软骨寡聚基质蛋白对骨关节炎软骨破坏早期诊断价值的研究

目的 探讨软骨寡聚基质蛋白(COMP)对骨关节炎软骨破坏早期诊断价值.方法 兔右后膝伸直位石膏管型固定法制作骨关节炎模型;形态学方法观察造模不同时期关节病理切片;免疫组织化学方法检测软骨内COMP水平;酶联免疫吸附试验(ELISA)方法检测血清COMP水平.应用t检验,Pearson相关性分析.结果 ①伸直位石膏管型制动2周,模型关节呈现早期骨关节炎改变,制动6周呈现典型的中晚期骨关节炎特征;②造模前、模型2周、模型6周血清COMP含量分别是[(3.35±0.20)、(3.64±0.18)、(3.96±0.44)μg/L,P均＜0.05];③未造模、模型2周、模型6周关节软骨内COMP表达强度分别是[(2.7±1.8)%,(5.7±0.7)%,(7.6±0.7)%,P均＜0.05];④模型2周血清COMP水平与模型2周组、模型6周组OA病理评分存在线性相关关系(r均＞0.770,P均＜0.05).结论 骨关节炎血清COMP检测对早期诊断骨关节炎软骨破坏具有重要的意义.

Abstract：

Objective To study the diagnostic value of cartilage oligomeric matrix protein for early cartilage destruction in osteoarthritis and assess its value in the prediction of the disease progression.Methods The osteoarthritis animal models were developed by immobilizing the right knees of 18 rabbits in full extension position using plaster East.Knee joint pathological changes at week 2 and 6 were examined for pathological severity evaluation of osteoarthritis.ELISA sandwich method was used to measure the levels of cartilage oligomeric matrix protein(COMP) in serum before and after modeling(at week 2 and 6 respectively) and immunohistolgy method was used to examine the levels of COMP in knee articular cartilage of osteoarthritis animal models.Correlation analysis was performed to demonstrate the relationship between the levels of COMP in the serum and the pathological severity of osteoarthritis.Pearson's test and t-test were used for correlation analysis.Results ①) Osteoarthritis animal models could be successfully developed by immobilizing the right knees of rabbits in full extension position using plaster east for 2 weeks.Early histopathological changes in the articular cartilage could be observed,At week 6,the typical histopathological characteristics could be seen.②With the extension of modeling time,serum COMP levels persistently increased.The serum COMP levels before modeling,at modeling week 2,week 6 were (3.35±0.20),(3.64±0.18),(3.96±0.44) μg/L respectively,the difference was significant (P＜0.05).③ The level of COMP in the articular cartilage of non-osteoarthritis animal models,models at week 2,week 6 were (2.7±1.8 )％ ,(5.7±0.7)％,(7.6±0.7)％ respectively (P＜0.05 for all).④ The level of COMP in the serum was linearily correlated with the pathological severity of osteoarthritis(r＞0.770 for all,and P＜0.05 for all).Conclusion Levels of COMP in the serum can help to make early diagnosis of osteoarthritis,and elevated COMP level can predict the progression of osteoarthritis.     

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.     

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.     

Elevated serum levels of MMP-1 are related to atherosclerosis of the vessel proximal to the myocardial bridge

Background Atherosclerosis (AS) of the vessel proximal to the myocardial bridge (MB) is usually found in patients with chest pain undergoing coronary angiography. Matrix metalloprotease-1 (MMP-1) plays an essential role in the initiation and progression of AS. However, its role in AS of the vessel proximal to the MB is unclear. Objective The role of MMP-1 in AS of the vessel proximal to the MB was investigated [VAC1]. Methods We measured MMP-1 serum levels and compared clinical characteristics between two groups. Results MMP-1 serum levels were higher in Group 1 than in Group 2 (25.7 ± 6.1 ng / mL vs 12.6 ± 5.8 ng / mL, P < 0.001); Clinical characteristics had no significant difference between two groups. Conclusion Increased serum levels of MMP-1 might be associated with AS of the vessel proximal to the MB in the mid LAD.     

