抗抑郁药万拉法新的神经保护作用

目的：探讨万拉法新的神经保护作用及其机制。 方法：采用体外原代培养的大鼠海马神经元,复制谷氨酸损伤模型以模拟抑郁症时的病理改变,在体外通过MTT法检测万拉法新对神经元存活率的影响,并且测定万拉法新应用前后LDH的释放、GSH水平、MDA含量和SOD活性的改变情况。 结果：万拉法新抵抗了谷氨酸诱导的神经元损伤,提高了神经元存活率,减少了LDH的释放,维持细胞膜的完整性,提高了神经细胞内SOD活性和GSH水平,降低了MDA含量。 结论：万拉法新具有神经保护作用。     

人肝再生增强因子CXXC结构域与生物学活性的关系

目的：初步探讨人肝再生增强因子蛋白 (human augmenter of liver regeneration protein, hALRp) CXXC结构域与生物学活性的关系。方法：根据酶催化反应中巯基浓度的变化,测定目的蛋白巯基氧化酶活性;采用GST-pulldown方法测定目的蛋白与GST-Na⁺,K⁺-ATPase融和蛋白体外相互作用;用MTT法检测目的蛋白促进成人肝细胞HL-7702增殖情况;探讨hALR与hALR-C65A(hALRp的CXXC结构域突变)蛋白活性差异。结果： 在巯基氧化酶活性实验中,酶活性以转换数 (TN) 表示,hALR组TN=1.25±0.21,而hALR-C65A组TN=0,与 hALR组比较差异有显著性 (P<0.05)。但hALR-C65A与GST-Na⁺,K⁺-ATPase融和 蛋白体外相互作用和促进肝细胞增殖活性与hALRp比较无明显变化。 结论：hALRp的CXXC结构在巯基氧化 酶活性方面有重要作用,但该结构改变并不影响hALRp与Na⁺,K⁺-ATPase的相互作用和促进肝细胞增殖活性。     

低剂量辐射诱导免疫适应性反应的实验研究

目的　研究低剂量辐射能否诱导免疫适应性应。方法　３ＨＴｄＲ 掺入法检测淋巴细胞增殖率;ＣＴＬＬ依赖株检测ＩＬ２ 活性;单克隆抗体免疫荧光标记,流式细胞术（ＦＣＭ） 检测淋巴细胞亚组及膜受体表达;ＰＩ标记,ＦＣＭ 检测细胞周期及细胞凋亡;双抗体夹心间接ＥＬＩＳＡ 法测定可溶性白介素２ 受体;Ｆｕｒａ２ 负载,双波长荧光测定法检测细胞内［Ｃａ２＋ ］ｉ;传代培养细胞测定细胞倍增时间。结果　低剂量辐射预照射可明显减轻其后大剂量照射对诸多淋巴细胞功能的抑制作用。结论　低剂量Ｘ 射线可诱导多参数免疫适应性反应。     

Increase in efficacy of cancer radiotherapy by combination with whole-body low dose irradiation

Purpose:Design of cancer radiotherapy protocol to reduce radiation dose and increase treatment efficacy in Lewis lung cancer (LLC) model.

Methods: C57BL/6J mice subcutaneously implanted with LLC were treated by conventional radiotherapy (2Gy × 6) combined with LDWBI (low dose whole-body irradiation; the second, third, fifth and sixth local doses of 2Gy each substituted by LDWBI with 0.075Gy) and/or gene therapy (intratumor injection of pEgr-IL-18-B7.1 plasmid 24 h before the first and fourth local doses). Immunologic mechanisms were explored.

Results: Cancer control was most significantly improved in the group receiving local radiotherapy combined with LDWBI and gene therapy as shown by prolongation of mean survival time by 60.4%, reduction in average tumor weight by 70.8%, decrease in pulmonary metastasis by 66.9% and decrease in intratumor angiogenesis by 64.8% as compared to local radiotherapy alone (p < 0.05). These changes in tumor growth and progression were accompanied with up-regulation of host immunity manifested by stimulated NK (natural killer) and CTL (cytotoxic T lymphocyte) activity, IFN (interferon)-gamma and TNF (tumor necrosis factor)-alpha secretion, PKC (protein kinase C)-theta activation and LAMP (lysosomal associated membrane protein)-1 expression.

Conclusion: Combination of conventional radiotherapy with LDWBI and gene transfer could reduce total radiation dose by 2/3 and at the same time improve treatment efficacy of cancer accompanied with up-regulated host anticancer immunity.     

Genetic and functional study of the IPO5 gene in schizophrenia

The present work reported on a weak association of the importin 5 (IPO5) gene with schizophrenia in combined family and case-control samples and also investigated a possible mechanism by which the IPO5 gene may contribute to the development of the disease in a Chinese population. Our results suggest that abnormal expression and alternative splicing of the IPO5 gene may be involved in the pathophysiology of schizophrenia.     

