Objective To determine the contents of matrix metalloproteinase 3 (MMP-3) and interleukin 1 (IL-1) in the tissues of the lumbar disc herniation and to investigate their roles in the pathogenesis. Methods The tissues of the herniated lumbar disc were obtained from 30 patients undergoing surgery for persistent radiculopathy from June 2003 to December 2004 and at the same time these samples were divided into the following three experimentalgroups: the bulge group (n=11), the protrusion group (n=9), and the prolapsus group (n=10)，14 males, 16 females, aged 33.64 years. As the control group, 9 lumbar disc specimens were harvested from 9 patients(4 males, 5 females, aged 21-58 years) suffering from bursting fracture of the lumbar spine. The specimens were analyzed by the ELISA method for the contents of MMP-3 and IL-1. Results The contents of MMP-3(14.25±1.32, 19.89±2.97,20.69±2.18 ng/ml in the bulge group, protrusion group and prolapsus group, separately) and IL-1(8.52±0.22， 11.88±0.52，11.90±0.73 pg/ml in the bulge group, protrusion group and prolapsus group, separately) in the experimental groups were significantly higher than those in the control group. The contents of MMP-3 and IL-1 in the protrusion group were not significantly higher than those in the prolapsus group, but they were significantly higher than those in the bulge group(P＜0.01). The contents of MMP-3 had a significant relationship with the contents of IL-1 in the three experimental groups and the control group(P＜0.01). Conclusion The result demonstrates that the tissues of the lumbar disc herniation can produce both MMP-3 and IL-1, which may have an unknown but important relationship with each other.
Objective To study the relationship between metalloproteinases (MMPs) and breast cancer. Methods The literature in recent years on the relationship between the expression of MMPs and breast cancer was reviewed. Results The balance between MMPs and tissue inhibitors of metalloproteinases (TIMPs) is keeping normally kept in human body. Many of the studies showed that the expression of MMPs is increased in breast cancer. Conclusion The growth, invasion and metastasis of breast cancer is closely related with the increased expression of MMPs. This suggests that MMPs is a valuable prognostic marker and TIMPs would be a novel drug against cancer.
Purpose To identify matrix metalloproteinase (MMP) in human vitreous samples of diabetic vitreoretinopathy (DR) and other ocular diseases (non-DR) and to probe the related factors of MMP expression． Methods Thirty-one diabetic and 17 non-diabetic vitreous samples (nine macular hole and eight epiretinal membrane patients) were examined． Samples were concentrated and subjected to substrate zymography to conduct a quantitative analysis of MMP-2,9 activity． The technology of Western blotting against anti-human MMP-2,9 was performed to identify MMP in vitreous samples． Results Vitreous samples both from DR patients and from non-DR patients showed a single band at the position of 72 kDa, correspondin g to MMP-2． Quantitative analysis revealed that diabetic vitreous showed higher MMP-2 activity than non-DR, although the difference was not significant.45.2% of DR patients showed MMP-9, but no expression in non-DR．Among DR samples, the positive ratio of MMP-9 in partial posterior vitreous detachment (PVD)(66．7%) was significantly higher than that of complete PVD (15．4%)． Western blotting study confirmed the expression of MMP-2 and MMP-9． Conclusion There is no obvious difference of MMP-2 activity between DR and non-DR． MMP-9 may be involved in the pathogenesis of diabetic vitreor etinopathy and the deterioration of proliferative change． (Chin J Ocul Fundus Dis, 2001,17:195-197
Objective To explore the effects of overexpression of human tissue inhibitors of metalloproteinase-1 (hTIMP-1) on proliferation of human liver cancer cell line HepG2 in vitro. Methods A recombinant adenoviral vector containing full-length cDNA of hTIMP-1 was generated and transfected into HepG2. The viral titer was checked by measuring GFP, and the expression of hTIMP-1 in vitro was detected by the techniques of Western blot and semi-quantitative RT-PCR. The ultrastructure was observed by transmission electron microscope and the effects of overexpression of hTIMP-1 on proliferation of HepG2 in vitro was analyzed by MTT assay and growth curve. Results The resultant AdhTIMP-1 was successfully constructed and the expression of hTIMP-1 was detected by Western blot and RT-PCR. The growth and proliferation of HepG2, which had been transfected with AdhTIMP-1, was significantly inhibited. Conclusion The proliferation of HepG2 was markedly inhibited by recombinant adenovirus-mediated overexpression of hTIMP-1, which may pave the way for further application in liver gene therapy.