肌抑制素与慢性阻塞性肺疾病患者的营养不良

目的 调查慢性阻塞性肺疾病(COPD)稳定期患者的营养状况,通过检测外周血清中肌抑制素的水平,探讨肌抑制素与COPD患者营养不良的关系.方法 选71例COPD稳定期患者和60例老年健康对照者,参照营养不良多参数评分(MNI)对所有受试者的营养状况进行总体评价;采用酶联免疫吸附法检测受试者血清中肌抑制素、TNFα、C反应蛋白(CRP)水平.结果 COPD患者MNI显著升高,其中MNI≥5分者55例(77%),MNI＜5分者16例.MNI≥5分者血清中肌抑制素水平为(12.18±4.76)μg/L,较MNI＜5分者[(9.73±2.85)μg/L]和健康对照者[(7.93±2.35)μg/L]显著升高(P＜0.001).COPD患者TNFα显著升高,与健康对照者比差异有统计学意义(P＜0.05).COPD患者血清肌抑制素水平与MNI、TNFα水平呈正相关(r=0.438,P=0.000;r=0.234,P=0.041).结论 COPD患者普遍存在较严重的营养不良,血清肌抑制素水平明显升高,营养不良与血清肌抑制素升高密切相关.

Abstract：

Objective To investigate the prevalence and severity of malnutrition in patients with stable chronic obstructive pulmonary disease (COPD) , analyze serum levels of myostatin, tumor necrosis factor alpha (TNFα) and C reactive protein (CRP) , and investigate the relationship between serum myostatin and malnutrition in COPD. Methods Seventy-one patients with stable COPD and 60 age-matched healthy volunteers were recruited in this study. Pulmonary function was tested in all of the subjects and the severity of malnutrition was evaluated by a multiple-parameter malnutritional index (MNI). Based on the MNI scores, patients with COPD were divided into group Ⅰ (MNI≥5 score) and group Ⅱ (MNI ＜ 5 score) , the former represents the patients with severe or very severe malnutrition while the latter represents the patients with mild or without malnutrition. Serum concentration of myostatin, TNFα and CRP were measured by enzyme-linked immunosorbent assay. Results The MNI score was significantly elevated in patients with COPD [(7. 75 ±3. 86)score] compared with the controls [(1. 13 ±0. 96)score; P＜0.001],and 55 patients (77%) in COPD group Ⅰ showed MNI ≥ 5 (9. 30 ± 3. 01) score. Serum myostatin concentration was significantly elevated in COPD group Ⅰ [(12. 18 ±4. 76)μg/L] than in COPD group Ⅱ [(9. 73 ±2.85) μgL] and controls [(7.93 ±2.35) μg/L], with each P ＜ 0.001. Serum TNFα concentration was also significantly elevated in patients with COPD compared with the controls (P ＜ 0. 001).Pearson correlation analysis showed that serum myostatin levels were significantly correlated with MNI scores (r = 0. 438, P - 0. 000) and TNFa levels (r = 0. 234, P = 0. 041) in COPD group (combined group I and Ⅱ) while MNI scores were correlated inversely with BMI in COPD group (r = - 0. 530, P = 0. 000) . After stratified with subgroups, the correlation between myostatin levels and MNI scores was more significant and the correlation coefficient was higher (r =0.464, P =0.000) in COPD group I patients. Moreover,myostatin levels were inversely correlated with BMI (r = - 0. 287, P = 0. 034) and forced expiratory volume in one second of the predicted value (r = - 0. 264, P = 0. 049) in COPD group I patients. Conclusions Malnutrition commonly and substantially exists in patients with COPD; serum myostatin concentration is significantly elevated and is correlated with the severity of malnutrition in the patients. The elevation of serum myostatin may contribute to malnutrition in COPD patients.     

过敏性紫癜患儿血清胰岛素样生长因子及胰岛素样生长因子结合蛋白-3的变化

目的 探讨胰岛素样生长因子(IGF)-1及胰岛素样生长因子结合蛋白(IGFBP)-3在过敏性紫癜(HSP)中的作用.方法 采用放射免疫法方法测定45例HSP患儿不同时期的血清IGF-1及IGFBP-3、C反应蛋白(CRP)水平.采用t检验和直线相关关系.结果 HSP急性发作组血清IGF-1[(452±183)μg/L]、IGFBP-3[(13 897±3124)μg/L]及CRP[(20±8)mg/L]水平升高,与健康对照组和缓解组比较,差异均有统计学意义(t值分别为3.42、4.10、11.17、11.63、8.59、9.86.P均<0.01);HSP缓解组血清IGF-1、IGFBP-3及CRP与健康对照组比较,差异无统计学意义(t=0.3,4、0.34、0.52,P均>0.05).HSP急性期并发肾损害组血清IGF-1[(621±253)μg/L]、IGFBP-3[(18 763±3173)μg/L]水平升高,与无肾损害组比较,差异有统计学意义(t值分别为4.21、7.26,P均<0.01),有胃肠道症组血清IGF-1[(479±192)μg/L]、IGFBP-3[(13 986±3162)μg/L]水平与无胃肠道症状组比较,差异无统计学意义(t值分别为0.83、0.16,P均>0.05);血清CRP水平在肾损害组与非肾损害组及胃肠道症组与无胃肠道症状组问差异均无统计学意义(t值分别为0.56、0.32.P均>0.05).HSP急性期患儿血IGF-1、IGFBP-3与CRP浓度之间呈直线正相关(r值分别为0.624,0.672,JP均<0.01).结论 IGF-1、IGFBP-3参与了HSP疾病的病理生理过程,血清IGF-1、IGFBP-3测定对紫癜性肾损害的诊断、病情监测及预后判断有一定帮助.

