Expressions of cyclooxygenase-2 and matrix metalloproteinase-9 in cervical carcinoma and their clinical significance

Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detect the expres- sions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE). The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results: The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% (64/72) in group ICC and 12.5% (2/16) in group NCE, P = 0.000; MMP-9: 94.4% (68/72) in group ICC and 43.8% (7/16) in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis (r = 0.296, P = 0.012) and stromal invasion (r = 0.257, P = 0.029). The expression of MMP-9 was positively correlated with FIGO stage (r = 0.329, P = 0.005) and histological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). Conclusion: The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.

Expressions and clinical significances of MMP-2 and TIMP-2 mRNA in bladder transitional cell carcinomas

Objective:The aim of the study was to investigate the expressions of matrix metalloproteinase-2(MMP-2) and tissue inhibitor of MMP-2(TIMP-2) mRNA in transitional cell carcinomas of bladder and discuss their clinical significances.Methods:Using RT-PCR and real time quantitative PCR(RQ-PCR) technique,the expressions of MMP-2 and TIMP-2 mRNA of 45 cases of bladder carcinoma(tumor group) and 10 cases of normal bladder tissue(control group) were analyzed.Results:MMP-2 and TIMP-2 were not expressed in control group.MMP-2 was expressed in 30 cases tumor samples and TIMP-2 was expressed in 26 cases.The expression of MMP-2 mRNA in non-muscle invasive bladder cancers and grade I cancers was lower than that in muscle invasive bladder cancers and grades II-III cancers respectively.The differences were statistically significant(P<0.05).The expression of MMP-2 in recurrent patients was higher than that in incipient patients.TIMP-2 mRNA expression decreased with grades and stage.The expression of TIMP-2 in non-muscle invasive bladder cancers and grade I cancers was higher than that in muscle invasive bladder cancers and grades II-III cancers respectively.There was statistical difference between two groups(P < 0.05).TIMP-2 expression in incipient patients was higher than that in recurrent patients,but the difference was not significant(P>0.05).Conclusion:These results suggest that MMP-2 and TIMP-2 play an important role in the invasion step of transitional cell carcinoma of bladder.MMP-2 may become a new approach to the diagnosis of bladder carcinoma.

COX-2和MMP-2蛋白的表达对肺癌预后的影响

背景与目的:研究发现,环氧合酶-2(cyclooxygenase-2,COX-2)和基质金属蛋白酶-2(matrixmetalloproteinase-2,MMP-2)蛋白在肿瘤组织中的表达多有增高,而实验和临床研究提示,这两种蛋白的抑制剂可抑制肿瘤的生长、发展。本研究旨在探讨COX-2和MMP-2蛋白在人肺癌组织中的表达及其对患者预后的影响。方法:应用免疫组化方法检测42例肺癌组织中COX-2和MMP-2蛋白的表达情况,通过生存曲线法比较阳性组和阴性组患者的预后情况。结果:COX-2和MMP-2蛋白的阳性率分别为31%和62%;COX-2蛋白阳性组患者的生存期明显较阴性组短(P=0.019);MMP-2蛋白阳性组淋巴结癌转移的发生率明显较阴性组高(P=0.009),而患者生存期则明显较阴性组短(P=0.001);COX-2蛋白与MMP-2蛋白的表达之间无相关性(P=0.257)。结论:COX-2和MMP-2蛋白的表达与肺癌患者的预后相关,其高表达提示患者预后不良。

