丹皮总甙对化学性肝损伤保护作用机制

目的 研究丹皮总苷（ＴＧＭ）对ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ致小鼠化学性肝损伤的保护作用机制。方法 采用ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ所致小鼠化学性肝损伤模型进行研究,用ＴＢＡ法和ＤＴＮＢ法测定ＭＤＡ和ＧＳＨ－Ｐｘ。结果 ＴＧＭ具有促进肝脏糖原合成和提高血清蛋白含量的作用（Ｐ〈０．０１）,可明显降低肝匀浆脂质过氧化产物丙二醛（ＭＤＡ）的含量（Ｐ〈０．０１）及提高血清和肝脏谷胱甘肽过氧化物酶活力（Ｐ〈０．０１）     

肝硬化腹水利尿剂疗效的临床观察研究

利尿剂是治疗肝硬化腹水的主要措施之一,一般推荐单用螺内酯或联合应用呋塞米及其逐渐增量治疗方案.但两种治疗方案疗效及安全性的差异如何,如何量化分析利尿剂治疗肝硬化腹水的疗效,尚缺乏有关临床观察研究.     

不同剂量左氧氟沙星在大鼠胆汁药物浓度分布情况探讨

目的在大鼠模型上,研究不同剂量左氧氟沙星在大鼠胆汁药物浓度分布的情况,并初步探讨左氧氟沙星用于胆道感染的剂量问题。方法选择32只Wistar大鼠分为20,40,50,100 mg.kg-14个剂量组。在给药后30 min,1,2,3,4,5,6,8,10,12 h分别收集血标本和胆汁标本,经HPLC方法检测药物含量,并计算相关药代动力学参数。结果通过比较各组不同时点的血药浓度发现,各时点血药浓度差异均有显著性(P<0.05);而比较各剂量组胆汁药物浓度后发现,20和40 mg.kg-1剂量组各时点均无差异;1～5 h,50和100 mg.kg-1剂量组胆汁药物浓度显著高于其它剂量组;6～8 h,50和40 mg.kg-1剂量组相比差异无显著性,但10～12 h,两剂量组差异具有显著性;10～12 h,50和100 mg.kg-1剂量组相比浓度相差较大,但差异无显著性(P=0.053)。结论由动物模型结果推测,400 mg.d-1剂量用于治疗胆道感染可以满足临床需要,但500 mg.d-1剂量可能更合适临床用药。     

根除幽门螺杆菌对非肿瘤胃黏膜E-钙粘蛋白、死亡相关蛋白激酶基因甲基化的影响

幽门螺杆菌(Hp)感染与胃癌发生密切相关.根除Hp可能降低胃癌发生风险,但其机制未明,且缺乏分子生物学证据[1].Hp感染与胃黏膜中DNA异常甲基化有关,E-钙粘蛋白(E-cad)、死亡相关蛋白激酶(DAPK)基因甲基化是非肿瘤胃黏膜癌变过程中的重要环节[2].本研究采用甲基化特异性聚合酶链反应(MSP)检测Hp根除前后非肿瘤胃黏膜中E-cad和DAPK基因甲基化状态,探讨根除Hp在预防胃癌发生中可能的作用机制.     

溃疡性结肠炎中血浆同型半胱氨酸和褪黑素水平的关联研究

目的 探讨血浆同型半胱氨酸(HCY)和褪黑素(MLT)水平改变与溃疡性结肠炎(UC)的临床关联.方法 收集112例UC患者临床资料,以110名健康体检者为对照.采用高效液相荧光检测法(HPLC-FD)检测血浆HCY、MLT水平,酶联免疫吸附分析(ELISA)法检测血浆叶酸(FA)、维生素B12水平,并分析该四项指标与UC患者临床特征的相关性.结果 UC患者血浆HCY水平高于健康对照[(11.27±7.26)μmol/L比(8.19±4.81)μmol/L,P=0.000],血浆MLT水平低于健康对照[(49.06±31.40)pg/ml比(64.28±41.16)pg/ml,P=0.008],血浆FA水平低于健康对照[(7.64±1.95)nmol/L比(9.14±1.23)nmol/L,P=0.005]、血浆维生素B12水平低于健康对照[(108.64±32.22)pmol/L比(112.64±33.33)pmol/L,P=0.004].UC患者血浆HCY、MLT水平与UC病情分度、病变范围、病程、红细胞沉降率(ESR)、C反应蛋白(CRP)水平无关.UC患者血浆HCY与MLT水平间无明显相关性.结论 UC患者血浆HCY水平高于健康对照,MLT水平低于健康对照,但二者间无明显相关性.

