P糖蛋白和谷胱甘肽—S—转移酶在肾细胞癌中的表达

探讨肾细胞癌与多药耐药的关系，方法：应用免疫组化方法，检测４例术前未进行化疗的肾细胞癌和１６例正常肾组织中的Ｐ糖蛋白和谷胱甘肽－２转移－π表达。结果：Ｐ－ａｇ和ＧＳＴ－π外地１６例正常肾组织中的表达率均匀１００％，在４４例肾细胞癌组织中分别为６３．６５和５４．５％Ｐｇ，Ｐ－ｇｐ和／或ＧＳＴ－π阳性表达率为７９．５％。     

猪带绦虫囊尾蚴囊液谷胱甘肽S转换酶活性测定

目的：探讨猪带绦虫囊尾蚴囊液内谷胱甘肽Ｓ转换酶（ＧＳＴ）的活性。方法：测定酶催化反应后底物浓度的变化,计算ＧＳＴ活力单位。结果：囊液经１：２０稀释,重复４次测定酶促管与非酶促管吸光值,测得平均ＧＳＴ活性为６１．８４活力单位;囊液冻干品则几无ＧＳＴ活性。结论：囊液中存在游离形式的ＧＳＴ活性,对筛选保护性抗原和可能的化疗靶分子具有潜在意义。     

胃癌及癌旁黏膜组织胎盘型谷胱甘肽S-转移酶的表达

①目的 探讨胎盘型谷胱甘肽Ｓ－转移酶（ＧＳＴπ）在胃癌中表达的意义。②方法 应用ＬＳＡＢ免疫组化方法检测了胃癌及癌帝黏膜组织ＣＳＴπ的表达。③结果 正常胃黏膜组织ＧＳＴπ阳性表达率为１６．７％,肠上皮化生和不典型增生腺体ＧＳＴπ阳性表达率分别为７１．４％和１００．０％,显著高于正常胃黏膜（Ｘ＾２＝８．４,１９．４,Ｐ〈０．０１）。胃癌组织中ＧＳＴπ阳性表达率为８０．３％,高分化腺癌和低分化腺癌ＧＳ     

Effects of valproate on xenobiotic biotransformation in rat liver

Male Wistar rats werein vivo exposed for 2 weeks to 100 g/ml sodium valproate by subcutaneous implantation of osmotic pumps and hepatocytes were isolated. As anin vitro model co-cultures of rat hepatocytes with epithelial cells were daily treated with valproate (25, 50, 100, 200g/ml) for 2 weeks. In both models the cytochrome P-450 content and the enzymatic activities of 7-ethoxycoumarinO-deethylase, aldrin epoxidase and glutathioneS-transferase were determined in valproate-treated hepatocytes, in controls and in phenobarbital-induced cells. It appeared that in both systems the cytochrome P-450 content and the 7-ethoxycoumarinO-deethylase activity increased significantly after valproate treatment. On the other hand, the activities of aldrin epoxidase and glutathioneS-transferase decreased. A cDNA probe, encoding rat P450IIB2 was used to determine whether mRNAs encoding the P450IIB subfamily were induced by valproate. It became clear that the inducing effect of valproate was even more pronouncedin vitro thanin vivo.     

亚硝基谷胱甘肽对大鼠肝微粒体谷胱甘肽转移酶的激活及机制

目的　探索一氧化氮供体亚硝基谷胱甘肽(GSNO)能否在体外通过S 亚硝酰化机制激活大鼠肝微粒体谷胱甘肽转移酶 (mGST)。方法　微粒体粗提物与GSNO体外共孵育 ,测定mGST催化动力学改变 ,结合N 乙基马来酰亚胺 (NEM )再激活实验和二巯基苏醇 (DTT)逆转实验 ,以及酶蛋白游离巯基和酶S 亚硝酰化蛋白的改变 ,研究酶的激活机制。结果　GSNO在 0 .12 5～ 2mmol·L- 1浓度范围内呈浓度和时间 (3～ 15min)依赖性地激活mGST ,NEM对酶的再激活效应消失 ,DTT可以逆转上述激活作用 ,同时酶蛋白游离巯基浓度依赖性减少 ,而S 亚硝酰化蛋白浓度依赖性增多。结论　GSNO体外可激活大鼠肝mGST ,激活机制可能与mGST第 4 9位半胱氨酸 (Cys4 9)的巯基被亚硝酰化形成S 亚硝基硫醇结构有关。     

