Matrix metalloproteinases, tissue inhibitors of metalloproteinases, aminoterminal propeptide of procollagen type III, and hyaluronan in sera and tissue of patients with capsular contracture after augmentation with Trilucent breast implants

In various fibrotic diseases, matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), play an important role. In our study, serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined by enzyme-linked immunosorbent assay in 17 female patients with Baker grade II (n =9), III (n =7), and IV (n =1) capsular contracture after bilateral cosmetic mamma augmentation with Trilucent implants (AEI, Inc., Caversham, United Kingdom). Samples of capsular tissue for standard histology and immunohistochemistry were obtained from all patients. Sera from 20 female patients who had plastic surgery for reduction mammaplasty were used as the control group. The aminoterminal propeptide of procollagen type III (PIIINP) and hyaluronan were analyzed as markers for fibrogenesis in both groups, too. Statistical analysis was performed using the Mann-Whitney test and Spearman rank correlation. Patients with capsular contracture presented significantly higher concentrations of TIMP-1 and TIMP-2 in their sera than did the control group (p < 0.05), which correlated with Baker grade (r = 0.7 versus r = 0.65; p < 0.05). The concentration of MMP-2 was significantly higher in the sera of patients with capsule fibrosis, whereas there were no significant differences in MMP-1, MMP-9, and PIIINP serum concentrations. Patients with capsule fibrosis had a significantly lower MMP-to-TIMP ratio (1.1 +/- 0.4, p <0.05) than the control group (1.5 +/- 0.4), which correlated with the Baker classification (r =0.7; p <0.05). The hyaluronan serum concentration of patients with capsular contracture was significantly higher (p < 0.05) and correlated with the Baker grade (r = 0.73; p < 0.05), whereas PIIINP showed no difference. In the histologic evaluation, there was a chronic inflammatory reaction in the capsules around the breast implants and refracting material within the substance. Immunohistochemically, TIMP-1 and TIMP-2 showed an intensive accumulation, and MMP-2 showed a local reaction. PIIINP could be detected, too, whereas there was no staining for MMP-1 and MMP-9.The elevated systemic MMP-2 concentration and the local positive staining in the tissue might be due to the chronic inflammatory reaction. Nevertheless, the balance between MMPs and their natural inhibitors is disturbed in patients with capsule contracture. The elevated systemic concentration of TIMPs might be a pathway in the pathogenesis of severe fibrosis after breast augmentation with alloplastic material. Hyaluronan might be a useful marker for early prediction of capsule fibrosis, whereas PIIINP is not useful as a predictor.     

黄葵胶囊联合阿魏酸哌嗪片对慢性肾小球肾炎患者肾功能、氧化应激和血清MMP-9、TIMP-1的影响

摘要 目的：观察黄葵胶囊联合阿魏酸哌嗪片治疗慢性肾小球肾炎患者的应用价值。方法：选择2019年4月~2021年1月期间我院收治的慢性肾小球肾炎患者131例,以双色球随机分组法将患者分为对照组65例（阿魏酸哌嗪片治疗）、实验组66例（黄葵胶囊联合阿魏酸哌嗪片治疗）。对比两组疗效、肾功能[血肌酐（Scr）、尿素氮（BUN）、24 h 尿蛋白定量（24 h-Upr）]、氧化应激[超氧化物歧化酶（SOD）、丙二醛（MDA）]和血清基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶组织抑制因子-1（TIMP-1）水平,记录两组不良反应发生率。结果：与对照组比较,实验组的临床总有效率明显更高（P<0.05）。与对照组相比,实验组治疗3个月后Scr、BUN、24 h-Upr更低（P<0.05）。与对照组相比,实验组治疗3个月后TIMP-1更低,MMP-9更高（P<0.05）。与对照组相比,实验组治疗3个月后MDA更低,SOD更高（P<0.05）。两组不良反应发生率组间对比无差异（P>0.05）。结论：黄葵胶囊联合阿魏酸哌嗪片治疗慢性肾小球肾炎,可减轻机体氧化应激,调节血清MMP-9、TIMP-1水平,促进肾功能改善,安全可靠。     

