特发性肺纤维化和结节病患者基质金属蛋白酶的变化及其临床意义

Objective To detect the levels of matrix metalloprotease(MMP)-1 and MMP-7 in the serum and the bronchoalveolar lavage fluid(BALF)of patients with idiopathic pulmonary fibrosis(IPF)and sarcoidosis(Stage Ⅱ),and therefore to investigate the significance of these changes in the pathogenesis of IPF. Methods Forty-four clinically confirmed cases of IPF were recruited,with the patients'age ranging from 46 to 70 years(58±9 years).Twenty patients with sarcoidosis,aged 35 to 65(50±12)years,were also studied.Enzyme-linked immunoabsorbent assay was used to detect the levels of MMP-1 and MMP-7 in the serum and the BALF samples. Results In the serum of patients with IPF,the level of MMP-1 [3.78 (0.14-13.44) μLg/L]was lower than that in patients with sarcoidosis[7.79(4.67-10.68)μg/L(z=-3.53,P<0.01)],but the level of MMP-7[7.83(3.57-14.37) μg/L]was higher than that in patients with sarcoidesis[4.04(0.06-9.94)μg/L(z=-3.84,P<0.01)].In the BALF of patients with IPF,the level of MMP-1 [1.09(0.04-5.14)μg/L]was lower than that in patients with sarcoidosis [2.08(0,05-4.16)μg/L(z=-1.53,P>0.05)],but the level of MMP-7[3.75(1.10-9.87)μg/L]was highet than that in patients with sarcoidosis[1.16(0.02-4.47)μg/L(x=-5.33,P<0.01)].The serum level of MMP-7 in patients with IPF was negatively correlated with the diffusing capacity of carbon monoxide(r=-0.56,P<0.01)and the percentage of neutrophils(r=-0.47,P<0.01).The level of MMP-7 in the BALF showed a negative correlation with diffusing capacity of carbon monoxide(r=-0.31,P <0. 05). Conclusions The results suggest that MMP-1 may be increased in the inflammatory phase as compared to the matrix remodeling phase of lung fibrosis, while MMP-7 may be increased in the matrix remodeling phase rather than in the inflammatory phase. MMP-7 may act as an important indicator for the severity of IPF.     

The clinical relevance of MBL2 gene polymorphism and sepsis

Objective:To detect the clinical relevance of mannose-binding lectin 2(MBL2) gene polymorphism and sepsis in Chinese lived in Hainan island.Methods: Blood samples from 57 patients with sepsis and 69 patients without sepsis were collected in the ICU of several large hospitals in Hainan province. Genomic DNA was extracted from whole blood and then PCR purification product was sequenced and typed by 3730 sequencing analyzer. The concentration of MBIL2 in serum was detected by ELISA.Results: We found that genotype and allele distributions in two groups were in accordance with the Hardy-Weinberg Equilibrium. The frequency of GA genotype was significantly higher than that in non-sepsis group(P=0.013). A allele frequency in sepsis group was also much higher than that in non-sepsis group(P=0.028).Logister regression analysis showed that the patients who carried A allele were more prone to get sepsis than G allele carrier(P=0.014, OR=2,550, 95%CI=1.207-5.386). The MBL2 level in serum of sepsis patients with genotype GG and GA was significantly lower than that in non-sepsis group(P0.05). In sepsis group, the MBL2 serum level of patients with genotype GA was obviously lower than that in patients with genotype GG(P0.05).Conclusions: The variation of rs 1800450 G→A increased the incidence of sepsis and decreased the level of MBL2 in serum.     