【 Abstract 】 Objective Overexpressions of epidermal growth factor (EGF) and EGF receptor have been associated with progression and invasive phenotype of pancreatic cancer. However, the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood. In this study, effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated. Methods The effects of EGF on the proliferation, adhesion and invasion of pancreatic cancer cells were detected by WST-1 proliferation assay, adhesion assay and invasive assay, respectively. The activity and expression of MMP-2 and MMP-9 were examined by zymography, Western blot and RT-PCR, respectively. The activity of NF- κ B was examined by EMSA. Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion. The expressions of NF- κ B and MMP-9 were significantly increased by EGF, but EGF did not affect the activity and expression of MMP-2. Furthermore, EGF stimulated the NF- κ B binding activity. Pretreatment with NF- κ B inhibitors, pyrrolidine dithiocarbamate (PDTC), could significantly inhibit the activity of NF- κ B induced by EGF. Meanwhile, the EGF-induced expression and activity of MMP-9, as well as cell invasiveness were also inhibited by NF- κ B inhibitor. Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF- κ B in pancreatic cancer cells, which implies that NF- κ B inhibitant, such as PDTC, may diminish the invasiveness of pancreatic cancer cells.
Objective To evaluate the effect of smooth muscle cell transplantation on myocardial interstitial reconstruction shortly after myocardial infarction. Methods A total of 48 female Wister rats were randomly divided into two groups with the random number table, the control group (n=24) and the smooth muscle cell transplantation group (n=24). The left coronary artery was ligated to set up the myocardial infarction animal model. An amount of 05 ml phosphate buffered saline(PBS) containing 1×106 smooth muscle cells or 0.5 ml PBS without cells was injected into the injured myocardium immediately. By immunoblot and reverse transcriptionolymerase china reaction (RT-PCR), we observed the amount of protein and mRNA of matrix metalloproteinase2(MMP-2), matrix metalloproteinase-9(MMP-9) and tissue inhibitor of metalloprotease-3 (TIMP-3) in the myocardium of the rats. Results The transplanted smooth muscle cells survived well. Compared with the control group, myocardial TIMP3 mRNA (1.06±0.22 vs. 0.81±0.19, t=－2.358, P=0.033) and protein content (3.33±0.53 vs. 1.63±0.47, t=－6.802, Plt;0.001) were significantly increased in the transplantation group. Myocardial MMP-2, MMP-9 mRNA (0.49±0.12 vs. 1.16±0.18, t=8.453, Plt;0.001; 0.45±0.12 vs. 0.80±0.11, t=5.884, Plt;0.001) and protein content (3.98±1.08 vs. 6.05±0.91, t=4.139, P=0.001; 0.39±0.14 vs. 0.57±0.17, t=2.409, P=0.031) [CM(1585mm]were significantly reduced in the transplantation group compared with the control group. Conclusion transplanted smooth muscle cells can survive well in the infarction myocardium and can increase the amount of myocardial TIMP-3 mRNA and protein content and reduce myocardial MMP-2, MMP-9 mRNA and protein content, which is an effective way to prevent harmful cardiac remodeling.