不同类型缺血性脑血管病血清VCAM-1、MMP-2、TIMP-1的表达及与神经功能缺损的关系分析

摘要 目的：探讨不同类型缺血性脑血管病血清血管细胞粘附分子-1（VCAM-1）、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶抑制剂1（TIMP-1）的表达及与神经功能缺损的关系。方法：选择2016年1月至2020年1月我院接诊的98例缺血性脑血管病患者为本研究对象,其中脑梗死55例设为脑梗死组,短暂性脑缺血发作组43例,并选择我院同期体检中心健康者50作为对照组,分析三组血清VCAM-1、MMP-2、TIMP-1水平之间的差异及不同神经缺损程度血清VCAM-1、MMP-2、TIMP-1水平、美国国立卫生研究院卒中量表（NIHSS）评分变化情况,及其之间的相关性。结果：脑梗死组血清VCAM-1、MMP-2、TIMP-1水平及NIHSS评分显著高于短暂性脑缺血发作组和对照组,差异显著（P＜0.05）;短暂性脑缺血发作组血清VCAM-1、MMP-2、TIMP-1水平及NIHSS评分显著高于对照组,差异显著（P＜0.05）;重度神经缺损组血清VCAM-1、MMP-2、TIMP-1水平及NIHSS评分显著高于中度神经缺损组和轻度神经缺损组,差异显著（P＜0.05）;中度神经缺损组血清VCAM-1、MMP-2、TIMP-1水平及NIHSS评分显著高于轻度神经缺损组,差异显著（P＜0.05）;相关性分析结果中显示,血清VCAM-1、MMP-2、TIMP-1均和NIHSS评分呈正相关（r=0.603, 0.915, 0.778,P＜0.05）。结论：血清VCAM-1、MMP-2、TIMP-1在缺血性脑血管病患者中表达异常,神经缺损越严重血清VCAM-1、MMP-2、TIMP-1表达越高。     

五灵胶囊联合富马酸丙酚替诺福韦片对慢性乙型肝炎患者氧化应激、CD4+CD25+调节性T细胞和血清MMP-1、MMP-2、TIMP-1的影响

摘要 目的：探讨五灵胶囊联合富马酸丙酚替诺福韦片对慢性乙型肝炎（CHB）患者氧化应激、CD4⁺CD25⁺调节性T细胞和血清基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶组织抑制因子-1（TIMP-1）的影响。方法：纳入苏州大学附属传染病医院2021年6月~2022年12月期间收治的CHB患者122例,采用随机数字表法分为对照组（n=61,富马酸丙酚替诺福韦片）和研究组（n=61,五灵胶囊联合富马酸丙酚替诺福韦片）。对比两组疗效、氧化应激指标、CD4⁺CD25⁺调节性T细胞、肝功能指标[总胆红素（TBIL）、谷丙转氨酶（ALT）、谷氨酰转肽酶（GGT）]、血清MMP-1、MMP-2、TIMP-1水平和不良反应发生情况。结果：研究组的临床总有效率高于对照组（P<0.05）。两组治疗后丙二醛（MDA）下降,且研究组低于对照组同时间点;超氧化物歧化酶（SOD）升高,且研究组高于对照组同时间点（P<0.05）。两组治疗后CD4⁺CD25⁺调节性T细胞下降,且研究组低于对照组同时间点（P<0.05）。两组治疗后MMP-1、MMP-2、TIMP-1下降,且研究组低于对照组同时间点（P<0.05）。两组治疗后TBIL、ALT、GGT下降,且研究组低于对照组同时间点（P<0.05）。两组不良反应总发生率组间对比未见差异（P>0.05）。结论：五灵胶囊联合富马酸丙酚替诺福韦片治疗CHB患者,可有效减轻机体氧化应激,调节CD4⁺CD25⁺调节性T细胞和血清MMP-1、MMP-2、TIMP-1水平。     