UNCLASSIFIED DISORDER

(non一smokers).Results:The levels of TNFa(11.9士3.2、11.7士3 .0 ng·L一’,and NCF(1 91士51、203士44 eell·loHP一‘)ofBALF in the patienrs wirh sareoidosis and IPF were signifi-eantlyh:gher than those in eontrol grouP(P<0.01)and wereh igher than those in serurn.The level of TNF一a in the BALF ofPatients with sareoidosis was Posirively eorrelated with thepereenrage of lymphoeytes(r=0.73,P<0.01).The aetivity ofNCF in the BALF of patients with IPF was Positively eorrelat-ed with th…     

凋亡抑制蛋白Livin在非小细胞肺癌患者血清中的表达

Objective To investigate the clinical significance of Livin in the diagnosis of non-small cell lung cancer (NSCLC) through testing the content of inhibitor of apoptosis protein Livin in the serum of NSCLC patients, pneumonia patients and healthy persons. Methods Livin levels in the serum of 85 NSCLC patients, 20 pneumonia patients and 20 healthy persons were detected by enzyme linked immunosorbent assay. Results Livin level in the serum of NSCLC patients was significantly higher than that in pneumonia patients and healthy persons. The serum Livin level was increased following with tumor progress. Livin level in NSCLC patients with stage Ⅲ-Ⅳ was higher than that in NSCLC patients with stage Ⅰ - Ⅱ ( P ＜0.05) . Conclusions As an inhibitor of apoptosis protein,Livin has certain clinical value on the diagnosis and prognosis judgement of NSCLC patients.     

Expression of annexin A5 in serum and tumor tissue of patients with colon cancer and its clinical significance

AIM To investigate the expression of annexin A5 in serum and tumor tissue of patients with colon cancer and to analyze its clinical significance.METHODS Ninety-three patients with colon cancer treated at our hospital between February 2013 and March 2016 were included in an observation group, and 40 healthy individuals were included in a control group. Enzyme-linked immunosorbent assay was performed to determine the serum level of annexin A5, while immunohistochemistry was performed to determine the expression of annexin A5 in cancer tissues.RESULTS The serum level of annexin A5 was 0.184 ± 0.043 ng/m L in the observation group, which was significantly higher than that in the control group(P 0.05). Annexin A5 expression was detected in 79.31% of the patients with lymph node metastasis, which was significantly higher than that in patients without lymph node metastasis(P 0.05). Moreover, annexin A5 expression was detected in 86.96% of the patients with stage Ⅲ to Ⅳ disease, which was significantly higher than that in patients with stage Ⅰ to Ⅱ disease(P 0.05). The serum level of annexin A5 was 0.215 ± 0.044 ng/m L in patients whose tumors were positive for annexin A5 expression, which was significantly higher than that in patients whose tumors were negative for annexin A5 expression(P 0.05). The serum level of annexin A5 was correlated with annexin A5 expression in colon cancer tissues(r= 0.312, P 0.05). When a cutoff value of 0.148 ng/m L for serum level of annexin A5 was used in the diagnosis of colon cancer, the sensitivity was 83.90%, and the specificity was 57.50%.CONCLUSION For patients with colon cancer, annexin A5 expression in cancer tissues is related to lymph node metastasis and tumor grade. Serum level of annexin A5 is related to annexin A5 expression in cancer tissues and is of diagnostic relevance.     

Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

AIM:To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF).METHODS:Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine(Cr)level(<1.2 mg/dL in men,or<1.1 mg/dL in women)were enrolled in the Liver Failure Treatment and Research Center of Beijing 302 Hospital between August 2011 and October 2012.Thirty patients with chronic hepatitis B(CHB)and 30 healthy controls in the same study period were also included.Measurement of serum cystatin C(CysC)was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer system.The ACLF patients were followed during their hospitalization period.RESULTS:In the ACLF group,serum level of CysC was 1.1±0.4 mg/L,which was significantly higher(P<0.01)than those in the healthy controls(0.6±0.3mg/L)and CHB patients(0.7±0.2 mg/L).During the hospitalization period,eight ACLF patients developed AKI.Logistic regression analysis indicated that CysC level was an independent risk factor for AKI development(odds ratio=1.8;95%CI:1.4-2.3,P=0.021).The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/L.The baseline CysC-based estimated glomerular filtration rate(eGFR CysC)was significantly lower than the creatinine-based eGFR(eGFR CG and eGFR MDRD)in ACLF patients with AKI,suggesting that baseline eGFR CysC represented early renal function in ACLF patients while the Cr levels were still within the normal ranges.CONCLUSION:Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.     