Abstract：

Objecfive To investigate the role of serum Insulin-like growth factor(IGF)-1,insulinlike growth factor-binding potein(IGFBP)-3 in children with Henoch-Schonlein purpura(HSP).Methods The serum concentration of IGF-1,1GFBP-3 was measured by enzyme-linked immunosorbent assay(ELISA)method in 45 acute SHP patients,40 recoverv patients and 30 healthy controls.Results The serum levels of IGF-1 [(452±183)μg/L],IGFBP-3 [(13 897±3124)μg/L] and C-reactive protein(CRP)[(20±8)mg/L]in acute phase were significantly higher than those in healthy controls(P<0.0 1)and higher than those during recovery period.The serum level of IGF-1,IGFBP-3 for the HSP patients dropped back slowly and their levels during recovery period were the same as those in healthy controls(P>0.05).The serum levels of IGF-1[(621±253)μg/L] and IGFBP-3[(18 763±3173)μg/L] were higher in the renal damage group than in the non-renal damage group(P<0.01).and the same in patients with gastrointestinal symptoms group as in patients without gastrointestinal symptoms group(P>0.05).whereas the serum level of CRP was not significantly different(P>0.05).The serum levels of IGF-1,IGFBP-3 showed positive correlation with the level of CRP(r=0.624,0.672,P<0.01).Conclusion The IGF-1 and IGFBP-3 may play an important role in the pathological mechanism of HSP.The level of IGF-1 may be used as an indicator for HSP disease activity and progression.IGF-1 mav have a close relation with the damage"of renaJ system in HSP.     

Elevated Inflammation Markers are Negatively Associated With Plasma Free Testosterone Level in Male Patients With Acute Coronary Syndrome

Objectives To evaluate the levels of total testosterone （TT）, free testosterone （FT）, matrix metalloproteinase-9（MMP-9）,and tissue inhibitor of metalloproteinase-1（TIMP-1）, soluble intercellular adhesion molecule-1 （sICAM-1）, C-reactive protein （CRP）and association between them in male patients with different type of coronary heart diseases, and to assess the role they played in the pathogenesis of male acute coronary syndrome（ACS）.Methods 90 patients with coronary heart disease （CHD） including acute myocardial infarction （AMI）, unstable angina pectoris（UAP） , stable angina pectoris（SAP）and 30 healthy volunteers as controls were recruited. Serum concentrations of MMP-9, TIMP-1,sICAM-1 were measured with ELISA kits. CRP levels were measured with immunoturbidimetric assay, and white blood cell count （WBC） were also assessed before any treatment was administrated . Results ① The serum levels of free testosterone were significantly lower in patients with ACS （14.41±3.97 pg/mL in AMI group, 17.22±4.05 pg/mL in UAP group, and 26.49±8.72 pg/mL in control group）. MMP-9 levels （257.38±37.14 μg/L in AMI, 147.91±32.47 μg/L in UAP, and 57.26±31.75 μg/L in controls） and the ratios of MMP-9/TIMP-1 （4.23±0.51 in AMI, 2.32±0.38 in UAP, and 1.02±0.32 in controls）, meanwhile, were notably higher in ACS patients than those in control group（P〈 0.01）. ② Significant negative correlation between the serum levels of testosterone and MMP-9（-0.328 for TT, P〈0.05; -0.542 for FT,P 〈 0.01）, and MMP-9/TIMP-1（-0.309 for TT, P〈0.05; -0.519 for FT, P〈0.01） were observed in ACS groups. ③ The serum levels of sICAM-1, CRP and WBC in the patients with ACS were significantly higher than those in the control group （P〈 0.01）. Conclusions The elevation of serum concentrations of inflammatory markers including MMP-9, sICAM-1, CRP and WBC are associated with initiation and progression of ACS, while there are significant negative correlation between th     