塞米松棕榈酸酯、维生素B12、利多卡因关节腔内注射对膝关节骨性关节炎患者血清IL-1，MMP-3及TIMP-1水平的影响

目的:研究塞米松棕榈酸酯、维生素B12、利多卡因联合使用对膝骨性关节炎的疗效及对血清白介素-1(IL-1)、软骨基质金属蛋白酶3(MMP-3)、基质金属蛋白酶抑制剂1(TIMP-1)的影响。方法:选取2014年8月至2015年7月新疆医科大学第六附属医院收治的84例膝骨性关节炎患者,根据入院顺序分为观察组和对照组,42例每组。观察组采取塞米松棕榈酸酯、维生素B12、利多卡因进行关节腔内注射,对照组采取中药涂抹方案。评判患者治疗后的临床疗效,比较两组患者治疗前和治疗1个月后血清IL-1、MMP-3、TIMP-1水平、视觉模拟(VAS)评分的变化。结果:治疗后,观察组临床总有效率显著高于对照组(P0.05),两组患者的血清IL-1、MMP-3、VAS评分均显著低于治疗前(P0.05),血清TIMP-1水平明显高于治疗前,且观察组的IL-1、MMP-3、TIMP-1、VAS评分水平显著低于对照组,血清TIMP-1水平明显高于对照组(P0.05)。结论:采取塞米松棕榈酸酯、维生素B12、利多卡因关节腔内注射治疗膝骨性关节炎患者能有效降低患者血清IL-1、MMP-3水平,升高TIMP-1水平,缓解患者疼痛感,临床疗效良好。     

肺癌患者血清中VEGF,TIMP-1和MMP-9水平变化及临床意义

目的:研究肺癌患者血清中血管内皮生长因子(VEGF)、组织金属蛋白酶抑制剂1(TIMP-1)、基质金属蛋白酶9(MMP-9)水平变化及临床意义。方法:选取2014年3月至2016年3月来我院治疗的91例肺癌患者为病例组,同期选取40例健康者为对照组,酶联免疫吸附测定法(ELISA)测定两组血清VEGF、TIMP-1、MMP-9水平,分析肺癌患者上述指标与病理特征的关系,并采用spearman检验分析相关性。结果:病例组血清VEGF、TIMP-1、MMP-9水平均高于对照组,差异均具有统计学意义(P0.05)。肺癌患者血清VEGF、TIMP-1、MMP-9水平均与肿瘤体积大小、TNM分期、淋巴结转移、远处转移有关(P0.05)。肺癌患者血清MMP-9与TIMP-1正相关(r=0.337,P0.05)、血清MMP-9与VEGF正相关(r=0.312,P0.05)、血清TIMP-1与VEGF正相关(r=0.316,P0.05)。结论:血清VEGF、TIMP-1、MMP-9相互作用、协同参与肺癌的发生及侵袭转移,可作为肺癌诊断及预后评估的生物学标志物。     

Matrix Metalloproteinases -8 and -9 and Tissue Inhibitor of Metalloproteinase-1 in Burn Patients. A Prospective Observational Study

IntroductionMatrix metalloproteinases (MMPs) -8 and -9 are released from neutrophils in acute inflammation and may contribute to permeability changes in burn injury. In retrospective studies on sepsis, levels of MMP-8, MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) differed from those of healthy controls, and TIMP-1 showed an association with outcome. Our objective was to investigate the relationship between these proteins and disease severity and outcome in burn patients.MethodsIn this prospective, observational, two-center study, we collected plasma samples from admission to day 21 post-burn, and burn blister fluid samples on admission. We compared MMP-8, -9, and TIMP-1 levels between TBSA<20% (N = 19) and TBSA>20% (N = 30) injured patients and healthy controls, and between 90-day survivors and non-survivors. MMP-8, -9, and TIMP-1 levels at 24-48 hours from injury, their maximal levels, and their time-adjusted means were compared between groups. Correlations with clinical parameters and the extent of burn were analyzed. MMP-8, -9, and TIMP-1 levels in burn blister fluids were also studied.ResultsPlasma MMP-8 and -9 were higher in patients than in healthy controls (P<0.001 and P = 0.016), but only MMP-8 differed between the TBSA<20% and TBSA>20% groups. MMP-8 and -9 were not associated with clinical severity or outcome measures. TIMP-1 differed significantly between patients and controls (P<0.001) and between TBSA<20% and TBSA>20% groups (P<0.002). TIMP-1 was associated with 90-day mortality and correlated with the extent of injury and clinical measures of disease severity. TIMP-1 may serve as a new biomarker in outcome prognostication of burn patients.     

