Objective To investigate the relationship between the expressions of P-gp, GST-π and C-erbB-2 and clinicopathologic characteristics as well as prognosis in breast cancer. Methods The expressions of P-gp， GST-π and C-erbB-2 were detected by immunohistochemistry in 48 cases of breast cancer, and histopathologic characteristics as well as 5-year survival rate of these cases were analyzed. Results There was no significant difference in the expressions of P-gp and GST-π with age, histologic grade, number of lymph node metastasis and TNM stage of breast cancer ( P ＞ 0.05). There was significant difference in expression of C-erbB-2 with histologic grade, number of lymph node metastasis and TNM stage of breast cancer （ P ＜ 0.05）. Positive rate of P-gp expression in breast cancer with positive C-erbB-2 expression was remarkably higher than that in breast cancer with negative C-erbB-2 expression ( P ＜ 0.05) . Positive rate of GST-π and C-erbB-2 expression in survivals within 5 years was remarkably lower than that in deaths within 5 years ( P ＜ 0.01). Conclusion P-gp participates primary drug-resistance mechanism of breast cancer. The possibility of primary drug-resistance is higher in breast cancer with positive C-erbB-2 expression. The expression of C-erbB-2 helps to evaluate prognosis and the result of treatment in breast cancer.
ObjectiveTo investigate the clinical values of serum histidine decarboxylase (HDC), D-lactate, and alpha-glutathione S-transferase (α-GST) for diagnosing intestinal mucosal injury of patients with intestinal obstruction. MethodsThe expression levels of serum HDC, D-lactate, and α-GST in 28 patients with strangulated intestinal obstruction, 19 patients with simple intestinal obstruction, 17 patients with acute simple appendicitis, and 20 healthy volunteers were determined by enzyme linked immunosorbent assay (ELISA) before the treatment, and then the area under receiver operating characteristic curve (AUC) of these diagnostic indices were compared. In addition, the occurrence rates of systemic inflammatory response syndrome (SIRS) and infectious complications (abdominal cavity infection and pulmonary infection) were closely observed. The relevances of SIRS and infectious complications and the expression levels of these three diagnostic indices were analyzed. ResultsThe expression levels of serum HDC, D-lactate, and α-GST of the patients with strangulated intestinal obstruction were the highest among all the patients (Plt;0.01), and the expression levels of these three indices in the patients with simple intestinal obstruction were higher than those of the patients with acute simple appendicitis (Plt;0.05). The AUC of HDC (0.913) was larger than that of D-lactate (0.872) and α-GST (0.836) (P=0.000, P=0.000, respectively). When the cut off value of HDC was 31.00 μg/L, the sensitivity, specificity, false negative rate, and false positive rate of HDC were 74.5%, 94.6%, 25.5%, and 5.4%, respectively, which were all better than those of D-lactate and αGST. The occurrence rates of SIRS and abdominal cavity infection of the patients with strangulated intestinal obstruction were significantly higher than those of patients with simple intestinal obstruction (P=0.046) and acute simple appendicitis (P=0.027); while there was not significantly different of pulmonary infection among all the patients (P=0.728). The expression level of serum HDC in patients with strangulated intestinal obstruction suffered from SIRS (P=0.000) or abdominal cavity infection (P=0.002) was significantly higher than that of not-suffered from SIRS or uninfected patients. Meanwhile, the expression levels of serum D-lactate and α-GST in the patients with strangulated intestinal obstruction suffered from SIRS were higher than those of notsuffered from SIRS patients (P=0.032, P=0.021, respectively). The expression levels of HDC, D-lactate, and α-GST were significantly correlated with SIRS and abdominal cavity infection (Plt;0.05), among which the level of HDC and the incidence of SIRS had the highest correlation (r=0.608, P=0.001). ConclusionHDC may be a more effective index for diagnosing intestinal mucosal injury of patients with intestinal obstruction.