肌抑制素与慢性阻塞性肺疾病患者的营养不良

Objective To investigate the prevalence and severity of malnutrition in patients with stable chronic obstructive pulmonary disease (COPD) , analyze serum levels of myostatin, tumor necrosis factor alpha (TNFα) and C reactive protein (CRP) , and investigate the relationship between serum myostatin and malnutrition in COPD. Methods Seventy-one patients with stable COPD and 60 age-matched healthy volunteers were recruited in this study. Pulmonary function was tested in all of the subjects and the severity of malnutrition was evaluated by a multiple-parameter malnutritional index (MNI). Based on the MNI scores, patients with COPD were divided into group Ⅰ (MNI≥5 score) and group Ⅱ (MNI ＜ 5 score) , the former represents the patients with severe or very severe malnutrition while the latter represents the patients with mild or without malnutrition. Serum concentration of myostatin, TNFα and CRP were measured by enzyme-linked immunosorbent assay. Results The MNI score was significantly elevated in patients with COPD [(7. 75 ±3. 86)score] compared with the controls [(1. 13 ±0. 96)score; P＜0.001],and 55 patients (77%) in COPD group Ⅰ showed MNI ≥ 5 (9. 30 ± 3. 01) score. Serum myostatin concentration was significantly elevated in COPD group Ⅰ [(12. 18 ±4. 76)μg/L] than in COPD group Ⅱ [(9. 73 ±2.85) μgL] and controls [(7.93 ±2.35) μg/L], with each P ＜ 0.001. Serum TNFα concentration was also significantly elevated in patients with COPD compared with the controls (P ＜ 0. 001).Pearson correlation analysis showed that serum myostatin levels were significantly correlated with MNI scores (r = 0. 438, P - 0. 000) and TNFa levels (r = 0. 234, P = 0. 041) in COPD group (combined group I and Ⅱ) while MNI scores were correlated inversely with BMI in COPD group (r = - 0. 530, P = 0. 000) . After stratified with subgroups, the correlation between myostatin levels and MNI scores was more significant and the correlation coefficient was higher (r =0.464, P =0.000) in COPD group I patients. Moreover,myostatin levels were inversely correlated with BMI (r = - 0. 287, P = 0. 034) and forced expiratory volume in one second of the predicted value (r = - 0. 264, P = 0. 049) in COPD group I patients. Conclusions Malnutrition commonly and substantially exists in patients with COPD; serum myostatin concentration is significantly elevated and is correlated with the severity of malnutrition in the patients. The elevation of serum myostatin may contribute to malnutrition in COPD patients.     

肌抑制素与慢性阻塞性肺疾病患者的营养不良

Objective To investigate the prevalence and severity of malnutrition in patients with stable chronic obstructive pulmonary disease (COPD) , analyze serum levels of myostatin, tumor necrosis factor alpha (TNFα) and C reactive protein (CRP) , and investigate the relationship between serum myostatin and malnutrition in COPD. Methods Seventy-one patients with stable COPD and 60 age-matched healthy volunteers were recruited in this study. Pulmonary function was tested in all of the subjects and the severity of malnutrition was evaluated by a multiple-parameter malnutritional index (MNI). Based on the MNI scores, patients with COPD were divided into group Ⅰ (MNI≥5 score) and group Ⅱ (MNI ＜ 5 score) , the former represents the patients with severe or very severe malnutrition while the latter represents the patients with mild or without malnutrition. Serum concentration of myostatin, TNFα and CRP were measured by enzyme-linked immunosorbent assay. Results The MNI score was significantly elevated in patients with COPD [(7. 75 ±3. 86)score] compared with the controls [(1. 13 ±0. 96)score; P＜0.001],and 55 patients (77%) in COPD group Ⅰ showed MNI ≥ 5 (9. 30 ± 3. 01) score. Serum myostatin concentration was significantly elevated in COPD group Ⅰ [(12. 18 ±4. 76)μg/L] than in COPD group Ⅱ [(9. 73 ±2.85) μgL] and controls [(7.93 ±2.35) μg/L], with each P ＜ 0.001. Serum TNFα concentration was also significantly elevated in patients with COPD compared with the controls (P ＜ 0. 001).Pearson correlation analysis showed that serum myostatin levels were significantly correlated with MNI scores (r = 0. 438, P - 0. 000) and TNFa levels (r = 0. 234, P = 0. 041) in COPD group (combined group I and Ⅱ) while MNI scores were correlated inversely with BMI in COPD group (r = - 0. 530, P = 0. 000) . After stratified with subgroups, the correlation between myostatin levels and MNI scores was more significant and the correlation coefficient was higher (r =0.464, P =0.000) in COPD group I patients. Moreover,myostatin levels were inversely correlated with BMI (r = - 0. 287, P = 0. 034) and forced expiratory volume in one second of the predicted value (r = - 0. 264, P = 0. 049) in COPD group I patients. Conclusions Malnutrition commonly and substantially exists in patients with COPD; serum myostatin concentration is significantly elevated and is correlated with the severity of malnutrition in the patients. The elevation of serum myostatin may contribute to malnutrition in COPD patients.     