Distribution of matrix metalloproteinases MMP-1, MMP-2, MMP-8 and tissue inhibitor of matrix metalloproteinases-2 in nasal polyposis and chronic rhinosinusitis

Nasal polyposis (NP), a chronic inflammatory disease of the upper airway, is a subgroup of chronic rhinosinusitis (CRS). Matrix metallo-proteinases (MMPs) and their tissue inhibitors (TIMPs) are considered to play important roles in the pathogenesis of nasal polyposis. The aim of the current study was to evaluate and compare the levels of MMP-1, MMP-2, MMP-8 and TIMP-2 in NP and CRS with normal nasal mucosa by using immunohistochemistry. Twenty-five patients with NP and fifteen patients with CRS underwent endoscopic sinus surgery. Diseased mucosal samples were obtained from ethmoidal sinuses. Control nasal mucosa (n=10) was obtained from inferior nasal turbinate. Immunohistochemistry for MMP-1, MMP-2, MMP-8 and TIMP-2 was performed. The expression of MMP-1, MMP-2 and MMP-8 significantly increased in NP and CRS compared with control (p<0.05). The distribution of TIMP-2 was higher in CRS than control and NP respectively (p<0.05). MMP-1 immunoreactivity was distributed in the extracellular matrix whereas MMP-2, MMP-8 and TIMP-2 immunostaining was present in the epithelium, submucosal glands, vascular endothelium and inflammatory cells in CRS and NP. We suggest that differences in histological features between CRS and NP might be related to the expression of MMP-1, MMP-2, MMP-8 and their tissue inhibitor-2.     

MMP-2、MMP-7、MMP-9、TIMP-1及TIMP-2在乳腺癌组织中的表达及意义

目的:探讨基质金属蛋白酶及其抑制剂在乳腺癌组织中的表达及其与肿瘤浸润转移的关系,为乳腺癌的临床治疗及预后预测提供基础。方法:选择我院2012年5月至2014年5月收治的乳腺癌患者80例,对所选病例的乳腺癌组织、癌旁组织及正常乳腺组织样本进行检测。观察并比较不同乳腺组织中MMP-2,MMP-7、MMP-9、TIMP-1及TIMP-2 m RNA的表达水平。结果:与正常乳腺组织相比较,乳腺癌组织和癌旁组织中MMP-2、MMP-7、MMP-9,TIMP-1及TIMP-2 m RNA的表达显著增加,差异具有统计学意义(P0.05)。乳腺癌组织中MMP-2、MMP-7、MMP-9、TIMP-1及TIMP-2 m RNA的表达显著高于癌旁组织和正常组织,差异具有统计学意义(P0.05)。随着肿瘤范围扩大,MMP-2、MMP-7和MMP-9 m RNA的表达水平显著增加(P0.05),而TIMP-1和TIMP-2 m RNA表达无显著变化(P0.05)。随着淋巴结转移进展,MMP-2、MMP-7和MMP-9 m RNA的表达显著增加(P0.05),而TIMP-1和TIMP-2 m RNA无显著变化(P0.05)。结论:MMP-2、MMP-7、MMP-9、TIMP-1和TIMP-2的m RNA在乳腺癌组织中呈高表达,这可能与乳腺癌的发生和发展有关,而MMP-2、MMP-7和MMP-9可能有助于预测乳腺癌的侵袭行为。     

特布他林联合羧甲司坦片治疗慢性阻塞性肺疾病的疗效及对血清MMP-9、MMP-12、TIMP-1的影响

目的:研究特布他林联合羧甲司坦片治疗慢性阻塞性肺疾病的疗效及对血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶-12(MMP-12)、组织型金属蛋白酶抑制物(TIMP-1)水平的影响。方法:选取2015年3月至2018年2月我院收治的170例COPD患者,根据随机数字法分为观察组(87例)和对照组(83例)。对照组使用特布他林,观察组联合使用羧甲司坦。比较两组患者的临床疗效,治疗前后血清MMP-9、MMP-12、TIMP-1水平,肺功能指标,炎性因子水平的变化及不良反应的发生情况。结果:治疗后,观察组临床总有效率显著高于对照组(P<0.05),血清MMP-9、MMP-12、TIMP-1水平显著低于对照组(P<0.05),最大呼气流速(PEF)、1秒用力呼气容积(FEV1)、用力肺活量(FVC)及FEV1/FVC显著高于对照组(P<0.05),血清肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、中性粒细胞弹性蛋白酶(NE)水平均显著低于对照组(P<0.05)。观察组和对照组不良反应的发生率比较无显著差异(P>0.05)。结论:特布他林联合羧甲司坦片治疗COPD的临床疗效显著优于单用特布他林,且安全性更高,可能与其能有效降低血清MMP-9、MMP-12、TIMP-1水平有关。     