ObjectiveTo evaluate the effect of ZnPP Ⅸ on the expressions of heme oxygenase-1 (HO-1) and glutathione-Stransferase-π （GST-π） and the chemosensitivity of drug-resistant hepatic carcinoma cell line Bel/Fu, and explore it’s possibility to reverse drug-resistance and the relevant regulating mechanism. Methods①MTT assay was adopted to detect the drug sensitivity for adriamycin, mitomycin, and 5-fluorouracil of Bel/Fu cell after ZnPP Ⅸ being induced for 24 h. ②RTPCR was carried out to detect the expressions of HO-1 and GST-π mRNA after Bel/FU cells being treated with different concentrations ZnPP Ⅸ for 24 h. ResultsAfter Bel/Fu cells being treated with ZnPP Ⅸ for 24 h, the 50% inhibiting concentration (IC50) for drugs was decreased dramatically （Plt;0.05）. Meanwhile, the expressions of HO-1 and GST-π mRNA in the treated cells also decreased dose-dependently (Plt;0.01). ConclusionsZnPP Ⅸ can increase the chemosensitivity of Bel/FU cells by down-regulation of HO-1 and GST-π expression. ZnPP Ⅸ is a potential agent to reverse multidrug resistance of hepatic carcinoma cells.
ObjectiveTo systematically review the association between glutathione S-transferase pi (GSTP1) Ile105Val (A/G) and the risk of cutaneous melanoma. MethodWe searched PubMed, EMbase, CNKI and WanFang Data to identify case-control studies which investigated the association between GSPT1 Ile105Val (A/G) polymorphism and the risk of cutaneous melanoma from their inception to June 31th 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed by using RevMan 5.3 software. ResultsA total of 4 case-control studies involving 978 cutaneous melanoma cases and 796 controls were included. The results showed that: the GSPT1 Ile105Val (A/G) polymorphism was significantly associated with the risk of cutaneous melanoma in the dominant model (GG+GA vs. AA: OR=1.22, 95%CI 1.01 to 1.48, P=0.04), but no significant association was found in the recessive model, heterozygote model, and homozygote model (GG vs. CA+AA: OR=1.18, 95%CI 0.86 to 1.60, P=0.30; GA vs. AA: OR=1.20, 95%CI 0.98 to 1.47, P=0.08; GG vs. AA: OR=1.28, 95%CI 0.92 to 1.77, P=0.14). ConclusionCurrent evidence shows, The GSTP1 Ile105Val (A/G) polymorphism is associated with the risk of cutaneous melanoma. Due to limited quantity and quality of the included studies, more high-quality large-scale studies are needed to verify the above conclusion.
【摘要翻譯】 一 氧化氮合酶( NOS) -2( NOS-2) 的誘導和一氧化氮產物增加是過敏性氣道疾病的共同特征。嚴重哮喘與氣道S-亞硝基硫醇減少相關。S-亞硝基硫醇是NO的生化產物, 可通過促炎癥轉錄因子NF-κB 的S-亞硝基化抑制炎癥反應。因此, 重建氣道S-亞硝基硫醇對治療可能有益。我們對此假設在以卵清蛋白誘導的過敏性炎癥大鼠模型中進行驗證。未使用或使用卵清蛋白致敏的動物均在卵清蛋白激發前于氣管內灌注S-亞硝基谷胱甘肽( GSNO;50 μl, 10 mM) , 并在48 h 以后進行分析。GSNO 給藥增加了肺組織S-亞硝基硫醇水平。與對照組比, GSNO 降低了卵清蛋白致敏動物NF-κB 的活性, 但對支氣管肺泡灌洗細胞總數、分類計數及杯狀細胞化生標記物均無顯著影響。GSNO給藥也改變了HIF-1 的活性, 導致未致敏大鼠HIF-1 活化,但抑制卵清蛋白致敏大鼠的HIF-1 活性。我們使用NOS-2基因敲除小鼠來評價內源性一氧化氮合成酶-2 在調節NF-κB和( 或) HIF-1 活性及氣道過敏性炎癥的作用。盡管在NOS-2 基因敲除小鼠中卵清蛋白誘導的NF-κB 活力輕度增高, 這與支氣管肺泡灌洗中性粒細胞輕度增加有關, 其他的過敏性炎癥指標和HIF-1 活性在NOS-2 基因敲除及野生型小鼠之間卻無明顯相差。總體來說, 我們的研究表明GSNO灌注能抑制氣道過敏性炎癥中NF-κB 活性, 但是并不能顯著地影響大部分炎癥及杯狀細胞化生指標, 這樣可能因為對其他信號通道( 比如HIF-1) 的影響而限制了它的治療價值。【述評】 GSNO 是近年哮喘治療研究的熱點。既往的研究發現GSNO 在哮喘治療中有一定前景。本研究卻發現GSNO 氣管內滴注雖能抑制過敏性氣道炎癥中NF-κB 活性,但并不能顯著抑制氣道炎癥反應及杯狀細胞化生這兩個哮喘關鍵病理改變, 可能與GSNO 同時影響了HIF-1 等其他信號通路有關。該研究表明GSNO 對哮喘氣道炎癥治療效果有限, 同時表明哮喘氣道炎癥調控機制較為復雜, 治療藥物的設計需考慮多種信號通路對哮喘氣道炎癥的影響。