VEGF、COX-2、MMP-9在乳腺癌组织中的表达对乳腺钼靶X线征象的影响

目的探讨乳腺癌组织中血管内皮细胞生长因子(VEGF)、环氧化酶-2(COX-2)、基质金属蛋白酶-9(MMP-9)的表达对乳腺钼靶X线征象的影响,并初步探讨乳腺钼靶X线征象与分子病理学之间的关系。方法收集经乳腺钼靶X线检查、手术和病理证实的乳腺癌患者69例,将乳腺钼靶X线征象分为毛刺征、钙化征、异常血管征、淋巴结转移征,分析VEGF、COX-2、MMP-9表达对以上征象的影响。结果乳腺钼靶X线征象有毛刺征组VEGF、COX-2、MMP-9阳性表达率明显高于无毛刺征组(P<0.05);钙化组与无钙化组VEGF、COX-2、MMP-9阳性表达率差异无统计学意义(P>0.05);有异常血管征组VEGF、COX-2、MMP-9阳性表达率明显高于无异常血管征组(P<0.05);有淋巴结转移征组VEGF、COX-2、MMP-9阳性表达率明显高于无淋巴结转移征组(P<0.05)。结论 VEGF、COX-2、MMP-9高表达对乳腺钼钯X线征象毛刺征、异常血管征、淋巴结转移征的出现存在影响,并可作为乳腺钼钯X线恶性征象的生物学基础。

Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine

Objective： To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 （MMP-2） and tissue inhibitors of matrix metalloproteinase-2 （TIMP-2） and on cell migration of cultured rat vascular smooth muscle cells （VSMCs）. Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. Methods： Rat VSMCs were incubated with different concentrations of homocysteine （50-5000 μmol/L）. Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin （10^-9-10^-5 mol/L） were added when VSMCs were induced with 1 000 pmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. Results： Homocysteine （50-1000 μmol/L） increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 pmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and ac- tivation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine （50-5000 μmol/L） stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. Conclusions： Homocysteine （50-1000 μmol/L） significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and acti- vation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.

三七总皂苷对脑缺血再灌注损伤大鼠缺氧诱导因子1α和基质金属蛋白酶表达的影响

目的观察三七总皂苷(PNS)对脑缺血再灌注损伤大鼠血脑屏障损伤相关蛋白缺氧诱导因子1α(HIF-1α)、基质金属蛋白酶(MMP)-2和MMP-9表达的影响。方法选择SD大鼠130只,分为PNS组(60只)、模型组(60只)和假手术组(10只),PNS组于再灌注后给予尾静脉注射PNS 18mg/(kg·d),模型组和假手术组以等体积生理盐水替代。观察PNS组和模型组大鼠7d存活率。再灌注24h取材(每组10只),以脑组织HE和尼氏染色观察缺血半暗带神经元形态以及核心区神经元存活数,以ELISA法检测半暗带皮质HIF-1α、MMP-2及MMP-9蛋白表达水平。结果模型组神经元数量较假手术组明显减少[(190.0±59.4)个/mm2 vs(582.5±31.2)个/mm2,P<0.01];PNS组神经元数量较模型组显著增加[(372.5±41.1)个/mm2 vs(190.0±59.4)个/mm2,P<0.01]。模型组缺血再灌注24h MMP-2、MMP-9和HIF-1α水平显著高于假手术组(P<0.05,P<0.01);PNS组缺血再灌注24h MMP-2、MMP-9和HIF-1α水平显著低于模型组,差异有统计学意义(P<0.01)。结论 PNS对短暂性大脑中动脉闭塞模型大鼠缺血再灌注损伤早期起到神经元保护作用。

