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1.
目的探讨血清基质金属蛋白酶(MMP)-1、MMP-2、组织金属蛋白酶抑制因子(TIMP)-1与女性年龄、骨密度(BMD)及骨转换生化指标之间的关系。方法用ELISA测定591名20~80岁女性的血清MMP-1、MMP-2、TIMP-1、骨碱性磷酸酶(BAP)、骨钙素(OC)和Ⅰ型胶原氨基末端肽(NTX)水平,用双能X线骨密度仪测定多骨骼部位的BMD。结果(1)MMP-1、MMP-2、TIMP-1与年龄呈正相关(均P<0.01)。(2)按是否绝经分组结果表明:绝经后妇女MMP-2水平较绝经前妇女高[(1272±279)μg/L与(1141±290)μg/L,P<0.01]。(3)MMP-2与BMD呈负相关(P<0.05),但多元线性回归分析表明MMP-2不是BMD的预测因子。(4)MMP-2与血清BAP、OC、NTX正相关(均P<0.01)。(5)绝经后骨质疏松症患者血清MMP-2水平高于年龄匹配的正常对照组、骨量减少组[(1466±313,1222±243,1282±220)μg/L,均P<0.01]。结论血清MMP-2与骨转换生化指标相关联。血清MMP-2水平升高可能为高骨代谢转换过程(如绝经后骨质疏松症)中的一种伴随表现。  相似文献   

2.
目的通过检测冠心病患者核转录因子过氧化物酶体增殖体激活受体γ(PPARγ) mRNA表达和血浆基质金属蛋白酶-9(MMP-9)水平,探讨PPARγ对冠心病的影响。方法经冠状动脉造影确诊的冠心病患者(冠心病组)153例,RT-PCR法测定外周血中PPARγmRNA表达,ELISA法检测血浆中MMP-9含量,并对冠状动脉病变程度进行分型,分析PPARγmRNA表达、MMP-9与冠状动脉病变程度的相关性。结果冠心病组PPARγmRNA表达(0.40±0.12)与对照组(0.62±0.13)比较显著降低;冠心病组MMP-9为(1.27±0.16)μg/L,与对照组[(1.21±0.05)μg/L]比较明显增加(P<0.01)。冠心病组中急性冠状动脉综合征患者PPARγ为(0.50±0.05),较稳定性心绞痛(0.50±0.11)降低,MMP-9分别为(1.38±0.14)、(1.25±0.07)μg/L,P<0.01。PPARγmRNA表达分别与冠状动脉病变支数(r=-0.42,P<0.01)、病变类型(r=-0.56,P<0.01)呈负相关,MMP-9水平则与病变支数(r=0.30,P<0.01)、病变类型(r=0.36,P<0.01)呈正相关;PPARγmRNA表达和MMP-9水平呈负相关。结论MMP-9对急性冠状动脉综合征患者不稳定斑块有促进作用,PPARγ具有抑制MMP-9的作用,提示通过激活PPARγmRNA表达和降低MMP-9水平对冠心病高危人群具有保护作用。  相似文献   

3.
目的观察关节腔内注射脱氢表雄酮(DHEA)对兔骨关节炎的影响,并探讨其作用机制。方法40只新西兰大白兔行单侧前交叉韧带切除术,术后4周随机分为实验组和对照组。实验组关节腔内注射100μmol/L DHEA(DHEA溶于二甲基亚砜),每周1次,连续5周;对照组注射同剂量的二甲基亚砜。术后9周处死兔子,取膝关节行大体和组织病理学检查,用反转录聚合酶链反应(RT-PCR)方法检测关节软骨及滑膜中基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶组织抑制因子-1(TIMP-1)和白细胞介素-1β(IL-1β)mRNA的表达。结果大体和组织病理学检查显示实验组软骨和滑膜病变程度轻于对照组。实验组软骨和滑膜中MMP-3 mRNA的表达水平显著低于对照组(均P<0.05),而TIMP-1 mRNA的表达显著高于对照组(均P<0.05)。实验组软骨IL-IβmRNA的表达与对照组表达差异无统计学意义(P>0.05),而滑膜IL-1βmRNA的表达显著低于对照组(P<0.01)。结论DHEA对兔软骨有修复和保护的作用,减轻滑膜的炎症,能够延缓骨关节炎的进展。下调软骨、滑膜MMP-3和上调软骨、滑膜TIMP-1的表达及下调滑膜IL-1β的表达可能是DHEA对骨关节炎的作用机制。  相似文献   