老年原发性非小细胞肺癌患者外周血T细胞膜型和可溶性CD28的表达

Objective To explore the expression of membrane form of CD28 (mCD28) on T lymphoeytes and the serum level of soluble CD28 (sCD28) in elderly patients with primary non-small cell lung cancer (NSCLC) in order to investigate the relationship between age-related changes of CD28 and the development of NSCLC in elderly patients. Methods 63 elderly patients with NSCLC, 35 elderly patients with lung benign lesion, 30 elderly healthy donors, 30 young healthy donors, 20 young patients with lung benign lesion and 20 young patients with NSCLC were enrolled in this study. The mCD28 on T cells and the serum level of sCD28 were measured by four-color flow eytometric assay and enzyme linked immunosorbent respectively, and the relationship between CD28 and clinical characteristics of NSCLC was analysed Results The expression of mCD28 was decreased and the serum level of sCD28 was increased in elderly patients with NSCLC compared with the other groups (F= 184.25, P<0. 01 ; F= 365.40, P<0.01). The expression of mCD28 was significantly lower and the level of sCD28 was significantly higher in elderly healthy donors than those in young healthy donors and young patients with lung benign lesion (P<0. 05). There were no significantly statistical differences in expression of mCD28 and level of sCD28 between elderly healthy donors and elderly patients with lung benign lesion [(42.84±5.82)% vs. (46.09±-7.34)%, (39.38±6.02)μg/L vs. (35.84±5.02)μg/L, P>0. 05]. Logistic regression analysis showed that aging (OR=2. 432), down-regulation of mCD28 expression (OR=0. 876) and up-regulation of sCD28 level (OR= 1. 113) were the risk factors for lung cancer. In the elderly patients with NSCLC, there were significant differences in mCD28 expression and sCD28 level between stages Ⅲ-Ⅳ and stages Ⅰ-Ⅱ [(16. 51± 5.64)% vs. (24.41±8.24)%, (75.03±5.98) μg/L vs. (66.73±7.52)μg/L; t=4.497,4.794, both P <0. 01]. However, there were no significantly statistical differences among different pathological types (F=0. 609, 0. 302, both P > 0. 05). Conclusions The down-regulation of mCD28 expression and up-regulation of sCD28 level with advancing age play an important role in the oncogenesis and development of primary non-small cell lung cancer in the elderly patients.     

老年原发性非小细胞肺癌患者外周血T细胞膜型和可溶性CD28的表达

Objective To explore the expression of membrane form of CD28 (mCD28) on T lymphoeytes and the serum level of soluble CD28 (sCD28) in elderly patients with primary non-small cell lung cancer (NSCLC) in order to investigate the relationship between age-related changes of CD28 and the development of NSCLC in elderly patients. Methods 63 elderly patients with NSCLC, 35 elderly patients with lung benign lesion, 30 elderly healthy donors, 30 young healthy donors, 20 young patients with lung benign lesion and 20 young patients with NSCLC were enrolled in this study. The mCD28 on T cells and the serum level of sCD28 were measured by four-color flow eytometric assay and enzyme linked immunosorbent respectively, and the relationship between CD28 and clinical characteristics of NSCLC was analysed Results The expression of mCD28 was decreased and the serum level of sCD28 was increased in elderly patients with NSCLC compared with the other groups (F= 184.25, P<0. 01 ; F= 365.40, P<0.01). The expression of mCD28 was significantly lower and the level of sCD28 was significantly higher in elderly healthy donors than those in young healthy donors and young patients with lung benign lesion (P<0. 05). There were no significantly statistical differences in expression of mCD28 and level of sCD28 between elderly healthy donors and elderly patients with lung benign lesion [(42.84±5.82)% vs. (46.09±-7.34)%, (39.38±6.02)μg/L vs. (35.84±5.02)μg/L, P>0. 05]. Logistic regression analysis showed that aging (OR=2. 432), down-regulation of mCD28 expression (OR=0. 876) and up-regulation of sCD28 level (OR= 1. 113) were the risk factors for lung cancer. In the elderly patients with NSCLC, there were significant differences in mCD28 expression and sCD28 level between stages Ⅲ-Ⅳ and stages Ⅰ-Ⅱ [(16. 51± 5.64)% vs. (24.41±8.24)%, (75.03±5.98) μg/L vs. (66.73±7.52)μg/L; t=4.497,4.794, both P <0. 01]. However, there were no significantly statistical differences among different pathological types (F=0. 609, 0. 302, both P > 0. 05). Conclusions The down-regulation of mCD28 expression and up-regulation of sCD28 level with advancing age play an important role in the oncogenesis and development of primary non-small cell lung cancer in the elderly patients.     