银杏叶提取物在高糖环境下对人视网膜微血管内皮细胞的作用及可能机制

目的研究不同浓度的银杏叶提取物(Ginkgo biloba extract,GBE)在高糖环境下对人视网膜微血管内皮细胞(human retinal capillary endothelial cells,HRCEC)的作用及对基质金属蛋白酶2(matrix metalloproteinase-2,MMP2)和核转录因子κB(nuclear transcription factor kappaB,NF-κB)p65表达的影响,为糖尿病视网膜病变的药物防治提供新的思路和理论依据。方法体外原代培养HRCEC,并通过免疫细胞化学方法鉴定;用GBE作用于原代培养的HRCEC,实验分为空白对照组、低糖对照组、高糖对照组、高糖+不同浓度GBE(12.5 mg·L-1、25.0 mg·L-1、50.0 mg·L-1、100.0 mg·L-1)组,分别使用MTT比色法观察其对细胞增殖的影响,使用免疫细胞化学及Western blotting检测药物作用前后HRCEC中MMP2及NF-κB p65的表达。结果 TT比色法结果显示,用不同浓度的GBE处理高糖(25.0 mmol·L-1)环境下HRCEC,作用24 h、48 h和72 h,高糖+不同浓度GBE对HRCEC增殖有促进作用,并存在时间和浓度的依赖性。高糖+不同浓度(12.5 mg·L-1、25.0 mg·L-1、50.0 mg·L-1、100.0 mg·L-1)GBE组作用24 h细胞增殖率分别为(16.4±0.7)%、(30.6±0.8)%、(41.3±1.5)%、(52.6±1.8)%,作用48 h细胞增殖率分别为(21.8±1.2)%、(36.2±1.3)%、(48.0±1.4)%、(62.7±1.6)%,作用72 h细胞增殖率分别为(29.9±0.5)%、(46.2±0.8)%、(61.2±0.8)%、(73.4±1.6)%。随着药物浓度的逐渐提高和作用时间的增加,细胞存活率逐渐提高,而细胞抑制率逐渐下降。用不同浓度的GBE处理HRCEC,作用72 h,行免疫细胞化学检测MMP2的表达,运用Western blotting检测NF-κB p65的表达,发现随着GBE药物浓度的增高,高糖环境下HRCEC中的MMP2、NF-κB p65表达量逐渐减少(P<0.05)。结论 GBE可以保护高糖环境下HRCEC并下调MMP2、NF-κB p65的表达,可用于糖尿病视网膜病变的防治。

基于χ~2准则的磁梯度张量3D聚焦反演方法

针对铁磁性物质反演中正则化参数自适应选择的问题,提出了基于χ~2准则的磁梯度张量3D聚焦反演方法。利用深度加权矩阵和最小支撑矩阵对经典Tikhonov正则化理论框架下的反演模型进行约束得到目标函数,避免了由于反演参数多于采集点数而导致反演解的多解性,并有效解决了核函数随深度增大而快速衰减的问题。通过对目标函数进行迭代奇异值分解获得最佳物性参数,并根据χ~2准则自适应地确定目标函数在迭代过程中的正则化参数,提高了迭代速度和求解精度。仿真和实验结果表明：该方法能准确还原磁性异常体的轮廓形态,具有较好的模型分辨率。

程氏分清方治疗阿霉素大鼠肾病综合征的实验研究

目的研究程氏分清方治疗阿霉素大鼠肾病综合征的作用机制。方法选取雄性SD健康大鼠40只,随机分为正常对照组、模型对照组、程氏分清方治疗组、程氏分清方联合泼尼松治疗组,每组各10只。采用1次性尾静脉注射盐酸阿霉素(5.5 mg/kg)的方法建立大鼠肾病综合征模型,并给予相应药物,观察各组对肾病综合征大鼠尿蛋白、白蛋白(Alb)、尿素氮(BUN)、血清肌酐(Cr)、三酰甘油(TG)、可溶性白细胞介素2受体(sIL-2R)、超氧化物歧化酶(SOD)、丙二醛(MDA)、基质金属蛋白酶(MMP-9)的影响。结果各治疗组均能明显降低肾病大鼠尿蛋白(P均<0.01);降低TG、MDA sIL-2R的浓度(P均<0.05)。各治疗组均能提高肾病大鼠Alb的含量,增强SOD活性,提高MMP-9的表达(P均<0.01)。结论程氏分清方可增强细胞免疫功能,提高抗氧化能力,清除氧自由基及其代谢产物,减少肾小球细胞外基质沉积,减轻肾小球病理改变。