4.
目的研究不同浓度雌二醇(E_2)对去卵巢小鼠脾细胞雌激素受体(ER)及辅助性T细胞1(Th1)和辅助性T细胞2(Th2)之间平衡的影响。方法将小鼠脾细胞分为7组:青年组、假手术组、去卵巢对照组及去卵巢+E_2(10~(-11)mol/L、10~(-10)mol/L、10~(-9)mol/L、10~(-8)mol/L)组。逆转录-聚合酶链反应(RT-PCR)方法检测ERα、ERβmRNA的表达;酶联免疫吸附法(ELISA)法检测细胞因子干扰素-γ(IFN-γ)、白细胞介素-2(IL-2)和白细胞介素-4(IL-4)水平,以了解Th1与Th2的平衡关系。结果去卵巢对照组ERα、ERβmRNA水平分别为0.68±0.15和0.70±0.17,较青年组(0.95±0.21和0.93±0.1 9)及假手术组(0.98±0.28和0.94±0.20)下降(P<0.05和P<0.01);去卵巢+E_2(10~(10)mol/L)组ERα、ERβ的表达分别为0.95±0.19和0.90±0.29,较去卵巢对照组升高(P<0.05和P<0.01)。去卵巢对照组IFN-γ、IL-2分别为(360.36±8.64)ng/L和(1485.49±5.01)ng/L,较青年组[(93.46±4.81)ng/L和(704.37±5.32)ng/L]及假手术组[(92.47±2.95)ng/ L和(716.84±1 6.48)ng/L]升高(均为P<0.01);而去卵巢对照组IL-4水平[(258.11±6.00)ng/L]低于青年组[(269.77±8.44)ng/L]和假手术组[(270.18±10.34)ng/L](均为P<0.05)。去卵巢+ E_2(10~(10)mol/L)组的IFN-γ、IL-2分别为(94.05±7.17)ng/L和(712.15±13.84)ng/L,低于去卵巢对照组(均为P<0.01),IL-4为(269.76±2.05)ng/L,高于去卵巢对照组(P<0.05)。结论不同浓度E_2对去卵巢小鼠脾细胞ERα、ERβ基因表达起不同的调节作用:在生理范围内为正向调节,超生理范围为负向调节。小鼠去卵巢后影响脾细胞Th1和Th2的平衡,表现为Th1漂移。生理浓度的E_2能部分逆转Th1漂移,部分恢复Th1和Th2的平衡。  相似文献   

5.
目的探讨LQT1患者在交感神经兴奋时发生室性心律失常的机制。方法实验切取犬楔形心室肌组织块,用30μmol/L chromanol 293B(I_(Ks)阻断剂)灌流该标本模拟LQT1,采用玻璃微电极和特制的金属电极,同步记录造模前后的中层和外层心室肌细胞的跨膜动作电位(TAP)和跨壁心电图(TECG),并观察异丙肾上腺素(Iso,100 nmol/L)对造模后的TAP和TECG的影响。结果chro- manol 293B使中层和外层心室肌细胞动作电位时限(APD_(90))均匀延长[中层:(287±12)ms vs(362±18)ms,P<0.05;外层:(229±13)ms vs(303±20)ms,P<0.05],跨壁复极离散度(TDR)增加不明显[(46±5)ms v8(49±7)ms,P>0.05],TECG示QT间期延长[(314±13)ms vs(389±16)ms,P<0.05]。加入Iso后,中层心室肌细胞APD_(90)延长[(362±18)ms vs(388±14)ms,P<0.05],并出现早期后除极(EAD),外层心室肌细胞APD_(90)缩短[(303±20)ms vs(285±12)ms,P<0.05],TDR明显增加[(49±7)ms vs(87±11)ms,P<0.05],TECG示QT间期延长[(389±16)ms vs(405±15) ms,P<0.05],并能自发产生室性早搏和室性心动过速。结论在LQT1模型中,Iso对中层和外层心室肌细胞TAP的影响不一致,引起TDR增加,这可能是交感神经兴奋使LQT1患者发生室性心律失常的机制。  相似文献   