ObjectiveTo establish a cell inflammation model induced by tumor necrosis factor-α (TNF-α) in human bronchus epithelial cells, and investigate the effects of glutathione S-transferase mu 5 (GSTM5) on the inflammation and oxidative stress. Methods16HBE cells were treated with TNF-α (10 ng/mL, 24 h) in the absence or presence of the constructed GSTM5 eukaryotic expression vector (1 μg/mL). The concentration of malondialdehyde (MDA) and total antioxidation capacity (T-AOC) were detected by colorimetric method. The survival rate of cells was assessed by the methyl thiazolyl tetrazolium (MTT) assay. The transcription level of NADPH oxidase-1 (NOX1), NOX2, NOX3, NOX4, NOX5, dual oxidase-1 (DUOX1) and DUOX2 were evaluated by RT-PCR. Western blot was performed to investigate the protein levels of NOX1 and NOX2. ResultsTNF-α simulation significantly increased the level of MDA in cells, and decreased the level of T-AOC and survival rate of 16HBE. When transfected with the GSTM5 eukaryotic expression vector, the concentration of MDA significantly decreased (P < 0.05), and the activation of T-AOC increased dramatically (P < 0.05). Consequently, the survival rate of 16HBE in the GSTM5 group improved (P < 0.05). The 16HBE cells transfected with the constructed GSTM5 eukaryotic expression vector had a lower transcription and protein levels of NOX1 and NOX2 (all P < 0.01). There were no significant changes in the mRNA expressions of NOX3, NOX4, NOX5, DUOX1 or DUOX2. ConclusionGSTM5 may down-regulate the transcription level of NOX1 and NOX2 to reduce the inflammation and oxidative stress induced by TNF-α.
Objective To explore changes of 3’-glutamylcysteine synthetase( γ-GCS)and reduced glutathione(GSH)in patients with bronchial asthma．Methods Ten patients with acute asthma were enrolled and treated for six weeks according to guideline recommendations．Levels of -GCS，GSH and malondialdehyde(MDA)in total cells in induced sputum and GSH，MDA，reactive oxygen(ROS)in selum were measured and compared before and after therapy．Ten healthy volunteers were as normal contro1．Meanwhile，the pulmonary function(FEVl％pred)was measured and asthmatic symptoms were quantified using Hogg’s way．Results A．In serum and sputum of the asthma patients，GSH were lower and MDA were higher before treatment than those of the control(Plt;0．01)．And -GCS in induced sputumwere higher before treatment than those of contro1．B．After treated for six weeks．levels of GSH in serum and sputum of the asthma patients increased copmpared to baseline(all Plt;0．01)，but were still lower than that of control(Plt;0．05)．Activities of MDA in serum and sputum and -GCS in sputum were elevated compared to baseline(Plt;0．01)，but still higher than that of control(all Plt;0．05)．C．Levels of GSH in serum of all patients were correlated negatively witll asthmatic symptom scores and levels of MDA and ROS(r=－0.701，－0.901，－0.878；Plt;0.05，lt;0.01，lt;0.01)．There was a positive relationship between levels ofGSH in serum and FEV1％pred(r=0．854，Plt;0．01)．In induced sputum，activities of 3’-GCS in all patients was correlated positively with their asthmatic symptom scores and level of MDA f r=0．804，0.926；Plt;0.05，lt;0.叭)．Conclusion γ-GCS and GSH may participate the reaction of
目的 探討異氟醚通過抑制細胞間黏附分子（ICAM-1）表達參與減輕肝臟缺血-再灌注（IR）損傷的可能調節機制。 方法 32只雌性SD大鼠分為4組。A組大鼠行腹腔注射1%戊巴比妥鈉40 mg/kg麻醉，進行手術但不阻斷入肝血流；B組1%戊巴比妥鈉麻醉后行部分肝臟IR；C組大鼠僅接受1.0 MAC異氟醚吸入麻醉，不阻斷血流；D組采用1.0 MAC異氟醚麻醉，建立肝臟IR模型。肝臟缺血60 min，再灌注3 h后取肝組織和血液標本，檢測血清丙氨酸轉氨酶（ALT）和天冬門氨酸轉氨酶（AST）、肝組織ICAM-1和肝組織還原型谷胱甘肽（GSH）、脂質過氧化物丙二醛（MDA）和超氧化物歧化酶（SOD）含量。 結果 與戊巴比妥鈉麻醉比較，采用異氟醚處理后明顯降低血清ALT和AST的水平，再灌注肝組織內GSH、SOD含量明顯高于而MDA含量降低，同時抑制肝組織ICAM-1的表達。 結論 異氟醚麻醉能夠有效減輕肝臟IR損傷，抑制氧自由基的生成和釋放，具體機制可能與抑制ICAM-1表達致使細胞內GSH含量增加密切相關。
