Expression of gelatinases within the trabecular bone compartment of ovariectomized and parathyroidectomized adult female rats

Ovariectomized (ovx) and parathyroidectomized (ptx) rat models of disturbed bone metabolism have been widely used in evaluating bone changes resulting from hormonal depletion, and are characterized by elevated and depressed bone turnover, respectively. We report here the expression of gelatinases extracted from native trabecular bone in these models. Nine-month-old female Sprague-Dawley rats were sacrificed after 3 weeks following ovx or 10 days post ptx to determine the influence of these procedures on the levels of proximal tibial bone tissue gelatinases. Identification and quantitation of these enzymes were performed via gelatin gel zymography of native tissue extracts and laser densitometry of developed gels, respectively. In the ptx model, a reduction in tissue levels of pro- and active-MMP-2 and 45 kDa activated fragment was seen, whereas ovx exhibited significant increases in these enzymes. The MMPs are therefore clearly under the influence of factors known to modulate bone remodeling in vivo. The study of MMP levels directly extracted from bone using these experimental models may assist in developing management regimes for metabolic bone diseases through the use of drugs aimed at controlling turnover.     

脊髓损伤后热休克蛋白27、表皮脂肪酸结合蛋白和金属蛋白酶组织抑制因子-1的基因表达及甲基强的松龙对其表达的影响

目的研究脊髓损伤后热休克蛋白27(HSP27)、表皮脂肪酸结合蛋白(FABPs)和金属蛋白酶组织抑制因子-1(TIMP-1)的基因表达及甲基强的松龙(MP)对其表达的影响.方法SD大鼠30只.随机分为假手术组、单纯脊髓损伤组(损伤组)及脊髓损伤+大剂量MP治疗组(MP组),每组10只.应用改良的Allen's打击法致T8脊髓损伤.MP组大鼠伤后即刻从尾静脉内注射大剂量MP(30mg/kg).损伤后24h切取损伤平面上下0.5cm的脊髓组织,进行RT-PCR反应,检测HSP27、FABPs和TIMP-1的基因表达.结果术后24h假手术组HSP27、FABPs和TIMP-1的基因表达相对丰度分别为0.0643±0.0152、0.6413±0.1005和0.7091±0.0577;损伤组上述三个因子的表达升高,分别为1.0013±0.3861、1.2187±0.2851和0.8971±0.1092,与假手术组比较差异有显著性(P＜0.01、P＜0.05、P＜0.05);MP组上述三个因子的表达继续升高,分别为1.2858±0.1384、1.7122±0.1766和1.2081±0.1093,与损伤组比较差异有显著性(P＜0.05、P＜0.01和P＜0.01).结论脊髓损伤后,邻近损伤处的脊髓组织中HSP27、FABPs及TIMP-1的基因表达显著增高,大剂量MP能进一步促进三个因子表达,发挥组织保护作用.     

无排卵性功能失调性子宫出血患者子宫内膜雌、孕激素受体及基质金属蛋白酶表达变化的研究

目的研究无排卵性功能失调性子宫出血(功血)患者子宫内膜雌激素受体(ER)、孕激素受体(PR)、IV型胶原、基质金属蛋白酶-9(MMP-9)及其抑制物-1(TIMP-1)的表达,探讨无排卵性功血的发病机制。方法采用免疫组化法检测20例正常增殖期子宫内膜(对照组)和66例无排卵性功血患者(病例组)子宫内膜腺上皮和基质细胞ER、PR、IV型胶原、MMP-9及TIMP-1表达。结果病例组子宫内膜腺上皮和基质ER、PR表达高于对照组(P<0.05),MMP-9水平明显增加(P<0.05),MMP-9/TIMP-1比值升高(P<0.01),IV型胶原含量明显下降(P<0.01)。相关分析显示,无排卵性功血患者子宫内膜MMP-9水平与ER、PR均呈正相关(r=0.605,P<0.05;r=0.697,P<0.05)。结论无排卵性功血患者子宫内膜出血原因可能与雌激素作用下ER、PR表达失调有关,且MMP-9水平异常升高,导致细胞外基质过度降解,临床表现为子宫不规则出血。     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.     

