GSTM1、GSTT1基因缺失与肺癌易感性的关系

目的探讨谷胱苷肽S转移酶M1（GSTM1）、谷胱苷肽S转移酶T1（GSTT1）基因缺失与肺癌发病之间的关系及其与P16表达降低的相关性在肺癌发生中的作用。方法采用PCR技术检测77例肺癌患者和107例健康对照人群中GSTM1、GSTT1基因缺失的频率，以十二烷基磺酸钠（SDS）-聚丙烯酰胺凝胶电泳及蛋白印迹（WeStern—blot）技术测定P16蛋白在正常组织中的表达。结果病例组GSTM1基因缺失频率为58．4％，显著高于对照组缺失频率为42．1％（X^2=4．811，P=0．028），危险度分析OR=1．938，95％CI=1．070～3．509；病例组GSTT1基因缺失频率为57．1％，接近对照组50．5％缺失频率的水平（X^2=0．802，P=0．371）。联合分析表明，2种基因在肺癌发生中具有协同作用。GSTM1空白基因型与GSTM1非空白基因型个体相比、GSTM1／GSTT1联合空白基因型与其他联合多态基因型相比P16表达水平降低，差异有统计学意义（P〈0．05）。结论GSTM1基因缺失或GSTM1、GSTT1基因联合缺失在肺癌患者中发生频率增高，可增加个体患肺癌的易感性；GSTM1基因缺失及GSTM1／GSTT1联合缺失可能与抑癌基因p16的蛋白表达减低有关。     

广东汉族人群谷胱甘肽硫转移酶A1基因多态性

目的探讨广东健康汉族人群谷胱甘肽硫转移酶A1（hGSTA1）基因多态性的分布。方法采用聚合酶链反应-限制性片段长度多态性方法（PCR-RFLP）检测217名广东健康汉族人hGSTA1基因型。结果GSTA1基因野生型纯合子（GSTA1＊A／＊A）分布频率为76．0％（165／217），突变型纯合子（GSTA1＊B／＊B）为2．8％（6／217），突变型杂合子（GSTA1＊A／＊B）为21．2％（46／217）；GSTA1基因多态性的性别分布差异无统计学意义（P〉0．05）。结论广东健康汉族人群GSTA1基因多态性分布与日本人相似，但与美国白人、美国黑人存在差异。     

还原型谷胱甘肽联合二甲双胍治疗2型糖尿病并发脂肪肝疗效观察

①目的探讨还原型谷胱甘肽(GSH)联合二甲双胍(m etform in)治疗糖尿病并发脂肪肝的疗效。②方法48例糖尿病并发脂肪肝患者,均在运动与饮食治疗基础上,常规护肝治疗;用还原型谷胱甘肽1 200mg,加入5%葡萄糖注射液250mL中,每日1次,静脉滴注,每次口服二甲双胍片0.25g,每日3次。3个月为一疗程,观察有关指标及B超影像学改变。③结果经治疗后患者丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、谷氨酰转肽酶(GGT)降至正常(P<0.001),血总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及体重指数(BM I)值较治疗前显著降低(P<0.001),空腹血糖(FPG)、糖化血红蛋白(HbA1 c)较治疗前下降(P<0.001),计算比较稳态模式胰岛素抵抗指数(HOMA-IR)和稳态模式胰岛素敏感指数(HOMA-IAI)值,差异具有显著性意义(P<0.005)。④结论对伴有脂肪肝的2型糖尿病患者应用还原型谷胱甘肽联合二甲双胍治疗,能有效地改善胰岛素抵抗,提高胰岛素敏感性,具有降酶、降糖、调脂的功效,疗效较好。     

谷胱甘肽对人离体嗜中性白细胞超氧阴离子产生和清除的影响

目的：研究谷胱甘肽（GSH）对人离体嗜中性白细胞超氧阴离子产生和清除的影响及机制。方法：用细胞色素C还原法测定3种刺激剂：N-甲酰甲硫氨酰-亮氨酰-苯丙氨酸（fMLP）、佛波豆蔻醚乙酸盐（PMA）和花生四烯酸（AA）介导的嗜中性白细胞超氧阴离子释放量。用Western blot法检测嗜中性白细胞蛋白质因子p47^phox磷酸化。结果：GSH呈浓度依赖性促进fMLP介导的嗜中性白细胞释放超氧阴离子，不影响PMA和AA介导的嗜中性白细胞释放超氧阴离子。酪氨酸激酶抑制剂5，7，45-三羟基异黄酮明显抑制fMLP介导的氧自由基产生，而蛋白激酶C抑制剂十字孢碱仅有轻度抑制作用。在非初始化的嗜中性白细胞GSH可清除fMLP、PMA和AA诱导产生的超氧阴离子。GSH刺激fMLP介导的嗜中性白细胞质因子p47如磷酸化，与其对超氧阴离子释放的影响一致。结论：GSH对刺激剂介导的超氧阴离子的产生依赖于膜受体的激活和还原型辅酶Ⅱ（NADPH）氧化酶p47^phox磷酸化。     