Abstract：

Objective To explore the clinical correlation of the variation of plasma homocysteine (HCY), melatonin (MLT) and ulceative colitis (UC). Methods The clinical data of 112 UC patients was collected, and 110 normal healthy persons as control. The level of plasma HCY and MLT was detected by high pressure liquid chromatography-fluorescence detection (HPLC-FD) method. The level of plasma folate ( FA) and vitamin B12 was detected by enzyme-linked immunosorbent assay (ELISA) method. The correlation of these four indexes and UC was analyzed. Results The serum level of HCY in UC patients was significantly higher than that in normal healthy persons [(11. 27± 7.26) μmol/L vs (8. 19±4. 81) μmol/L, P = 0. 000]. The serum level of MLT in UC patients was significantly lower than that in normal healthy persons [(49. 06 + 31. 40) pg/ml vs (64. 28±41. 16) pg/ml,P=0. 008]. The serum level of FA in UC patients was significantly lower than that in normal healthy persons [(7. 64 + 1.95) nmol/L vs (9. 14 + 1.23) nmol/L, P = 0. 005]. The serum level of vitamin B12 in UC patients was significantly lower than that in normal healthy persons [(108. 64 ±32. 22) pmol/L vs (112. 64±33. 33) pmol/L, P = 0. 004]. There was no correlation between plasma HCY, MLT and UC disease activity degree, range, disease duration, erythrocyte sedimentation rate (ESR), or C reactive protein (CRP) in UC patients. There was no significant correlation between MLT and HCY in UC patients. Conclusions The serum level of HCY is higher in UC patients than that in normal control, and MLT is lower than that in normal control. However there is no significant correlation between them.     

小鼠结肠癌中巨噬细胞金属弹力蛋白酶对血管抑素生成和肿瘤血管生长的影响

目的 在小鼠模型体内探讨巨噬细胞金属弹力蛋白酶(macrophage metalloelastase,MME)分解纤溶酶原生成有生物学功能的血管抑素的途径,及其对肿瘤生长和微血管密度(MVD)的抑制作用.方法 构建重组质粒pEGFP-C1-MME.给90只小鼠分别皮下接种稳定转染pEGFP-C1-MME(MME转染组)、空质粒pEGFP-C1(空质粒转染组)和未转染(未转染组)的CT-26细胞,每组30只.应用放射性碘标纤溶酶原及其示踪技术分析体内血管抑素的生成情况.结果 各组肿瘤标本进行SDS-PAGE电泳,在MME转染组电泳胶中,蛋白相对分子质量为35×103和38×103的区域放射性明显高于空质粒转染组和未转染组(P值均为0.00).Western印迹检测发现三组均检测出35×103和38×103片段表达,通过灰度扫描分析发现上述2个片断在MME转染组表达强度为9.32±1.52和5.61±2.24,明显高于空质粒组(2.47±0.23和0.67±0.12,P值均为0.00)和未转染组(1.21±0.69和0.86±0.44,P值均为0.00).MME转染组MVD平均值和血管内皮生长因子(VEGF)荧光表达强度均明显低于空质粒转染组和未转染组(P值均为0.00).MME转染组小鼠皮下种植瘤平均体积小于空质粒组和未转染组(P值均为0.00).结论 MME是与血管抑素生成密切相关的间质金属蛋白酶,同时具有抑制结肠肿瘤血管形成的作用.