6.
目的 探讨人基质金属蛋白酶组织抑制物-1(tissue inhibitor of metalloproteinase-1,TIMP-1)对肾脏器官衰老过程血管生成的影响。方法 对3、12、24月龄人TIMP-1转基因小鼠和野生型小鼠肾组织石蜡切片行PASM染色,观察肾组织内微血管密度变化;Western免疫印迹检测TIMP-1、TIMP-2、基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9、血管内皮细胞生长因子(VEGF)、Ⅲ型和Ⅳ型胶原蛋白质表达;明胶酶谱和反向酶谱分别检测明胶酶和TIMP-1的活性。结果 24月龄时与野生型小鼠相比,转基因小鼠肾小球和肾小管周围的微血管密度降低(P〈0.05);TIMP-1、Ⅲ型和Ⅳ型胶原蛋白质表达增多(P〈0.05),而MMP-2、MMP-9和VEGF的表达降低(P〈0.05);明胶酶谱和反向酶谱结果显示,明胶酶的活性下调(P〈0.05),而TIMP-1的活性则上调(P〈0.05)。结论 TIMP-1可能通过影响血管生成而促进肾脏器官衰老。 基金 国家重点基础研究发展规划(973项目,2007CB507403);; 国家自然科学基金创新群体科学基金(30121005)  相似文献   

7.
Objective To investigate the effects of smoking and smoking cessation on airway inflammation and remodeling in chronic obstructive pulmonary diseases through detecting mRNA and protein expressions of nuclear factor-κB (NF-κB), cell matrix metalloproteinase-9 (MMP-9) and cellular tissue inhibitor of metalloproteinase-1 (TIMP-1) in airway epithelial cells of smoking and smoking cessation rats. Methods Twenty-four male Wistar rats were randomly divided into control group, smoking group and smoking cessation group,eight in each group. Hybridization in situ and immunohistochemistry were used to detect mRNA and protein expressions of NF-κB, MMP-9 and TIMP-1 in airway epithelial cells of rats. Results ① Compared with control group (0.29 ± 0.06,0.29±0.06), mRNA and protein expressions of NF-κB in smoking group (0.45±0.04,0.41±0.03) and smoking cessation group (0.40±0.05,0.37±0.03) were higher (all P<0.05). The mRNA and protein expressions of NF-κB in smoking cessation group were lower than those in smoking group (all P <0.05). ②Compared with control group (0.30±0.06,0.30±0.06) ,mRNA and protein expressions of MMP-9 in smoking group (0.52±0.03,0.51±0.07) and smoking cessation group (0.38±0.03,0.33±0.02) were higher (all P<0.05). The mRNA and protein expressions of MMP-9 in smoking cessation group were lower than those in smoking group (all P<0.05). ③Compared with control group (0.26±0.04, 0.26±0.04), mRNA and protein expressions of TIMP-1 in smoking group (0.49±0.05,0.37±0.03) and smoking cessation group (0.42±0.04,0.35±0.03) were higher (all P <0.05). The mRNA and protein expressions of TIMP-1 in smoking cessation group were lower than those in smoking group (all P < 0.05). ④ Compared with control group (1.00±0.02,1.00±0.02), MMP-9/TIMP-1 mRNA and protein expressions were larger than one in smoking group (1.07±0.14, 1.37±0.19), and less than one in smoking cessation group (0.92±0.13,0.94±0.10) (all P <0.05). ⑤The mRNA and protein expressions of NF-κB and MMP-9in each group were positively correlation (r=0.87,0.66,all P <0.05). Conclusions In airway epithelial cells of smoking rats, mRNA and protein expressions of NF-κB, MMP-9 and TIMP-1 increase, and MMP-9/TIMP-1 is larger than one. After stoping smoking, mRNA and protein expressions of NF-κB,MMP-9 and TIMP-1 decrease, and MMP-9/TIMP-1 is less than one. This experiment explains that smoking can cause airway inflammation and remodeling, smoking cessation can reduce airway inflammation and remodeling.  相似文献   

