微创术对脑出血后脑水肿患者血浆明胶酶B的影响

目的探讨高血压性脑出血微创术对清除血肿后脑水肿患者血浆明胶酶B(MMP-9)的影响。方法127例脑出血患者随即分为内科治疗组60例、微创术血肿抽吸引流组67例;采用酶联免疫法(ELISA)测定脑出血后第3天、第7天和第21天血浆MMP-9含量。结果微创组和内科治疗组血浆中MMP-9含量均升高;两组治疗后第3、7天的含量与治疗前(发病24h内)比较,差异有统计学意义(P<0.05);两组治疗后不同时间点血浆中MMP-9含量比较,差异有统计学意义(P<0.05)。结论微创组能减少患者血浆MMP-9含量的增加。     

低频电磁场对大鼠主动脉平滑肌细胞基质金属蛋白酶的影响

目的 观察不同磁场强度及作用时间的低频电磁场（LFEMF）对培养的大鼠主动脉血管平滑肌细胞（VSMC）表达基质金属蛋白酶-2（MMP-2）的影响。方法 用含10％小牛血清的DMEM培养液体外培养大鼠主动脉VSMC，随机分为对照组、LFEMF不同磁场强度（20，40，60mT）及时间（10，20，30min）干预组，运用MMP-2活性酶图分析法结合光密度扫描分析，观察LFEMF对VSMC的MMP-2表达的影响。结果 不同磁场强度组均明显抑制MMP-2的活性，且具有剂量依赖性，但抑制作用不随时间延长而变化，不具有时间依赖性。结论 适当强度和作用时间的LFEMF抑制VSMC的MMP-2活性的表达，磁场对经皮腔内冠状动脉成形术（PTCA）及支架植入术后的再狭窄（RS）可能具有防治作用。     

结缔组织生长因子通过ERK1/2和PI3K信号通路促进大鼠肝星状细胞迁移和基质金属蛋白酶2表达

目的：研究结缔组织生长因子（CTGF）对大鼠肝星状细胞（HSC）迁移及基质金属蛋白酶2（MMP-2）表达及活化的影响。方法分别应用RT-PCR和Western blotting法检测MMP-2表达,明胶酶谱法检测MMP-2的活性;运用Western blotting法检测ERK1/2和Akt的磷酸化水平。运用Transwell小室检测肝星状细胞迁移能力。结果 CTGF呈剂量依赖性促进大鼠HSC中MMP-2 mRNA和蛋白表达;同时CTGF能够促进HSC迁移,MMP-2特异性抑制剂能够抑制CTGF的促迁移作用。ERK1/2和PI3K抑制剂能够显著抑制CTGF诱导的MMP-2表达以及CTGF促进HSC的迁移作用。结论 MMP-2表达和活性的增强在CTGF促进HSC迁移过程中发挥着重要作用,ERK1/2和PI3K信号通路在CTGF促进MMP-2表达发挥关键作用。     

UHMWPE 颗粒上调 EMMPRIN、MMPs 表达并增强共培养体系中 THP-1、FLS 迁移、侵袭能力的实验研究

目的：探讨超高分子量聚乙烯（ UHMWPE）颗粒对人单核细胞株THP-1、成纤维样滑膜细胞（ FLS）共培养体系迁移、侵袭能力及对细胞外基质金属蛋白酶诱导剂（ EMMPRIN）与基质金属蛋白酶（ MMPs）表达的影响。方法建立THP-1-FLS细胞共培养体系,应用台盼蓝染色检测THP-1细胞、FLS细胞存活率,Western blot、明胶酶谱、实时定量PCR方法检测样品中的EMMPRIN、MMP-2、MMP-9的表达及活性,并应用RNA干扰技术评估EMMPRIN的作用。结果 UHMWPE颗粒刺激THP-1细胞EMMPRIN表达上调,对FLS的EMMPRIN表达无明显影响。 UHMWPE颗粒刺激FLS的MMP-2、MMP-9表达上调、活性增强,对 THP-1表达 MMPs 无明显影响。 THP-1-FLS 共培养时, UHMWPE颗粒刺激使EMMPRIN、MMP-2、MMP-9表达上调更为显著。颗粒刺激下,THP-1-FLS共培养体系的迁移能力、侵袭能力明显强于无颗粒刺激,并与EMMPRIN的表达水平和MMPs的活性呈明显正相关。行THP-1细胞EMMPRIN基因干扰后,共培养体系的EMMPRIN、MMPs表达均下调,迁移、侵袭能力下降。结论 UHMWPE 颗粒可刺激THP-1-FLS 共培养体系高表达EMMPRIN,上调MMP-2、MMP-9的分泌并增强其活性,提高共培养体系的迁移、侵袭能力。     