Abstract：

Objective To determine the pathway of macrophage metalloelastase (MME)generate active angiostatin by decomposing plasminogen and its effect on inhibiting growth of tumor and microvessel density (MVD) in vivo in mouse models. Methods The recombined plasmid pEGFPC1-MME was constructed. Thirty mice were subcutaneously inoculated with CT-26 cells that were stably transfected with pEGFP-C1-MME (MME-transfected group), 30 with CT-26 cells transfected with empty vector pEGFP-C1 (vector-transfected group) and 30 with CT-26 cells (non-transfected group). Radioiodination and radioisotope tracer were used to explore the pathway of angiostatin generation in vivo. Results SDS-PAGE electrophoresis analysis revealed that, in the PAGE gel contained the protein with molecular weights of 35 000 and 38 000, radioactivity in MME-transfected group was significantly higher than vector-transfected and non-transfected groups (P = 0. 00).Western blotting analysis demonstrated two bands containing 35 000 and 38 000 fragments in three groups. Quantification of the protein signals by image analysis revealed that the levels of 35 000 and 38 000 fragments were obviously increased in MME-transfected group (9.32±1.52 and 5.61±2.24,respectively) than those in vector-transfected (2.47 ± 0.23 and 0. 67 ± 0. 12, respectively) and nontransfected (1.21±0. 69 and 0. 86 ± 0.44, respectively) groups (P= 0.00). The average value of MVD and fluorescent express of vascular endothelial growth factor (VEGF) were lower in MMEtransfected group when compared with those in vector-transfected and non-transfected groups (P =0.00). The average tumor size in MME-transfected group was small in comparison with vectortransfected and non-transfected groups (P= 0.00). Conclusions MME is demonstrated to be one of matrix metalloproteinase that closely related with angiostatin production and has inhibitory effect on tumor growth in tumor-bearing mice.     

褪黑素对大鼠肝纤维化的影响及部分机制研究

目的探讨褪黑素(melatonin,MEL)对大鼠肝纤维化的影响及部分机制。方法 111只雄性SD大鼠随机分为6组:正常对照组、模型对照组、N-乙酰-L-半胱氨酸组(N-ac-etyl-L-cysteine,NAC)组、褪黑素低、中、高剂量组(剂量分别为2.5、5、10 mg.kg-1)。采用四氯化碳(carbon tetrachloride,CCl4)制备大鼠肝纤维化模型,同时腹腔注射褪黑素,HE染色和VG胶原纤维染色观察肝脏病理改变;生化法测定肝脏丙二醛(malondialdehyde,MDA)含量和谷胱甘肽过氧化物酶(glutathione peroxidase,GPx)、超氧化物歧化酶(superox-ide dismutase,SOD)活性;RT-PCR法测定肝组织中α1(I)前胶原(α1(I)procollagen)mRNA表达;原位灌注加密度梯度离心法分离正常SD大鼠肝脏星状细胞,在培养的肝星状细胞中加入脂多糖(lipopolysaccharide,LPS)进行刺激,用MTT法测定不同浓度的MEL对肝星状细胞增殖的抑制作用。结果和模型组比较,MEL(10 mg.kg-1)组肝纤维化评分较低(P<0.05),MEL能明显降低肝匀浆MDA含量,升高SOD、GPx活性,MEL(10 mg.kg-1)组、NAC组大鼠肝组织α1(I)型前胶原mRNA表达明显减少(P<0.05);培养的肝星状细胞经LPS刺激后A值增大,与LPS组相比,LPS+NAC组和LPS+MEL(0.1 mmol·L-1)组A值明显减小(P<0.05)。结论 MEL对大鼠肝纤维化具有改善作用,其机理可能与抗氧化、抑制前胶原基因转录和抑制肝星状细胞增殖有关。     

瑞巴派特对NSAIDs肠病中肝线粒体功能的影响

目的 探讨瑞巴派特对小鼠非甾体类抗炎药(NSAIDs)肠病模型中肝线粒体功能的影响研究.方法 选用双氯芬酸钠2.5 mg/kg灌胃3 d制备小鼠NSAIDs肠病模型,实验分为正常对照组、模型对照组、瑞巴派特组(400 mg/kg)、谷氨酰胺组(1 000 mg/kg),各组给药时间3 d,正常对照组和模型对照组以溶媒灌...     

超声内镜对上消化道黏膜隆起性病变的诊断价值

目的 探讨超声内镜(EUS)对上消化道隆起性病变诊断和鉴别诊断的价值.方法 分析176例上消化道隆起性病变EUS检查结果.结果 176例上消化道隆起性病变中,按病变部位分为食管49例(28%),贲门6例(3%),胃96例(55%),十二指肠25例(14%).按病变类型分为间质瘤67例,外压35例,黏膜下囊肿25例,息肉...