肌抑制素与慢性阻塞性肺疾病患者的营养不良

Objective To investigate the prevalence and severity of malnutrition in patients with stable chronic obstructive pulmonary disease (COPD) , analyze serum levels of myostatin, tumor necrosis factor alpha (TNFα) and C reactive protein (CRP) , and investigate the relationship between serum myostatin and malnutrition in COPD. Methods Seventy-one patients with stable COPD and 60 age-matched healthy volunteers were recruited in this study. Pulmonary function was tested in all of the subjects and the severity of malnutrition was evaluated by a multiple-parameter malnutritional index (MNI). Based on the MNI scores, patients with COPD were divided into group Ⅰ (MNI≥5 score) and group Ⅱ (MNI ＜ 5 score) , the former represents the patients with severe or very severe malnutrition while the latter represents the patients with mild or without malnutrition. Serum concentration of myostatin, TNFα and CRP were measured by enzyme-linked immunosorbent assay. Results The MNI score was significantly elevated in patients with COPD [(7. 75 ±3. 86)score] compared with the controls [(1. 13 ±0. 96)score; P＜0.001],and 55 patients (77%) in COPD group Ⅰ showed MNI ≥ 5 (9. 30 ± 3. 01) score. Serum myostatin concentration was significantly elevated in COPD group Ⅰ [(12. 18 ±4. 76)μg/L] than in COPD group Ⅱ [(9. 73 ±2.85) μgL] and controls [(7.93 ±2.35) μg/L], with each P ＜ 0.001. Serum TNFα concentration was also significantly elevated in patients with COPD compared with the controls (P ＜ 0. 001).Pearson correlation analysis showed that serum myostatin levels were significantly correlated with MNI scores (r = 0. 438, P - 0. 000) and TNFa levels (r = 0. 234, P = 0. 041) in COPD group (combined group I and Ⅱ) while MNI scores were correlated inversely with BMI in COPD group (r = - 0. 530, P = 0. 000) . After stratified with subgroups, the correlation between myostatin levels and MNI scores was more significant and the correlation coefficient was higher (r =0.464, P =0.000) in COPD group I patients. Moreover,myostatin levels were inversely correlated with BMI (r = - 0. 287, P = 0. 034) and forced expiratory volume in one second of the predicted value (r = - 0. 264, P = 0. 049) in COPD group I patients. Conclusions Malnutrition commonly and substantially exists in patients with COPD; serum myostatin concentration is significantly elevated and is correlated with the severity of malnutrition in the patients. The elevation of serum myostatin may contribute to malnutrition in COPD patients.     

C57黑鼠骨关节炎模型的关节病理积分与血清及滑膜中基质金属蛋白酶-3白细胞介素-1水平的相关性研究

目的 探讨基质金属蛋白酶(MMP)-3与白细胞介素(IL)-1在骨关节炎(OA)发病中所起的作用及其用于临床判断OA早期病理变化的可能性.方法 采用C57黑鼠OA模型.在自然增龄基础上,又对小鼠进行运动负荷训练.应用形态学方法对模型关节的病理切片观察,进行OA积分评分.研究采用酶联免疫吸附试验(ELISA)的方法.检测血清及滑膜中MMP-3、IL-1的水平.采用相关性分析来检验血清和滑膜中MMP-3、IL-1水平之间的关系,以及与OA积分评分之间的相关性.结果 ①形态学观察:C57黑鼠具有自发OA特征,其OA严重程度与周龄相关,且运动负荷可加快有自发OA倾向的小鼠关节软骨病理改变.②ELISA检测:运动负荷组滑膜中MMP-3[(84±6)ng/ml]、IL-1[(48±3)ng/ml]及血清中IL-1[(38.3±5.0 mg/ml]含量高于自然增龄组[滑膜MMP-3(71±5)ng,ml;IL-1(42±3)ng/ml;血清IL-1(8.1±2.4)ng/ml],差异有统计学意义(P<0.01);血清与滑膜中MMP-3、IL-1水平、OA评分存在线性相关[r均>0.67,P均<0.01].结论 联合检测MMP-3及IL-1在OA血清中的含量,有助于疾病的诊断与病情的判断.特别是MMP-3对于OA的早期诊断具有更为重要的意义.     

Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: the Johnston County Osteoarthritis Project.

OBJECTIVE: To characterize serum cartilage oligomeric matrix protein (COMP) levels by age and gender for a radiographically defined population free of hip and knee osteoarthritis (OA), and to examine the potential utility of COMP as a diagnostic biomarker for knee OA. METHODS: Serum samples and knee and hip radiographs were obtained at a baseline evaluation as part of the Johnston County Osteoarthritis Project, a population-based study of OA in rural North Carolina. A total of 291 Caucasian participants were randomly selected for COMP analysis, 143 patients with radiographic knee OA (Kellgren/Lawrence [K/L] grade > or = 2) and 148 controls with neither hip nor knee OA (K/L grade 0), evenly distributed by age and gender. COMP was quantified by competitive enzyme-linked immunosorbent assay with monoclonal antibody 17-C10. The natural log-transformed COMP data were analyzed using general linear models. RESULTS: Serum COMP levels were significantly elevated (P = 0.0001) in the age > or = 65 group (mean +/- SD 1,302.1 +/- 496.7 ng/ml) versus the age 45-54 and age 55-64 groups (1,058.1 +/- 432.4 and 1,038.6 +/- 313.3, respectively). Serum COMP levels of the OA group were significantly higher than those of the control group (1,208.57 +/- 487.47 ng/ml versus 1,061.83 +/- 370.58 ng/ml; P = 0.0093). Serum COMP levels also increased significantly with knee OA K/L grade (P = 0.0047), knee OA laterality (P = 0.0043), and number of knee and hip joints involved (P = 0.0001). There was no significant difference in serum COMP levels by gender or obesity. CONCLUSION: We demonstrate that in a population-based sample, serum COMP levels can distinguish an OA-affected subgroup from an unaffected subgroup and can reflect disease severity and multiple joint involvement in OA.     

Luminex液相蛋白芯片检测一氧化氮合酶抑制剂对骨关节炎患者软骨基质金属蛋白酶表达的影响

目的 应用Luminex液相蛋白芯片检测一氧化氮合酶(NOS)抑制剂对骨关节炎(OA)患者软骨基质金属蛋白酶(MMPs)表达的影响,以及NOS抑制剂改善OA代谢的途径.方法 研究经本院医学伦理委员会批准并获取患者的知情同意.无菌条件下,取15例重度OA需行关节置换术患者的关节软骨,置入体外培养系统.应用随机数目表法分为:①对照组:不加药物干预;②L-N6-亚氨乙基-赖氨酸(L-NIL)组:加入NOS抑制剂L-NIL干预.培养72 h后,通过检测硝酸盐和亚硝酸盐的含量来观察软骨一氧化氮(NO)的释放量和NOS的活性;应用Luminex液相蛋白芯片检测OA患者软骨中MMPs(MMP-1,MMP-2,MMP-3,MMP-9,MMP-13)表达量的变化.数据采用配对t检验作均数的显著性检验.结果 对照组软骨培养72 h后,在其上清液中可检测到高浓度NO[(216±47)μmol/L]和高活性的NOS[(5.7±1.3)U/ml],L-NIL组NO释放量[(55±20)μmol/L]较对照组明显减少,NOS活性[(1.7±0.7)U/m1]显著降低(P均<0.01).Luminex液相蛋白芯片显示对照组OA软骨中MMPs[(MMP-1 (10.8±5.4)ng/ml,MMP-2 (9.2±3.3)ng/ml,MMP-3(11.6±4.2)ng/ml,MMP-9(1.27±1.07)ng/ml,MMP-13(3.6±1.3)ng/ml)的表达异常,而L-NIL组OA软骨中MMPs表达量明显被抑制[分别为(3.6±1.8)ng/ml,(2.3±1.2)ng/ml,(3.6±1.4)ng/ml,(0.65±0.21)ng/ml,(1.8±0.5)ng/ml,P均<0.05].结论 Luminex液相蛋白芯片检测系统表明NOS 抑制剂通过减少NO的过度释放和降低NOS活性,进而抑制MMPs的过度表达来改善OA软骨的代谢.     