Imbalanced circulating matrix metalloproteinases in polycystic ovary syndrome

Altered levels of matrix metalloproteinases (MMPs) may reflect relevant pathogenetic mechanisms of disease conditions. The objective of this study was to compare the plasma levels of MMPs and tissue inhibitors of MMPs (TIMPs) in polycystic ovary syndrome (PCOS) patients with those found in healthy ovulatory controls and to examine whether the levels of these biomarkers are associated with clinical and biochemical features of this syndrome. Sixty-five healthy ovulatory subjects (controls) and 80 patients with PCOS were include in this study. MMP-2, MMP-8, MMP-9, TIMP-1, TIMP-2 concentrations were measured in plasma samples by gelatin zymography or enzyme-linked immunoassays. MMP-2, MMP-8, MMP-9, and TIMP-1 levels were similar in PCOS patients and in healthy controls (P > 0.05). PCOS patients had lower plasma TIMP-2 levels than healthy controls (P < 0.05). We found higher MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in PCOS patients than in healthy controls (all P < 0.05). Testosterone levels correlated positively with the MMP-9/TIMP-1 ratio and negatively with TIMP-2 levels (r = 0.26, P < 0.01 and r = -0.21, P = 0.02, respectively). In addition, only testosterone was an independent predictor of TIMP-2 levels (estimate = -0.35, P = 0.04) and the MMP-9/TIMP-1 ratio (estimate = 0.01, P = 0.04). We found evidence indicating that the balance between MMPs and TIMPs in women with PCOS is altered, probably due to androgen excess found in these women.     

MMP-2 and TIMP-2 expression,quantitative analysis and biomechanical changes in scar hypertrophy after autologous free transplantation of rabbit oral mucosa and scrotal skin

This study aimed to investigate the long-term scar hypertrophy in the rabbit transplanted oral mucosa and scrotal skin with changed matrix environment, as well as the scar location expression, quantitative analysis of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) and biomechanical changes in the transplanted tissues. The split-thickness skin grafts were collected from the oral mucosas and scrotal skins of 30 male rabbits, and prepared into reelpipes for autologous transplantation into the rabbit back muscular tissues. Samples were collected to carry out elastic tensile mechanical detection and histological observation. The maximum longitudinal tensile displacement of scrotal skin before 8 weeks of transplantation was greater than that after 8 weeks of transplantation (P < 0.05). The expression intensities of MMP-2 and TIMP-2 in the oral mucosa and in scrotal skin at 2 W time point were higher than those at T_o time point (P < 0.05). The expression quantities of TIMP-2 in oral mucosa and scrotal skin during 8–24 W were higher than those of MMP-2 (P < 0.05). At 8 W time point, the TIMP-2/MMP-2 ratio in scrotal skin was higher than that in oral mucosa (P < 0.05). MMP-2 and TIMP-2 expression in normal oral mucosa and scrotal skin is weak, but their expression is remarkably up-regulated after 2 weeks of transplantation, revealing that scar formation was related to the high expression of MMP-2 and TIMP-2. At the 8th–24th weeks, the AOD values of TIMP-2 in oral mucosa and scrotal skin are apparently higher than those of MMP-2; moreover, the TIMP-2/MMP-2 ratio in scrotal skin at the 8th week was higher than that in oral mucosa, which can well explain the earlier scar formation in scrotal skin than in oral mucosa, and it also suggests that the different expression levels between TIMP-2 and MMP-2 may account for the important cause of scar formation.     