三种耐药蛋白在胃癌中的表达及意义

目的：探讨多药耐药蛋白(MRP)、谷胱甘肽转移酶Pi(GST—π)和肺耐药蛋白(LRP)在胃癌中的表达及意义。方法：应用免疫组化S—P法，检测MRP、GST—π和LRP在90例胃癌及30例正常胃黏膜中的表达。结果：MRP、GST—π及LRP在胃癌中的阳性表达率分别为92．2％、99．0％和93．3％，均显著高于其在正常胃黏膜中的表达(P＜0．05)，且MRP、GST—π和LRP在高、中分化腺癌中的表达显著高于在低分化腺癌和黏液癌中的表达(P＜0．05)。但它们的表达与胃癌浸润深度、淋巴结转移无关。结论：MRP、GST—π和LRP在胃癌中高表达，在胃癌的原发性耐药中起重要作用。这可能是胃癌化疗效果差、死亡率高的重要原因之一。     

A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States)

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1)genetic polymorphisms are involved in the activation and detoxification ofchemical carcinogens found in tobacco smoke; thus they may influence hostsusceptibility to lung cancer. In this study at Massachusetts GeneralHospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) weevaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms andlung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspIheterozygous genotype was present in 18 percent of cases and 16 percent ofcontrols, and one percent of cases and controls were CYP1A1 MspI homozygousvariant. The GSTM1 null genotype was detected in 54 percent of cases and 52percent of controls. After adjusting for age, gender, pack-years of smoking,and years since quitting smoking, while neither the CYP1A1 MspI heterozygousgenotype alone nor the GSTM1 null genotype alone were associated with asignificant increas e in lung cancer risk, having both genetic traits wasassociated with a twofold increase in risk (95 percent confidence interval[CI] = 1.0-3.4). Our data did not provide enough evidence for a substantialmodification of the effect of pack-years on lung cancer risk by the CYP1A1MspI and GSTM1 genotypes. However, limitations of our study preclude aconclusion about this potential interaction.     

Nuclear factor erythroid‐derived 2–related factor 2 activates glutathione S‐transferase expression in the midgut of Spodoptera litura (Lepidoptera: Noctuidae) in response to phytochemicals and insecticides

Detoxication enzymes play an important role in insect resistance to xenobiotics such as insecticides and phytochemicals. We studied the pathway for activating the expression of glutathione S‐transferases (GSTs) in response to selected xenobiotics. An assay of the promoter activity of GST epsilon 1 (Slgste1) of Spodoptera litura led to the discovery of a cis‐regulating element. An antioxidant response element was activated in response to indole‐3‐carbinol (I3C) and chlorpyrifos (CPF) and was able to bind with the xenobiotic sensor protein nuclear factor erythroid‐derived 2–related factor 2 (SlNrf2). SlNrf2 and Slgste1 were responsive to reactive oxygen species induced by I3C and CPF in a S. litura cell line, as well as in S. litura midguts. SlNrf2 RNA interference (RNAi) reduced the message RNA levels of Slgste1 and the peroxidase activity of GSTs in response to I3C, xanthotoxin, CPF and deltamethrin. SlNrf2 RNAi and inhibitor treatment of GST activity decreased the viability of I3C‐treated cells. These results indicate that SlNrf2 activates the expression of GSTs in response to oxidative stresses caused by exposure to xenobiotics.     

白芍粗提物及芍药苷对变异链球菌作用的体外实验

目的 研究白芍粗提物及其主要成分芍药苷对变异链球菌的作用。 方法 采用醇提法制取白芍粗提物,通过高效液相色谱法测定白芍粗提物的主要活性成分,分别观察白芍粗提物及其主要成分芍药苷在不同药物浓度下对变异链球菌的粘附、产酸、合成水不溶性胞外多糖以及葡聚糖转移酶(GTF)比活力等方面的影响。 结果 白芍粗提物及芍药苷对变异链球菌的体外生长最小抑菌浓度(MIC)分别为3.130和1.770 mg/mL,当两者的浓度分别为≥1.565和≥0.885 mg/mL时,有明显的抑制变异链球菌粘附、合成水不溶性胞外多糖和GTF比活力的作用(P<0.05); 当白芍粗提物浓度为3.130 mg/mL时,有明显的抑制变异链球菌产酸的作用(P<0.05),而不同浓度的芍药苷对变异链球菌产酸均无影响(P>0.05)。不同浓度白芍粗提物组和芍药苷组的水不溶性胞外多糖含量和GTF比活力之间均呈正向直线相关。 结论 白芍粗提物可抑制变异链球菌的粘附、产酸、合成水不溶性胞外多糖和GTF活性,其主要活性成分芍药苷可抑制变异链球菌的粘附、合成水不溶性胞外多糖和GTF活性,但不影响变异链球菌的产酸活动。