戒烟对大鼠血清瘦素、脂联素等炎症因子的影响

目的 通过研究戒烟对大鼠血清瘦素、脂联素、白介素6(IL-6)及C反应蛋白(CRP)水平的影响,探讨瘦素和脂联素等炎症因子在吸烟所致慢性阻塞性肺疾病炎症反应中的作用.方法 雄性Wistar大鼠30只,随机分为吸烟组、戒烟组及对照组,每组各10只.吸烟组每次吸烟10支,每天吸烟2次,每周吸烟6 d,共吸烟20周;戒烟组为吸烟20周后戒烟10周.采用酶联免疫吸附法检测各组大鼠血清瘦素、脂联素及CRP水平,采用双抗体夹心酶联免疫吸附法检测各组大鼠血清IL-6水平.结果 ①与对照组[(128.00±13.25) ng/L]比较,吸烟组[(56.23±8.64)ng/L]及戒烟组[(60.36±7.42)ng/L]血清瘦素水平均降低(P值均<0.05);戒烟组与吸烟组比较差异无统计学意义.②与对照组L(0.369±0.032)μg/L]比较,吸烟组[0.322±0.045)μg/L]血清脂联素水平降低(P<0.05),而戒烟组L(0.333±0.059)μg/L]与对照组、吸烟组比较差异无统计学意义.③与对照组[(23.94±4.44)ng/L]比较,吸烟组[(39.67±3.13)ng/L]及戒烟组[(34.27±7.01)ng/L]血清IL-6水平均升高(P值均<0.05);戒烟组较吸烟组水平降低(P<0.05).④与对照组[(494.49±124.44)μg/L]比较,吸烟组[(809.50±141.66)μg/L]及戒烟组[(632.60±182.85)μg/L]血清CRP水平均升高(P值均<0.05);戒烟组较吸烟组水平降低(P<0.05).⑤脂联素水平分别与IL-6和CRP呈负相关(γ值分别为-0.198、-0.489,P值均<0.05);IL-6水平与CRP呈止相关(γ=0.598,P<0.05).结论吸烟可使大鼠血清瘦素与脂联素水平下降,IL-6与CRP水平升高;戒烟后,瘦素、脂联素水平呈上升趋势,IL-6和CRP水平则相应下降.此外,脂联素水平分别与IL-6和CRP呈负相关.提示瘦素、脂联素等炎症因子可能参与吸烟所致慢性阻塞性肺疾病的炎症反应.     

血清淀粉样蛋白A在类风湿关节炎患者体内表达的研究

目的 通过检测血清淀粉样蛋白A(SAA)在类风湿关节炎(RA)患者血清、关节液及滑膜中的表达,探讨其在RA发病机制中的作用.方法 采用酶联免疫吸附试验(ELISA)分别检测RA、骨关节炎患者和健康对照人群血清以及RA与骨关节炎患者关节液中SAA的水平;蛋白印迹法测定SAA在血清中的表达;免疫组织化学技术检测RA和骨关节炎滑膜中SAA的表达.应用t检验或Kruska-Wallis秩和检验进行统计分析.结果 RA血清中SAA含量[(318±132) μg/L]显著高于骨关节炎[(127±47) μg/L]和健康对照组[(127±41) μg/L,P均＜0.01].RA关节液中SAA含量[(571±473) μg/L]显著高于骨关节炎[(129±33) μg/L,t=2.46,P=0.04].蛋白印迹法结果显示各组血清样品中均有SAA条带;RA的SAA表达明显高于其他2组.病理结果显示SAA在RA关节滑膜高表达,位于血管内皮细胞、滑膜成纤维细胞、巨噬细胞以及血管周围;在骨关节炎,SAA仅见于关节血管周围和成纤维细胞.结论 RA血清和关节液中SAA的含量显著增高;SAA在RA滑膜组织中高表达,且表达位置与骨关节炎有明显差别,提示SAA可能参与了RA的炎症反应和关节损害.     