老年原发性非小细胞肺癌患者外周血T细胞膜型和可溶性CD28的表达

Objective To explore the expression of membrane form of CD28 (mCD28) on T lymphoeytes and the serum level of soluble CD28 (sCD28) in elderly patients with primary non-small cell lung cancer (NSCLC) in order to investigate the relationship between age-related changes of CD28 and the development of NSCLC in elderly patients. Methods 63 elderly patients with NSCLC, 35 elderly patients with lung benign lesion, 30 elderly healthy donors, 30 young healthy donors, 20 young patients with lung benign lesion and 20 young patients with NSCLC were enrolled in this study. The mCD28 on T cells and the serum level of sCD28 were measured by four-color flow eytometric assay and enzyme linked immunosorbent respectively, and the relationship between CD28 and clinical characteristics of NSCLC was analysed Results The expression of mCD28 was decreased and the serum level of sCD28 was increased in elderly patients with NSCLC compared with the other groups (F= 184.25, P<0. 01 ; F= 365.40, P<0.01). The expression of mCD28 was significantly lower and the level of sCD28 was significantly higher in elderly healthy donors than those in young healthy donors and young patients with lung benign lesion (P<0. 05). There were no significantly statistical differences in expression of mCD28 and level of sCD28 between elderly healthy donors and elderly patients with lung benign lesion [(42.84±5.82)% vs. (46.09±-7.34)%, (39.38±6.02)μg/L vs. (35.84±5.02)μg/L, P>0. 05]. Logistic regression analysis showed that aging (OR=2. 432), down-regulation of mCD28 expression (OR=0. 876) and up-regulation of sCD28 level (OR= 1. 113) were the risk factors for lung cancer. In the elderly patients with NSCLC, there were significant differences in mCD28 expression and sCD28 level between stages Ⅲ-Ⅳ and stages Ⅰ-Ⅱ [(16. 51± 5.64)% vs. (24.41±8.24)%, (75.03±5.98) μg/L vs. (66.73±7.52)μg/L; t=4.497,4.794, both P <0. 01]. However, there were no significantly statistical differences among different pathological types (F=0. 609, 0. 302, both P > 0. 05). Conclusions The down-regulation of mCD28 expression and up-regulation of sCD28 level with advancing age play an important role in the oncogenesis and development of primary non-small cell lung cancer in the elderly patients.     