经皮椎体成形术对老年骨质疏松性胸腰椎压缩骨折患者血清MMP-3、TIMP-1、IL-6及疗效的影响

目的:探讨经皮椎体成形术对老年骨质疏松性胸腰椎压缩骨折患者血清基质金属蛋白酶-3(MMP-3)、基质金属蛋白酶抑制因子-1(TIMP-1)、白细胞介素-6(IL-6)及疗效的影响。方法:选择60例2016年10月到2017年3月我院接诊的老年骨质疏松性胸腰椎压缩骨折患者,依照随机数表法分为实验组和对照组,每组30例,在都给予常规药物治疗的基础上,对照组给予复位枕垫和康复训练治疗,实验组采用经皮椎体成形术治疗。结果:治疗前,两组血清MMP-3、TIMP-1、IL-6水平无差异(P0.05);治疗后,两组血清MMP-3、IL-6水平均降低,实验组下降幅度更大,两组血清TIMP-1水平均升高,实验组上升幅度更大(P0.05);治疗前,两组患者VAS评分无差异(P0.05),治疗1周及治疗后,实验组患者VAS评分均低于对照组(P0.05);治疗前,两组患者Cobb角无差异(P0.05),治疗后,两组患者Cobb均明显下降,实验组较对照组下降更大(P0.05);治疗前,两组患者伤椎高度比无差异(P0.05),治疗后,两组伤椎高度比明显下降,实验组低于对照组(P0.05);治疗后,实验组有效率96.67%大于对照组的76.67%,差异显著(P0.05)。结论:经皮椎体成形术能有效降低患者血清MMP-3、IL-6水平,恢复TIMP-1水平,能显著提高治疗老年骨质疏松性胸腰椎压缩骨折的疗效     

Alterations in biochemical components of extracellular matrix in intervertebral disc herniation: role of MMP-2 and TIMP-2 in type II collagen loss

Alterations in the composition of intervertebral disc extracellular matrix, mainly collagen and proteoglycans, may cause changes in mechanical properties of the disc, leading to dysfunction, nerve root compression, and herniation with severe clinical manifestations. Matrix metalloproteinases may be involved in degradation by hydrolysing extracellular matrix components. Inhibitors of matrix metalloproteinases, in contrast, function in the maintenance of degradation control. In this study, we investigated: (i) whether the level of matrix degradation correlated with the duration of the symptomatic disease, (ii) roles of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) in intervertebral disc degeneration. Nucleus pulposus of intervertebral discs were obtained from 22 patients and analysed for collagen and proteoglycan contents, and pro-MMP-2, TIMP-2 levels. Collagen content was determined as hydroxyproline and proteoglycan content was measured as glycosaminoglycans. The loss in matrix components did not correlate with the duration of the degenerative disc disease. Pro-MMP-2 levels were higher at early stages of the degenerative disc disease (r = -0.495, P < 0.05). TIMP-2 levels were similar in all samples. Pro-MMP-2 and TIMP-2 levels negatively correlated in herniated discs samples (r = -0.855, P < 0.01). Pro- MMP-2 levels negatively correlated with the collagen content in herniated disc material. Our findings may suggest a silent period of active disease prior to symptomatic outcome during which irreversible matrix loss occurs. Involvement of other proteolytic enzymes at different stages of the disease should also be investigated to help to control the degradation cascade at relatively early stages of disc degeneration before the clinical onset of disease.     

ATP stimulates MMP-2 release from human aortic smooth muscle cells via JNK signaling pathway

Aortic smooth muscle cell release of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) has been implicated in aortic aneurysm pathogenesis, but proximal modulation of release is poorly understood. Extracellular nucleotides regulate vascular smooth muscle cell metabolism in response to physiochemical stresses, but nucleotide modulation of MMP and/or TIMP release has not been reported. We hypothesized that nucleotides modulate MMP-2 and TIMP-2 release from human aortic smooth muscle cells (HASMCs) via distinct purinergic receptors and signaling pathways. We exposed HASMCs to exogenous ATP and other nucleotides with and without interleukin-1beta (IL-1beta). HASMCs were pretreated in some experiments with apyrase, which degrades ATP, and inhibitors of ERK1/2, JNK, and p38 MAPK. MMP-2 and TIMP-2 released into supernatant were assessed using ELISA and Western blotting. ATP, adenosine, and UTP significantly stimulated MMP-2 release in the presence of IL-1beta (300 nM ATP: 181 +/- 22%, P = 0.003; 30 microm adenosine: 244 +/- 150%, P = 0.001; and 200 microm UTP: 153 +/- 40%, P = 0.015; vs. 100% constitutive). ATP also stimulated MMP-2 release in the absence of IL-1beta (100 microm ATP: 148 +/- 38% vs. 100% constitutive). Apyrase significantly reduced ATP-stimulated MMP-2 release (apyrase + 500 nM ATP: 59 +/- 3% vs. 124 +/- 7% with 500 nM ATP). Rank-order agonist potency for MMP-2 release was consistent with ATP activation of PAY and PAY receptors. ATP induced phosphorylation of intracellular JNK, and inhibition of the JNK pathway blocked ATP-stimulated MMP-2 release, indicating signaling via this pathway. Nucleotides are thus novel stimulants of MMP-2 release from HASMCs and may provide a mechanistic link between physiochemical stress in the aorta and aneurysms, especially in the context of inflammation.     