目的 探讨不同剂量和不同疗程米非司酮对大鼠子宫异位内膜基质金属蛋白酶-9（MMP-9）及其组织特异性抑制物-1（TIMP-1）表达的影响。 方法 65只子宫内膜异位症大鼠随机分为低剂量组、高剂量组、对照组。各个剂量组分别灌胃20、30、40 d后取异位子宫内膜组织用免疫组织化学法检测MMP-9及TIMP-1的表达，并计算MMP-9/TIMP-1比值。 结果 低剂量组和高剂量组均能使异位内膜MMP-9表达下降（P＜0.05）,TIMP-1表达升高（P＜0.05）,高剂量组的作用更加明显，与低剂量组差异有统计学意义（P＜0.05）；用药30 d低剂量组TIMP-1表达最高，与用药20 d和40 d相比差异有统计学意义（P＜0.05）,同样高剂量组用药30d TIMP-1的表达也最高，与用药20 d和用药40 d比较差异有统计学意义（P＜0.05）。与用药20、40 d比较差异有统计学意义（P＜0.05）。 结论 米非司酮能够降低大鼠异位子宫内膜的侵袭能力，高剂量米非司酮抑制效果更明显；用药30 d米非司酮对大鼠异位内膜的侵袭能力抑制最强，延长用药时间不能使异位内膜侵袭能力继续下降。
目的 研究缺氧诱导因子-1α（HIF-1α）与基质金属蛋白酶-2（MMP-2）在低分化胃癌中的表达，并探讨两者在低分化胃癌浸润、转移过程中的相互关系及作用。方法 采用SP免疫组化方法，检测54例低分化胃癌及20例正常胃组织石蜡标本中HIF-1α和MMP-2蛋白表达水平。结果 低分化胃癌组织中HIF-1α和MMP-2蛋白表达阳性率明显高于正常胃组织（Plt;0.05）。两者的表达与肿瘤的浸润深度、淋巴转移和TNM分期均有关（Plt;0.05），HIF-1α与MMP-2的表达呈正相关（r=0.580, Plt;0.05）。结论 HIF-1α和MMP-2在低分化胃癌的侵袭、转移过程中存在一定的协同作用，两者可能成为判断胃癌预后的指标。
ObjectiveTo summarize the biological function of extracellular matrix metalloproteinase inducer (EMMPRIN) in tumor progression, and its roles in clinical diagnosis and treatment in recent years. MethodsLiteratures about the recent studies on molecular structure of EMMPRIN and biological function in tumor progression were reviewed according to the results searched from PubMed database. ResultsEMMPRIN play important roles in the tumor progression, involved in inducing the degradation of extracellula matrix, promoting angiogenesis, inhibiting apoptosis, enhancing chemoresistance and so on. ConclusionEMMPRIN could be a potential therapeutic target in turmor.
Abstract: Objective To study the pathophysiological mechanism of the morphological change of immature pulmonary vessels in the piglet model of congenital heart defect with decreased pulmonary blood flow established with balloon atrial septostomy and pulmonary artery banding. Methods Twenty piglets at an age of one to two months were divided into three groups with random number table. For the control group (group C,n=6), small incisions were carried out on the right chest to produce a transient reduction in the pulmonary blood; for the lowmedium pulmonary artery stenosis group (group T1, n=7), the balloon dilator was delivered through the surface of the right atrium and septostomy and pulmonary artery banding were performed, and the systolic transpulmonary artery banding pressure (Trans-PABP) was controlled to be 20.30 mm Hg; For the severe pulmonary artery stenosis group (group T2, n=7), the same surgical procedures with group T1 were performed while TransPABP was controlled to be more [CM(159mm]than 3050 mm Hg.At 2 months after surgery respectively,a lung tissue of 1.0 cm×0.8 cm×0.8 cm from the lateral segment of the right middle lobe was taken out to be observed under optic microscope. The morphological change of the distal arterioles was detected. Furthermore, the content of vascular endothelial growth factor (VEGF) and matrix metalloproteinase2( MMP2) were also examined by the method of enzymelinked immunosorbent assay (ELISA). Results The model was successfully established in all the survival piglets of the group T1 and group T2. Two months after operation, the inner diameter of the pulmonary arterioles in group T1 was significantly higher than that in group C (82.89±10.72 μm vs.74.12±9.28 μm;t=－5.892, Plt;0.05), so as group T2 (85.47±5.25 μm vs.74.12±9.28 μm;t=-6.325, Plt;0.05); the number of arterioles per square centimeter (NAPSC) of group T1 was significantly lower than that of the group C (229.70±88.00 entries/cm 2 vs. 431.50±40.60 entries/cm2; t=39.526, Plt;0.05), so as group T2 (210.00±40.30 entries/cm2 vs. 431.50±40.60 entries/cm2; t=67.858, Plt;0.05). Two months after operation, the lung expression of MMP -2 and VEGF in group T1 was significantly lower than that in group C (58.30±19.60 ng/ml vs. 81.20±16.70 ng/ml, t=14.261, Plt;0.05; 17.80±3.00 pg/ml vs. 21.40±3.80 pg/ml, t=8.482, P＜0.05), so does group T2 (42.10±15.20 ng/ml vs. 81.20±16.70 ng/ml, t=27.318, P＜0.05; 12.30±3.20 pg/ml vs. 21.40±3.80 pg/ml, t=15.139, P＜0.05). Conclusion Structural remodeling of pulmonary extracellular matrix is an important feature of the piglet model of congenital heart defect with decreased pulmonary blood flow. The arterioles show significant hypoplasia or degradation. Change in the structural proteins and cytokines during the reduction of blood in the lung is the key to structural remodeling.