡.以上结果表明,适当浓度的LPA在长时间预作用的条件下,可对AβP31-35所致的皮层神经元凋亡起保护因子或抗凋亡因子的作用,但其作用途径可能较在去血清培养所致的凋亡时更为复杂,因为在去血清的同时加入LPA就能制止去血清所致的凋亡.展开更多
Background We previously reported that iodine-131(131^I)-Iabeled anti-pro-gastrin-releasing peptide (ProGRP(31-98)) monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing s...Background We previously reported that iodine-131(131^I)-Iabeled anti-pro-gastrin-releasing peptide (ProGRP(31-98)) monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing small cell lung cancer (SCLC) xenografts. However, 1311-D-D3 was cleared slowly from the body, and the best radioimmunoimaging time for SCLC was 72-96 hours after injection. The aims of this study were to radiolabel anti-ProGRP(31-98) D-D3 monoclonal antibody with technetium-99m(99m^Tc) and to investigate the biodistribution of this antibody in healthy ICR mice. Methods D-D3was labeled with 99m^Tc via the 2-mercaptoethanol reduction method. 99m^Tc-D-g3 was purified by the gel column separation method. The labeling efficiency and radiochemical purity were measured by thin-layer chromatography. The immunological activity of 99m^Tc-D-O3 was determined with cell conjugation assays. 99m^Tc-D-D3 was injected into healthy ICR mice via a tail vein, and all the healthy ICR mice were sacrificed by cervical dislocation at a designated time. Then, the blood and major organs were removed and weighed, and counted in a gamma scintillation counter to determine the percentage of the injected dose per gram (%ID/g). Results The labeling rate and the radiochemical purity of 99m^TC-D-D3 were (73.87±2.89)% and (94.13±4.49)%, respectively. The immunobinding rates of 99m^Tc-O-D3 to the human small cell lung cancer NCI-H446 cell line and lung adenocarcinoma A549 cell line were (81.2±2.37)% and (24.3±1.46)%, respectively. The distribution data of normal ICR mice demonstrated that 99m^TC-D-D3was mainly distributed in the liver, kidney and lung, and less in the brain tissue and muscle. Conclusions 99m^Tc-D-D3 antibody not only had high radiochemical purity, but also had good stability both in vitro and in vivo, and maintained good immunological activity. 99m^Tc-D-D3 was metabolized mainly in the kidney and liver, and the blood radioactivity decreased rapidly. Thus, 99m^Tc-O-D3 is conducive to the radioimmunoimaging of SCLC.展开更多
文摘Background We previously reported that iodine-131(131^I)-Iabeled anti-pro-gastrin-releasing peptide (ProGRP(31-98)) monoclonal antibody D-D3 could selectively accumulate in the tumor sites of nude mice bearing small cell lung cancer (SCLC) xenografts. However, 1311-D-D3 was cleared slowly from the body, and the best radioimmunoimaging time for SCLC was 72-96 hours after injection. The aims of this study were to radiolabel anti-ProGRP(31-98) D-D3 monoclonal antibody with technetium-99m(99m^Tc) and to investigate the biodistribution of this antibody in healthy ICR mice. Methods D-D3was labeled with 99m^Tc via the 2-mercaptoethanol reduction method. 99m^Tc-D-g3 was purified by the gel column separation method. The labeling efficiency and radiochemical purity were measured by thin-layer chromatography. The immunological activity of 99m^Tc-D-O3 was determined with cell conjugation assays. 99m^Tc-D-D3 was injected into healthy ICR mice via a tail vein, and all the healthy ICR mice were sacrificed by cervical dislocation at a designated time. Then, the blood and major organs were removed and weighed, and counted in a gamma scintillation counter to determine the percentage of the injected dose per gram (%ID/g). Results The labeling rate and the radiochemical purity of 99m^TC-D-D3 were (73.87±2.89)% and (94.13±4.49)%, respectively. The immunobinding rates of 99m^Tc-O-D3 to the human small cell lung cancer NCI-H446 cell line and lung adenocarcinoma A549 cell line were (81.2±2.37)% and (24.3±1.46)%, respectively. The distribution data of normal ICR mice demonstrated that 99m^TC-D-D3was mainly distributed in the liver, kidney and lung, and less in the brain tissue and muscle. Conclusions 99m^Tc-D-D3 antibody not only had high radiochemical purity, but also had good stability both in vitro and in vivo, and maintained good immunological activity. 99m^Tc-D-D3 was metabolized mainly in the kidney and liver, and the blood radioactivity decreased rapidly. Thus, 99m^Tc-O-D3 is conducive to the radioimmunoimaging of SCLC.