博莱霉素致肺间质成纤维细胞MMP-2/TIMP-1表达失衡

观察博莱霉素对肺间质成纤维细胞中基质金属蛋白酶-2（MMP-2）及组织金属蛋白酶抑制剂-1（TIMP-1）表达的影响,探讨博莱霉素引起肺纤维化的机制。体外培养肺间质成纤维细胞,并向培养基中加入博莱霉素,在作用不同时间后收集样本,采用酶谱图测定细胞培养上清液中MMP-2酶活性、ELISA测定TIMP-1量,免疫组织化学法检测细胞中MMP-2、TIMP-1的原位表达,RT-PCR法检测MMP-2和TIMP-1的mRNA水平。结果发现,博莱霉素在2h、12h促进MMP-2的分泌,24h后无促分泌作用;而2-48h,MMP-2的原位表达及mRNA均不受博莱霉素的影响;博莱霉素从12h开始促进TIMP-1及mRNA的表达,并持续至48h。结果表明博莱霉素可引起肺间质戍纤维细胞MMP-2／TIMP-1表达失衡,并可能参与肺纤维化的发生。     

脑出血大鼠血肿周围脑组织含水量与MMP-9、IL-6及TIMP-1表达水平的相关性研究

目的:研究脑出血(ICH)大鼠血肿周围脑组织含水量与基质金属蛋白酶-9(MMP-9)、白细胞介素-6(IL-6)及组织基质金属蛋白酶抑制剂-1(TIMP-1)表达水平的相关性。方法:84只健康成年雄性Wistar大鼠按随机数字表法分成观察组、假手术组以及对照组,每组28只。另将观察组分成ICH后1d亚组9只,3d亚组9只,7d亚组10只。观察组大鼠实施ICH模型的制备,假手术组的大鼠仅给予空针穿刺,对照组不进行模型制备。检测并对比各组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平,对比观察组内不同亚组(ICH后1d、3d、7d)血肿周围的脑组织含水量、MMP-9、IL-6和TIMP-1水平,并分析ICH大鼠血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1表达水平的相关性。结果:观察组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平均分别高于假手术组及对照组,差异均有统计学意义(P0.05)。观察组内3d和7d亚组血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1水平均分别高于1d亚组,但7d亚组低于3d亚组,差异均有统计学意义(P0.05)。根据Spearman相关性分析结果显示,ICH大鼠血肿周围的脑组织含水量与MMP-9、IL-6、TIMP-1表达水平均呈正相关(P0.05)。结论:ICH大鼠的血肿周围脑组织含水量与MMP-9、IL-6及TIMP-1表达水平均呈正相关,MMP-9、IL-6、TIMP-1在ICH后周围组织水肿的发生、发展中具有重要作用。     