8.
目的观察高脂高热量饲料长期饲养对大鼠胰岛形态功能的影响,探讨其与外周胰岛素抵抗的关系。方法8周龄雄性Wistar大鼠30只,分为正常对照组(NC,n=15)和高脂饲养组(HF,n=15),分别给予普通饲料和高脂高热量饲料饲养,采用高胰岛素-正常血糖钳夹技术测定外周胰岛素抵抗程度;以静脉胰岛素释放试验观察胰岛分泌功能;作胰岛素和胰高血糖素双重免疫组化染色,进行胰岛形态学及量化分析;RT-PCR观察胰岛素原mRNA水平的变化。结果HF组的葡萄糖输注率(GIR)显著低于NC组[(5.83±0.79)mg·kg~(-1)·min~(-1)vs(7.60±1.29)mg·kg~(-1)·min~(-1),P<0.05]。胰岛的免疫组化结果显示HF组单个胰岛的体积增大[(15168±1327)μm~2 vs(6264±1840)μm~2,P<0.01],β细胞相对于α细胞比率下降[(4.68±1.01)vs(11.84±3.82),P<0.05],β细胞的胰岛素相对浓度降低[(-5.15±0.03) vs(-4.81±0.17),P<0.01]。HF组胰岛素分泌高峰明显延迟至10min,NC组达峰时间为5min,HF组胰岛素曲线下面积在10~60min则显著增高[(152.51±34.53)mIU·L~(-1)·min~(-1)vs(86.40±21.21)mIU·L~(-1)·min~(-1),P<0.01],60 min胰岛素仍在基础水平之上,胰岛素原mRNA差异无统计学意义。结论长期高脂高热量饮食不仅诱导出显著的胰岛素抵抗,胰岛的形态和功能已经出现了早期的损害,提示在2型糖尿病发生发展的前期阶段胰岛的代偿能力已经受损。  相似文献   

9.
邹强  鲍健  吴正升  齐越  吴强  杨枫 《山东医药》2008,48(24):12-14
目的 探讨基质金属蛋白酶(MMP)-2及其抑制物(TIMP-2)与转化生长因子(TGF)-β1及其Ⅰ型受体(TGF-β1RⅠ)在乳腺癌组织中的表达及其相关性.方法 应用免疫组化SP法检测80例乳腺癌组织中的MMP-2、TIMP-2与TGF-β1、TGF-β1RⅠ蛋白.结果 乳腺癌中MMP-2、TIMP-2、TGF-β1和TGF-β1RⅠ阳性表达率分别为67.5%、45.0%、80.0%和67.5%;无淋巴结转移者MMP-2、TIMP-2阳性表达率为44.4%、66.7%,与转移淋巴结个数1~3(85.7%、21.4%)、>3个(87.5%、37.5%)相比,P均<0.01;TNM分期为Ⅰ期的MMP-2、TIMP-2阳性表达率分别为0、75%,分别与Ⅱ(65.0%、55.0%)、Ⅲ(86.7%、26.7%)、Ⅳ期(100%、0)相比,P均<0.05;肿瘤直径≤2 cm者TIMP-2阳性表达率为66.7%,与直径2~5(51.9%)、>5 cm(20.0%)相比,P均<0.05;MMP-2和TGF-β1的表达呈正相关(r=0.454,P<0.01),MMP-2和TGF-β1RⅠ的表达呈负相关(r=-0.481,P<0.01).结论 MMP-2和TIMP-2的表达情况与乳腺癌侵袭转移有密切关系.MMP-2的表达与TGF-β1、TGF-β1RⅠ关系密切,MMP-2可能在一定程度上受到TGF-β1及其受体的调控.  相似文献   

10.
张燕  张祥盛  赵大华 《山东医药》2006,46(22):44-45
采用免疫组化S-P法检测52例肾透明细胞癌明胶酶A(MMP-2)、金属蛋白酶2组织抑制剂(TIMP-2)表达情况,结果浸润被膜和淋巴结转移组肾透明细胞癌MMP-2的表达明显高于无被膜浸润和无淋巴结转移组(P〈0.05)IMMP-2与肿瘤浸润和淋巴结转移呈正相关,而TIMP-2与其呈负相关(P〈0.05)。表明MMP-2、TIMP-2可作为肿瘤进展及估计预后的参考指标。  相似文献   

11.
The immunoneuroendocrine role of melatonin   总被引:19,自引:0,他引:19  
Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.  相似文献   

12.
13.
Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.  相似文献   

14.
Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.  相似文献   

15.
Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.  相似文献   

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Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the Mr range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [125I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (Ka of 4.7 ± 0.2 × 109 M-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of Mr 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.  相似文献   

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PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.  相似文献   

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