N-乙酰半胱氨酸对糖尿病大鼠脾细胞凋亡及免疫相关因子的干预作用

目的：观察N-乙酰半胱氨酸（NAC）对糖尿病（DM）大鼠脾细胞凋亡和免疫因子的影响,为NAC在糖尿病并发症预防及糖尿病的治疗方面提供理论依据。方法：实验分为对照组、DM组和NAC+DM组,链脲佐菌素腹腔注射诱导DM大鼠模型,灌胃给予NAC,于给药结束4周末断头处死,分别采用Annexin V/碘化丙啶（PI）双荧光标记、PI单标记和PE标记TCRαβ抗体标记,流式细胞术检测脾细胞凋亡、细胞周期及TCRαβ百分数变化;ELISA法检测血清和脾细胞培养上清IL-2含量的变化。结果：与对照组比较,DM组大鼠脾细胞凋亡率、TCRαβ百分数及血清IL-2含量、G₀/G₁期和G₂/M期脾细胞数明显升高（P<0.05或P<0.001）,S期脾细胞数和培养上清IL-2含量明显降低（P<0.05或P<0.001）;DM+NAC组脾细胞凋亡率有所下降,与对照组比较差异无显著性,且细胞周期各期细胞数无明显变化。与DM组比较,DM+NAC组脾细胞凋亡率、TCRαβ百分数、血清IL-2含量、G₀/G₁期和G₂/M期脾细胞数明显降低（P<0.05或P<0.001）,S期脾细胞数和培养上清IL-2含量明显升高（P<0.05）。结论：NAC能降低DM所致的脾细胞凋亡增加,可纠正DM引发的脾细胞周期阻滞,调节DM所致的免疫因子失衡。     

低剂量电离辐射诱导小鼠睾丸生精细胞线粒体结构、ATPase 活性及钙离子浓度的变化

目的：观察0.025~0.200 Gy X线低剂量电离辐射后3~24 h小鼠生精细胞线粒体结构、睾丸组织内ATPase和生精细胞钙离子浓度的变化,阐明线粒体结构与相关生物学功能改变在调控凋亡中的作用。方法：透射电镜检测小鼠睾丸生精细胞线粒体结构的改变;蛋白酶法检测ATPase活性的改变;以Fluo-3为探针,流式细胞术检测钙离子浓度（［Ca²⁺］i）的变化。结果：0.075 Gy照射后12 h,小鼠精原细胞与精母细胞线粒体肿胀、空泡化、嵴断裂;精子细胞核固缩,顶体囊泡结构模糊,核膜结构不清楚,线粒体空泡化。0.025~0.200 Gy照射后12 h,睾丸组织中Na⁺-K⁺-ATPase活性较0 Gy照射降低,其中0.050~0.200 Gy较0 Gy显著降低（P< 0.05）,Ca²⁺-ATPase活性均较0 Gy照射显著降低（P< 0.05）;生精细胞中［Ca²⁺］i也具有同样的剂量-效应关系,其中0.075 Gy照射后,较0 Gy显著降低（P< 0.05）。0.075 Gy照射后3~24 h,睾丸组织中Na⁺-K⁺-ATPase活性较0 h均显著降低（P< 0.05）;Ca²⁺-ATPase活性在3 h稍有升高后,6~24 h较0 h均显著降低（P< 0.05）;生精细胞中［Ca²⁺］i也具有相似的时程-效应关系。结论：低剂量电离辐射能够诱导小鼠睾丸生精细胞线粒体结构的改变;同时,其诱导ATPase活性和［Ca²⁺］i的变化具有剂量-效应与时程-效应规律性。     

A study of circulating gliadin antibodies in schizophrenia among a Chinese population

The present work measured circulating antibodies against native gliadins, deamidated gliadin-derived epitopes, and transglutaminase 2 (TGM2) in 473 patients with schizophrenia and 478 control subjects among a Chinese population. The results showed that 27.1% of patients with schizophrenia were positive for the IgA antibody against native gliadins compared with 17.8% of control subjects (χ(2) = 11.52, P = .0007, OR = 1.72, 95% CI 1.25-2.35), although this significant difference appeared to be due mainly to low IgA gliadin antibody levels in female controls. A total of 27.6% of female patients were positive for IgA gliadin antibodies compared with 13.9% of female controls (χ(2) = 10.46, P = .0012, OR = 2.36, 95% CI 1.39-4.01), and 26.4% of male patients were positive for IgA antibodies compared with 19.8% of male controls (χ(2) = 3.26, P = .071, OR = 1.46, 95% CI 0.97-2.19). Of 128 patients who were positive for the IgA antibody against native gliadins, 8 were positive for the IgA antibody against deamidated gliadin epitopes and 1 was positive for IgA anti-TGM2 antibody. However, quantitative analysis demonstrated that the mean levels of IgA antibodies against deamidated gliadin epitopes and TGM2 were significantly lower in patients with schizophrenia than the control subjects (P < .001 and P = .008, respectively). The prevalence of IgG antibodies against native gliadins was not significantly different between the patient group and the control group (χ(2) = 2.25, P = .134, OR = 1.32, 95% CI 0.92-1.88). This study suggests that specific gliadin-derived epitopes may be involved in schizophrenia.     

电离辐射对小鼠EL-4淋巴瘤细胞P21蛋白表达的影响

目的阐明电离辐射对小鼠EL-4淋巴瘤细胞P21蛋白表达的影响。方法采用免疫细胞化学方法和流式细胞术检测X射线照射对P21蛋白表达的时程和量效变化的影响。结果时程实验结果显示，离体培养的EL-4细胞经4．0Gy X射线照射后，P21蛋白表达在2．72h（免疫细胞化学方法检测）和8—72h（流式细胞术检测）明显增高（分别为P〈0．01、P〈0．001）。量效实验结果显示，X射线照射后24h，P21蛋白表达在0．5—6．0Gy（免疫细胞化学方法检测）和1．0～4．0Gy（流式细胞术检测）明显增高（分别为P〈0．05、P〈0．01、P〈0．001）。结论X射线能诱导P21蛋白表达增高，在一定范围内存在时间和剂量依赖关系。