尿激酶溶栓对大鼠局灶性脑缺血基质金属蛋白酶-9表达的影响

目的研究大鼠局灶性脑缺血后应用尿激酶(urokinase,UK)溶栓对基质金属蛋白酶-9(Matrix metalloproteinase-9,MMP-9)表达的影响,探讨MMP-9在UK溶栓引起的再灌注损伤及出血性转化中的作用。方法将实验动物随机分成3组进行研究(1)UK溶栓组;(2)缺血对照组;(3)假手术组。分别用免疫组织化学方法分析3组缺血后24hMMP-9的表达,对比研究两组MMP-9表达的差异性。结果缺血后24h前两组均有MMP-9的表达,但是UK溶栓组表达的程度明显高于缺血对照组;假手术组无MMP-9的表达。结论(1)缺血能导致MMP- 9的表达。(2)UK溶栓引起MMP-9表达的上调。     

Keratin 13基因在喉癌发生中的作用

探讨keratin 13基因在喉癌发生中的作用。方法在keratin 13基因内部及附近选择5个微卫星引物进行LOH分析，于DNA水平间接检测100例喉癌患者中该基因的缺失情况。结果5个STR位点均存在LOH，其中D17S1964E、D17S2092、D17S791、D17S1665及D17S808位点的LOH频率分别为30．48％、26．02％、21．62％、37．66%和21．51％，以D17S1665位点的LOH频率最高，杂合性丢失与临床分期无显著相关。结论Keratin13基因在喉癌的发生中具有重要作用，具体机制有待进一步研究。     

基质金属蛋白酶与肺癌转移的关系

基质金属蛋白酶(matrix metalloproteinases，MMPs)是一组锌离子依赖的蛋白水解酶，在ECM降解中起着重要作用。目前研究表明，MMPs活性异常不仅能促进肿瘤血管形成，还是人类多种肿瘤侵袭和转移的必要条件。本文就与肺癌侵袭和转移有关的MMPs研究作一综述。     

PTEN与基质金属蛋白酶在胃癌组织中的表达及意义

目的:探讨PTEN与基质金属蛋白酶(MMP)在胃癌组织中的表达、相互关系及意义。方法:应用免疫组化SP技术检测80例胃癌组织中PTEN、MMP2和MMP9表达,同时检测20例正常对照组胃粘膜中PTEN表达。结果:胃癌组织中PTEN高表达率35／80(43.8％)显著低于对照组20／20(100. 0％)(P<0.01);PTEN表达与胃癌分化程度、浸润深度、淋巴结转移和肿瘤分期显著相关;胃癌组织中 MMP2、MMP9阳性表达率分别为41／80(51.3％)、29／80(36．3％),与胃癌浸润深度、淋巴结转移和肿瘤分期显著相关;PTEN与MMP2、MMP9表达显著负相关,与病人预后相关,Kaplan-Meier生存曲线分析显示PTEN高表达者术后累计生存率显著高于低表达者,PTEN高表达者术后3年、5年生存率显著高于低表达者;MMP2、MMP9阳性表达者术后累计生存率显著低于阴性表达者,MMP2、MMP9阳性表达者术后3年、5年生存率显著低于阴性表达者。结论:胃癌组织中PTEN表达显著减少,PTEN 与MMP2、MMP9表达显著负相关,PTEN可能通过调控胃癌组织MMP2、MMP9表达,抑制胃癌的浸润和转移,影响病人的预后。     

支气管哮喘患者白细胞介素4和白细胞介素13测定的临床意义

目的:探讨血清中白细胞介素4(IL-4)和白细胞介素13(IL-13)在支气管哮喘发病中的作用.方法:本研究对临床确诊的支气管哮喘46例,与正常对照组46例,分别抽取血清采用 ELISA 法测定其 IL-4、IL-13的含量.结果:支气管哮喘急性发作期病人和对照组正常人血清中的 IL-4水平分别为(460.84±27.11)和(132.97±24.66) ng/L,二组经 t 检验后 P＜0.001.两组 IL-13 的水平分别为(23.76±5.44)和(12.61±2.49) ng/L,二组经 t 检验后 P＜0.001.结论:哮喘病人 IL-4、IL-13 明显高于对照组,提示 IL-4、IL-13 对哮喘发病有一定的调控作用,对支气管哮喘气道非特异性炎症和局部免疫反应起重要作用.