不稳定性心绞痛患者基质金属蛋白酶-1与细胞分化抗原40配体的研究

目的探讨自细胞分化抗原40配体（CD40L）介导基质金属蛋白酶-1（MMP-1）的表达与分泌在不稳定性心绞痛（UA）发病机制中所起的作用，以及MMP-1在UA患者危险度分层及预后价值中的作用。方法选择UA患者组64例，并按Braunwald分级分为Ⅰ、Ⅱ、Ⅲ级，选择稳定性心绞痛（SA）患者组56例及健康对照组40例，采用酶联免疫吸附法分别测定各组血清可溶性CD40L（sCD40L）、MMP-1的水平，分析UA组MMP-1与sCD40L之间的相关性，同时分析MMP-1水平与心血管事件发生率的相关性。结果（1）UA患者组MMP-1水平（53．53±18．25）μg／L显著高于SA患者组（31．28±13．64）μg／L（P〈0.01）及对照组（11．58±9．83）μg／L（P〈0．05）；sCD40L水平（3．21±2．78）μg／L显著高于sA患者组（1．83±1．37）μg／L（P〈0.01）及对照组（1．19±1．05）μg／L（P〈0．01）。（2）UA患者组MMP-1与sCD40L水平之间呈显著正相关（r=0．642，P〈0．01）。（3）UA患者组MMP-1水平升高组发生心血管事件明显高于MMP-1水平低者组（P〈0．01）。结论（1）UA患者外周血sCD40L、MMP-1水平升高，MMP-1与CD40L之间呈显著正相关，提示冠状动脉粥样硬化斑块的破裂可能与CD40L介导MMP-1的表达与分泌有关。（2）UA患者MMP-1水平与心血管事件发生率之间呈正相关性，提示MMP-1可作为UA患者危险度分层及预后有价值的生化指标。     

应用N-乙酰半胱氨酸治疗慢性乙型肝炎重度患者临床疗效初步研究

目的 探讨应用注射用 N-乙酰半胱氨酸(NAC)治疗慢性乙型肝炎重度患者的临床疗效。方法 2015年1月～2018年12月我院诊治的慢性乙型肝炎重度患者62例,被分为观察组32例和对照组30例。在对照组,给予护肝、降黄、抗病毒等综合治疗,观察组在对照组治疗的基础上加用NAC静脉滴注,连续治疗6 w。采用放射免疫法检测血清Ⅲ型前胶原(PC-Ⅲ)、IV型胶原(IV-C)、血清透明质酸(HA)和层黏连蛋白(LN)]水平,采用ELISA法检测血清白介素-1β(IL-1β)、IL-6、IL-8和肿瘤坏死因子-α(TNF-α)水平。结果 在治疗6 w末,观察组血清ALT和AST水平分别为(45.4±2.9)U/L和(74.3±8.7)U/L,与对照组比较无显著性差异,观察组血清TBIL水平为(85.1±54.6)μmol/L,显著低于对照组;观察组血清PC-Ⅲ、IV-C、HA和LN水平分别为(87.1±15.8)μg/L、(74.5±15.2)μg/L 、(95.7±13.7)μg/L和(83.9±16.5)μg/L,显著低于对照组;观察组血清IL-6、IL-8和TNF-α水平分别为(15.1±2.8)μg/L、(5.2±2.9)μg/L和(13.7±0.9) μg/L,显著低于对照组;观察组病情控制率为87.1%,显著高于对照组。结论 应用NAC治疗慢性乙型肝炎重度患者临床疗效显著且无明显的不良反应,能降低血清胆红素和肝纤维化指标水平,减轻炎症相关的细胞因子水平。     

Serum cartilage oligomeric matrix protein (COMP) levels in knee osteoarthritis in a Brazilian population: clinical and radiological correlation

OBJECTIVES: In this study we present data on serum cartilage oligomeric matrix protein (COMP) levels in a Brazilian population with isolated knee osteoarthritis (OA) compared to healthy controls. Clinical and radiological correlations with COMP levels were also evaluated. METHODS: Two hundred and seventy-two patients seen at the Rheumatology Division of the Federal University of S?o Paulo (UNIFESP) with a symptom of 'pain in the knees' for at least 3 months were invited to participate in this study. History and clinical examination were performed in all patients. Eighty-six patients with clinical isolated knee OA according to the American College of Rheumatology (ACR) criteria and without other causes of pain in the knee were included. Fifty-eight healthy individuals were selected, matched for age and sex, and used as controls. OA evaluation included Lequesne and Western Ontario and MacMaster Universities osteoarthritis index (WOMAC) questionnaires, visual analogue scale (VAS) for pain and standard knee X-rays. Blood samples were taken from all participants and serum COMP levels were measured by enzyme-linked immunosorbent assay (ELISA). OA radiological analysis was performed using the Kellgren and Lawrence (K/L) grading scale. RESULTS: Patients with symptomatic knee OA presented significantly higher serum COMP levels compared to healthy controls and to those with non-symptomatic narrowing of the articular space (p<0.001). Patients with clinical evidence of knee OA and without radiological abnormalities (K/L grade 0 or 1) had intermediate serum COMP levels, significantly higher than those observed in healthy controls (p<0.03). CONCLUSIONS: We observed increased serum COMP levels in patients with symptomatic radiological knee OA. High serum COMP levels may also indicate cartilage damage in selected symptomatic patients without significant radiological abnormalities.