Ovine forestomach matrix biomaterial is a broad spectrum inhibitor of matrix metalloproteinases and neutrophil elastase

Proteases play a critical role in the ordered remodelling of extracellular matrix (ECM) components during wound healing and tissue regeneration. However, the usually ordered proteolysis is compromised in chronic wounds due to over‐expression and high concentrations of matrix metalloproteinase's (MMPs) and neutrophil elastase (NE). Ovine forestomach matrix (OFM) is a decellularised extracellular matrix‐based biomaterial developed for tissue regeneration applications, including the treatment of chronic wounds, and is a heterogeneous mixture of ECM proteins and proteoglycans that retains the native structural and functional characteristics of tissue ECM. Given the diverse molecular species present in OFM, we hypothesised that OFM may contain components or fragments that inhibit MMP and NE activity. An extract of OFM was shown to be a potent inhibitor of a range of tissue MMPs (IC₅₀s = 23 ± 5 to 115 ± 14 µg/ml) and NE (IC₅₀ = 157 ± 37 µg/ml), and was more potent than extracts prepared from a known protease modulating wound dressing. The broad spectrum activity of OFM against different classes of MMPs (i.e. collagenases, gelatinases and stromelysins) may provide a clinical advantage by more effectively addressing the protease imbalance seen in chronic wounds.     

2型糖尿病脑梗死患者血清MMP-2、TIMP-1的测定及临床意义

目的:观察2型糖尿病脑梗死患者血清基质金属蛋白酶-2(matrixmetalloproteinase-2,MMP-2)及其抑制因子基质金属蛋白酶抑制因子-1(tissueinhibitorsofmatrixmetalloproteinase-1,TIMP-1)的含量变化,探讨其在脑梗死发生发展过程中的作用和意义。方法:用ELISA法检测39例2型糖尿病脑梗死患者发病24h,以及32例2型糖尿病非脑梗死患者、26例非糖尿病脑梗死组、36例健康体检者血清MMP-2和TIMP-1的含量。结果:2型糖尿病脑梗死患者血清MMP-2、TIMP-1水平显著高于2型糖尿病非脑梗死组、非糖尿病脑梗死组、对照组(P<0·05)。2型糖尿病脑梗死发病24h的血清MMP-2水平与空腹血糖、糖化血红蛋白(HbA1c)正相关(r=0·286,r=0·327);2型糖尿病脑梗死发病24h血清TIMP-1水平与空腹血糖呈正相关(r=0·271),与HbA1c呈正相关(r=0·373)。与神经功能缺损程度评分(脑卒中分值)、总胆固醇、甘油三脂均无明显相关性(P>0·05)。结论:2型糖尿病脑梗死患者血清MMP-2和TIMP-1水平增高且与血糖水平呈正相关,MMP-2和TIMP-1在2型糖尿病脑梗死发病过程中起着重要的作用。     

High levels of soluble GPR56/ADGRG1 are associated with positive rheumatoid factor and elevated tumor necrosis factor in patients with rheumatoid arthritis

Background

GPR56/ADGRG1 is a member of the adhesion-class G protein-coupled receptor (aGPCR) family important in brain development, oncogenesis and tumor metastasis. Like other aGPCRs, GPR56 is cleaved at the GPCR proteolysis site (GPS) motif into an N-terminal fragment (NTF) and a C-terminal fragment (CTF). Existence of soluble GPR56 (sGPR56) has been shown in vitro, however the underlying mechanism and its pathophysiologic role remains undetermined.