老年原发性非小细胞肺癌患者外周血T细胞膜型和可溶性CD28的表达

Objective To explore the expression of membrane form of CD28 (mCD28) on T lymphoeytes and the serum level of soluble CD28 (sCD28) in elderly patients with primary non-small cell lung cancer (NSCLC) in order to investigate the relationship between age-related changes of CD28 and the development of NSCLC in elderly patients. Methods 63 elderly patients with NSCLC, 35 elderly patients with lung benign lesion, 30 elderly healthy donors, 30 young healthy donors, 20 young patients with lung benign lesion and 20 young patients with NSCLC were enrolled in this study. The mCD28 on T cells and the serum level of sCD28 were measured by four-color flow eytometric assay and enzyme linked immunosorbent respectively, and the relationship between CD28 and clinical characteristics of NSCLC was analysed Results The expression of mCD28 was decreased and the serum level of sCD28 was increased in elderly patients with NSCLC compared with the other groups (F= 184.25, P<0. 01 ; F= 365.40, P<0.01). The expression of mCD28 was significantly lower and the level of sCD28 was significantly higher in elderly healthy donors than those in young healthy donors and young patients with lung benign lesion (P<0. 05). There were no significantly statistical differences in expression of mCD28 and level of sCD28 between elderly healthy donors and elderly patients with lung benign lesion [(42.84±5.82)% vs. (46.09±-7.34)%, (39.38±6.02)μg/L vs. (35.84±5.02)μg/L, P>0. 05]. Logistic regression analysis showed that aging (OR=2. 432), down-regulation of mCD28 expression (OR=0. 876) and up-regulation of sCD28 level (OR= 1. 113) were the risk factors for lung cancer. In the elderly patients with NSCLC, there were significant differences in mCD28 expression and sCD28 level between stages Ⅲ-Ⅳ and stages Ⅰ-Ⅱ [(16. 51± 5.64)% vs. (24.41±8.24)%, (75.03±5.98) μg/L vs. (66.73±7.52)μg/L; t=4.497,4.794, both P <0. 01]. However, there were no significantly statistical differences among different pathological types (F=0. 609, 0. 302, both P > 0. 05). Conclusions The down-regulation of mCD28 expression and up-regulation of sCD28 level with advancing age play an important role in the oncogenesis and development of primary non-small cell lung cancer in the elderly patients.     

MMP-2和MMP-9蛋白在结肠癌中的表达

目的:分析基质金属蛋白酶-2(MMP-2)和MMP-9蛋白与结肠癌病理因素的关系,探讨MMP蛋白在结肠癌发生中的临床意义.方法:用SP免疫组化法检测31例结肠癌中MMP-2和MMP-9蛋白表达情况,并用SPSS10.0forWindows软件统计分析MMP蛋白与临床病理因素的关系.以20例溃疡性结肠炎、21例结肠腺瘤和10例正常结肠黏膜作为对照组.结果:MMP-2除结肠癌组和正常结肠黏膜组间相比具有显著性差异(10.0%vs54.8%,P<0.05)外,其余各组间比较差异无统计学意义,MMP-9各组间比较差异无统计学意义,从溃疡性结肠炎、结肠腺瘤到结肠癌中MMP-2和MMP-9蛋白表达阳性率不同且具有递增趋势.MMP-2和MMP-9蛋白表达与结肠癌的Duke’s分期及有无淋巴结转移显著相关(A B期:38.9%和27.8%;C D期:76.9%和84.6%;无淋巴结转移:38.9%和27.8%;有淋巴结转移:76.9%和84.6%,P<0.05).结论:MMP-2和MMP-9蛋白过度表达对结肠癌的诊断、Duke's分期及有无淋巴结转移判断具有重要的临床意义.     

基质金属蛋白酶-2、基质金属蛋白酶-9与特发性肺纤维化的研究进展

基质金属蛋白酶是一组金属依赖的可降解细胞外基质的蛋白酶类.基质金属蛋白酶与基质金属蛋白酶组织抑制因子之间的比例失衡可能导致细胞外基质的降解异常,这可以促进纤维化的过程.近年来随着研究的进展,发现基质金属蛋白酶-2和基质金属蛋白酶-9与特发性肺纤维化有着密切的关系,现就此作一综述.     