基于"经筋理论"针刀治疗对早中期膝骨关节炎患者骨代谢指标和血清TIMP-1、MMP-3、MMP-13的影响

摘要 目的：探讨基于"经筋理论"针刀治疗对早中期膝骨关节炎（KOA）患者骨代谢指标和血清金属蛋白酶抑制物-1（TIMP-1）、基质金属蛋白酶（MMP）-3、MMP-13的影响。方法：根据随机数字表法,将2021年1月至2023年1月期间就诊于新疆医科大学附属第一医院的120例早中期KOA患者分为对照组（n=60,常规治疗）和研究组（n=60,对照组的基础上接受"经筋理论"针刀治疗）。对比两组疗效、量表评分[疼痛视觉模拟评分（VAS）、西安大略和麦克马斯特大学骨关节炎调查表（WOMAC）]、骨代谢指标[抗酒石酸盐酸性磷酸酶异构体（TRACP-5b）、骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）]和血清TIMP-1、MMP-3、MMP-13。结果：与对照组相比,研究组的临床总有效率更高（P<0.05）。与对照组相比,研究组治疗后WOMAC、VAS评分和血清MMP-3、MMP-13、TRACP-5b水平更低,TIMP-1、BALP、BGP水平更高（P<0.05）。结论：基于"经筋理论"针刀治疗早中期KOA患者,可有效减轻疼痛症状,提高临床治疗效果,可能与改善骨代谢指标和血清TIMP-1、MMP-3、MMP-13水平有关。     

通痹胶囊治疗类风湿关节炎的疗效及对微循环和血清MMP-1、MMP-3的影响

目的:探讨通痹胶囊治疗类风湿关节炎(RA)的疗效及对微循环指标和基质金属蛋白酶-1(MMP-1)、血清基质金属蛋白酶-3(MMP-3)的影响。方法:选取2016年1月～2018年9月期间我院收治的90例RA患者,按照随机数字表法分为研究组(n=45)、对照组(n=45)。对照组患者给予来氟米特、甲氨蝶呤常规治疗,研究组在对照组基础上联合通痹胶囊治疗,比较两组患者疗效、治疗前后的微循环指标[血管阻力指数(RI)、舒张期峰值速度(EDV)以及收缩期峰值速度(PSV)]、MMP-1、MMP-3、类风湿因子滴度(RF)、C反应蛋白(CRP)、红细胞沉降率(ESR)、抗链球菌溶血素"O"(ASO),记录两组治疗期间不良反应发生情况。结果:研究组治疗4个月后的临床总有效率高于对照组(P0.05)。两组患者治疗4个月后RI、MMP-1、MMP-3、CRP、RF、ESR、ASO下降,且研究组低于对照组(P0.05);EDV、PSV升高,且研究组高于对照组(P0.05)。两组患者不良反应发生率比较无差异(P0.05)。结论:在常规治疗的基础上联合通痹胶囊可有效缓解RA病情,改善机体微循环,降低血清MMP-3、MMP-1水平,且用药安全性较好。     

肺力咳胶囊联合布地奈德福莫特罗粉吸入剂对慢性阻塞性肺疾病急性加重期患者血气分析指标和MMP-9/TIMP-1失衡的影响

摘要 目的：探讨肺力咳胶囊联合布地奈德福莫特罗粉吸入剂对慢性阻塞性肺疾病急性加重期（AECOPD）患者血气分析指标和基质金属蛋白酶-9（MMP-9）/金属蛋白酶抑制物-1（TIMP-1）失衡的影响。方法：选取皖南医学院附属铜陵市人民医院2019年4月~2022年7月期间收治的AECOPD患者81例。按照随机数字表法,将患者分为对照组（40例,接受布地奈德福莫特罗粉吸入剂治疗）和研究组（41例,接受肺力咳胶囊联合布地奈德福莫特罗粉吸入剂治疗）。对比两组临床症状改善情况、肺功能指标、MMP-9/TIMP-1相关指标、血气分析指标,观察两组不良反应发生率。结果：研究组的临床症状缓解时间均短于对照组（P<0.05）。治疗14 d后,两组第1秒用力呼气容积（FEV₁）、用力肺活量（FVC）、FEV₁/FVC升高,且研究组较对照组更高（P<0.05）。治疗14 d后,两组血氧饱和度（SpO₂）、血氧分压（PO₂）升高,血二氧化碳分压（PCO₂）下降,且研究组变化较对照组幅度更大（P<0.05）。治疗14 d后,两组血清MMP-9、TIMP-1水平及MMP-9/TIMP-1均下降,且研究组较对照组更低（P<0.05）。两组不良反应发生率对比无差异（P>0.05）。结论：布地奈德福莫特罗粉吸入剂联合肺力咳胶囊治疗对AECOPD患者,有助于临床症状的缓解,改善肺功能和血气分析指标,调节MMP-9/TIMP-1失衡。