Gene expression of antioxidant enzymes in experimental diabetic neuropathy

Chronic hyperglycemia results in a large deficit in nerve blood flow. Both autoxidative- and ischemia-induced lipid peroxidation occurs, with resultant peripheral sensory neuropathy in streptozotocin-induced diabetes in the rat. Free radical defenses, especially involving antioxidant enzymes, have been suggested to be reduced, but scant information is available on chronic hyperglycemia. We evaluated the gene expression of glutathione peroxidase, catalase, and superoxide dismutase (cuprozinc and manganese separately) in L4,5 dorsal root ganglion (DRG) and superior cervical ganglion, as well as enzyme activity of glutathione peroxidase in DRG and sciatic nerve in experimental diabetic neuropathy of 3 months and 12 months durations. We also evaluated nerve electrophysiology of caudal, sciatic-tibial, and digital nerves. A nerve conduction deficit was seen in all nerves in experimental diabetic neuropathy at both 3 and 12 months. Gene expression of glutathione peroxidase, catalase, cuprozinc superoxide dismutase, and manganese superoxide dismutase were not reduced in experimental diabetic neuropathy at either 3 or 12 months. Catalase mRNA was significantly increased in experimental diabetic neuropathy at 12 months. Glutathione peroxidase enzyme activity was normal in sciatic nerve. We conclude that gene expression is not reduced in peripheral nerve tissues in very chronic experimental diabetic neuropathy. Changes in enzyme activity may be related to duration of diabetes or due to post-translational modifications.     

Exposure of brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation.

Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m3) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m3), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4+ and CD8+ subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.     

Propylene oxide in blood and soluble nonprotein thiols in nasal mucosa and other tissues of male Fischer 344/N rats exposed to propylene oxide vapors--relevance of glutathione depletion for propylene oxide-induced rat nasal tumors.

High concentrations of propylene oxide (PO) induced inflammation in the respiratory nasal mucosa (RNM) of rodents. Concentrations > or =300 ppm caused nasal tumors. In order to investigate if glutathione depletion could be relevant for these effects, we determined in PO exposed male Fischer 344/N rats PO in blood and soluble nonprotein SH-groups (NPSH) in RNM and other tissues. Rats were exposed once (6 h) to PO concentrations between 0 and 750 ppm, and repeatedly for up to 20 days (6 h, 5 days/week) to concentrations between 0 and 500 ppm. At the end of the exposures, PO in blood and NPSH in tissues were determined. PO in blood was dependent on concentration and duration of exposure. After the 1-day exposures, NPSH depletion was most distinctive (RNM > liver > lung). Compared to controls, NPSH levels were 43% at 50 ppm PO in RNM and 16% at > or =300 ppm in both RNM and liver. Lung NPSH fell linearly to 20% at 750 ppm. After repeated exposures over 3 and 20 days to 5, 25, 50, 300, and 500 ppm, NPSH losses were less pronounced. At both time points, NPSH were 90%, 70%, 50%, 30%, and 30% of the control values in RNM. Liver NPSH decreased to 80% and 50% at 300 and 500 ppm, respectively. After 20 days, lung NPSH declined to 70% (300 ppm) and 50% (500 ppm). We conclude that continuous, severe perturbation of GSH in RNM following repeated high PO exposures may lead to inflammatory lesions and cell proliferation, critical steps on the path towards tumorigenicity.     

谷胱甘肽硫转移酶M1与T1基因缺失增加鼻咽癌易感性(英文)

目的在中国西南的广西壮族自治区的鼻咽癌高发区内研究谷胱甘肽硫转移酶 M1与 T1遗传多态性与鼻咽癌易感的相关性。方法病例与对照研究这些酶的遗传多态性(GSTM1和 GSTT1零基因型),鼻咽癌总数为127例,对照207例。结果 GSTM1和 GSqT1零基因型的频数在 NPC 患者中较高,差异达统计学意义(P<0.001)。结论鼻咽癌是广西最常见癌症,GST 酶与多种环境致癌物的解毒相关,同合子缺失 GSTM1和 GSTT1与数种癌相关,生鼻咽癌危险性已知与环境因素如吸烟和 EB病毒感染相关联,我们的结果提示 GSTM1和 GSTF1缺失多态性与增加鼻咽癌易感性相关,若两种解毒酶基因同时缺失对鼻咽癌易感受性意义更重要。     

中国汉族人群hGSTA1基因C-69T多态性分析

目的　研究中国汉族人群中人谷胱甘肽S 转移酶(hGSTA1 )C-69T基因多态性的分布。方法1 4 0例血样本来自中国2 5个省份的汉族人口,用聚合酶链反应 限制性片段长度多态性方法检测hGSTA1 69位点的变异。结果　中国汉族人群GSTA1基因 69位点的野生型纯合子(CC)基因型的分布频率为75 .0 %,突变型纯合子(TT)基因型为0 .7%,杂合子(CT)基因型为2 4 .3 %;C及T两种等位基因的频率分别为87.1 %及1 2 .9%。结论中国汉族人群GSTA1基因呈多态性分布,其等位基因和基因型频率不同于其他种族