Objective To investigate the effects of glutathione (GSH) on survival of the random skin flap in rats and the probable mechanism that contribute to this effect. Methods Twenty SD rats with 200-250 g in weight, were randomly divided into the experimental group and control group(n=10). Random flap of 8 cm×2 cm in size was made on the back of each rat with the pedicel on the angular of the scapular. GSH(250 mg/kg) and NS of the same dose were injected into the abdominal cavity of rats in the experimental groupand the control group immediately after the operative, 1st and 2nd days respectively. The rats were killed on the 7th day after the operation. The tissue pathology, the survival rate of the flap, the superoxide dismutase(SOD) activity and malonyldialdehyde (MDA) level were compared between two groups. Results The mean survival rate of the flap on the 7th day in the experimental group（56.77%±10.67%） was higher than that in the control group(40.16%±7.12%)(Plt;0.05).SOD activity in experimental group （306.06±84.87 U/mgprot）was higher than that in the control group （224.79±27.12 U/mgprot）, while MDA level （3.835±0.457 nmol/mgprot）was lower than that in the control group (6.127±0.837 nmol/mgprot)(Plt;0.05). Histological observation showed that the neutrophil infiltration was less in experimental group than that in the control group; that the experimental group was surperior to the control group in angiogenesis, fibroblasts, fair cells and cuaneous gland. Conclusion The intraperitoneal use of GSH may promote the survival rate of the random flaps and the possible mechanism for improvement may lies in that the GSH can reduce the level of oxygen free radical and lipidperoxidation,and lessen neutrophil infiltration.
Objective To investigate the effects of glutathione S-transferase M5 (GSTM5) on the inflammation in human bronchial epithelial 16HBE cells and its possible molecular mechanisms. Methods Acute lung injury cell model was constructed with 16HBE cells induced by tumour necrosis factorα (TNF-α, 10 ng/mL). The cells were devided into a control group, a TNF-α group (TNF-α), a GSTM5 group (GSTM5+TNF-α), a negative control group (negative control plasmid+TNF-α). GSTM5-GFP plasmid and negative control plasmid were respectively transfected to the cells of the GSTM5 group and the negative control group using Lipofectamine2000. The contents of interleukin-6(IL-6), IL-8, IL-10 in the cell supernatant were measured by ELISA.The expression of nuclear factor-κB (NF-κB) mRNA was detected by RT-PCR, and the expression of NF-κB, phospho-NF-κB, p38, phospho-p38 protein were detected by Western blot. Results The GSTM5-GFP eukaryotic expression vector was successfully constructed and transfected successfully confirmed by fluorescence microscope. The contents of IL-6, IL-8, IL-10 in the TNF-α-induced cell supernatant were significantly higher than those in the control group(P < 0.05), and the contents of IL-6, IL-8, IL-10 in the GSTM5 group were lower than those in the TNF-α group (P < 0.05)with statistically significant difference. At the same time, the total NF-κB mRNA, phospho -NF-κB and phospho-p38 protein were increased in TNF-α stimulated cells compared with the control group (P < 0.05), while the GSTM5 group was lower than that in the TNF-α group and the negative control group (P < 0.05). Conclusion Overexpression of GSTM5 inhibits the phosphorylation of p38MAPK and NF-κB and down-regulates the inflammation of TNF-α-induced human bronchial epithelial 16HBE cells.