基质金属蛋白酶在糖尿病患者动脉粥样硬化斑块中的表达

目的检测2型糖尿病患者动脉粥样硬化斑块内基质金属蛋白酶2(MMP2)和基质金属蛋白酶9(MMP9)的表达和分布,探讨MMP2和MMP9在糖尿病动脉粥样硬化斑块中表达的作用.方法从23例糖尿病足截肢和17例尸检下肢动脉标本中选取晚期动脉粥样硬化病变的组织126块,糖尿病组(74块),非糖尿病组(52块),从中随机选取各40块进行MMP2和MMP9抗原抗体的免疫组织化学染色,观察阳性物质在两组动脉粥样硬化斑块中的分布特点,利用计算机图像分析系统对染色程度作相对定量分析. 结果抗MMP2、抗MMP9免疫沉积物主要集中在斑块核心周围,特别是在斑块的肩部和纤维帽.糖尿病组动脉内膜抗MMP2免疫沉积物表达显著高于非糖尿病组[免疫沉淀物积分吸光度值(IA)69 014±14 459和57 004±16 171,阳性面积百分比(12.97±2.67)% 和(11.08±3.32)%,P<0.05];糖尿病组斑块内MMP9表达也显著高于非糖尿病组[IA 102 485±20 431和75 280±13 106,阳性面积百分比(18.35±3.59)%和(13.65±2.29)%,P<0.01]. 结论 MMP2和MMP9在糖尿病组动脉粥样硬化斑块中的表达显著高于非糖尿病组,MMP2和MMP9在糖尿病患者动脉中表达增强可以部分解释糖尿病患者易于发生动脉粥样硬化斑块破裂.     

microRNA对基质金属蛋白酶2和基质金属蛋白酶9的调控及其在主动脉瘤发生发展中的作用

主动脉瘤(AA)是一种发病率和死亡率都很高的心血管疾病,且发病机制极其复杂。研究证实microRNA(miRNA)可以调节AA的多种病理生理过程,包括炎症、细胞外基质(ECM)重构、血管平滑肌细胞增殖和死亡等。基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)是MMP蛋白酶家族中的重要成员,同样在AA的上述病理生理过程中起着重要作用。近年来发现多种miRNA可通过直接或间接的方式调节AA中MMP-2和MMP-9的表达和活性,从而影响AA的发生发展。文章主要总结了miRNA对MMP-2、MMP-9的调控机制及其在AA病变中的作用,旨在为AA的诊断和治疗提供新思路。     

L-arginine attenuates acute pulmonary embolism-induced increases in lung matrix metalloproteinase-2 and matrix metalloproteinase-9

STUDY OBJECTIVES: To evaluate the effects of L-arginine on acute pulmonary embolism (APE)-induced pulmonary hypertension and increases in lung matrix metalloproteinase (MMP)-2 and MMP-9 activities. DESIGN: Prospective trial. SETTING: University laboratory. INTERVENTIONS: Using an isolated lung perfusion rat model of APE, we examined whether L-arginine (0, 0.5, 3, and 10 mmol/L; five to seven rats per group) attenuates the pulmonary hypertension induced by the injection of 6.6 mg/kg of 300 microm microspheres into the pulmonary artery. In a second series of experiments (6 to 11 rats per group), we investigated whether nonselective inhibition of nitric oxide (NO) synthases with N(G)-nitro-L-arginine methyl ester (L-NAME; 4 mmol/L) decreases the effects produced by L-arginine. Lung MMP-2 and MMP-9 activities were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis gelatin zymography. RESULTS: L-arginine at 0.5, 3, and 10 mmol/L attenuated APE-induced pulmonary hypertension by 25 to 42% (all p < 0.05). The protective effect of L-arginine was completely reversed by inhibition of NO synthesis with L-NAME. APE was associated with increased lung MMP-2 and MMP-9 activities (both p < 0.05). While L-arginine at 0.5 mmol/L produced no effect on MMPs, L-arginine 3 at mmol/L and 10 mmol/L attenuated the increases in MMP-2 and MMP-9 activities after APE (both p < 0.05). CONCLUSIONS: L-arginine attenuates APE-induced pulmonary hypertension through mechanisms involving increased NO synthesis and maybe attenuation of lung MMP-2 and MMP-9 activities.     

Expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in recurrent chronic rhinosinusitis with nasal polyposis

Matrix metalloproteinase (MMP) is involved in the upper airway remodeling process. We hypothesized that MMP had an additive effect on the formation of recurrent nasal polyp. We also investigated the association between the functional promoter polymorphism of MMPs and the intensity of labeling index. Expressions of MMP-2 and MMP-9 were assessed via immunohistochemical staining and compared between different groups, including recurrent nasal polyps, nonrecurrent nasal polyps, and control nasal mucosa. Two promoter functional single-nucleotide polymorphisms (rs3918242 for MMP-9 and rs243865 for MMP-2) were selected to correlate with staining intensity. Expression of MMP-9 was significantly enhanced in gland for recurrent nasal polyp (p = 0.016) and nonrecurrent nasal polyp (p = 0.005) compared to the control. MMP-2 positivity was significantly increased in surface epithelium for recurrent nasal polyp (p = 0.004) compared to the control (p = 0.061). However, there was no significant difference in MMP-9 and MMP-2 expressions between recurrent and nonrecurrent nasal polyps. Genetic polymorphism of MMP-2 and MMP-9 functional promoters was not associated with the intensity of labeling index. These results suggested that up-regulation of MMP-9 in gland and MMP-2 in surface epithelium was characteristic of both recurrent and nonrecurrent nasal polyps. Pathogenesis of recurrent nasal polyps may involve a mechanism other than MMP.     

Increased activity of matrix metalloproteinase-8 and matrix metalloproteinase-9 in induced sputum from patients with COPD

BACKGROUND: The increased expression of matrix metalloproteinases (MMPs) is considered to be a key factor in the development of COPD. Net MMP activity represents a tightly regulated process, which is not addressed by conventional investigation methods such as messenger RNA or protein expression. Yet, quantitative data on MMP activity in the airways of COPD patients are lacking. METHODS: We used specific immunocapture assays to quantify the activity of MMP collagenase (ie, MMP-1, MMP-8, and MMP-13) and MMP gelatinase (ie, MMP-2 and MMP-9) in the induced sputum of COPD patients (17 patients; FEV(1), 56% predicted) and healthy smokers (17 subjects; FEV(1), 99% predicted). RESULTS: Levels of total and active MMP-8 and MMP-9 were significantly increased in COPD patients vs control subjects, whereas MMP-1 activity levels were similar in both groups. The activity of MMP-2 and MMP-13 remained below the detection threshold of the assays. MMP-8 and MMP-9 activity were strongly related to neutrophilia in both groups, and the results of immunohistochemistry tests on sputum cytospins showed that MMP-9 was expressed in both alveolar macrophages and neutrophils, whereas MMP-8 expression was exclusively observed in neutrophils. A positive correlation was found between sputum MMP-8 and MMP-9 activity and the degree of airflow limitation. CONCLUSION: We demonstrate increased MMP-8 and MMP-9 activity in the airway compartment of patients with mild-to-moderate COPD. This study provides further evidence of an impaired proteinase-antiproteinase balance in COPD patients.     

基质金属蛋白酶2、基质金属蛋白酶9与急性肺损伤关系的研究进展

急性肺损伤是由多种肺内外因素如严重创伤、感染、休克、脓毒症和大量输血等原因引起的弥漫性肺实质损伤.各种原因引起一系列炎症细胞在肺内聚集和活化,释放细胞因子、生长因子及其他炎症介质,引起基质金属蛋白酶(MMP)的合成和活化.MMP-2、MMP-9通过破坏基底膜、促进炎症过程中有关细胞的迁移以及细胞外基质重建,在急性肺损伤...