血吸虫肝纤维化中基质金属蛋白酶及抑制剂的表达

目的观察基质金属蛋白酶(MMP)-13,基质金属蛋白酶组织抑制剂(TIMP)-3及α-平滑肌肌动蛋白(α-SMA)在晚期日本血吸虫病家兔肝脏和正常家兔肝脏中的表达。方法应用免疫组织化学和半定量Western免疫印迹方法检测了血吸虫病肝纤维化模型家兔42只及正常家兔8只中的MMP-13、TIMP-3、α-SMA的表达。结果正常对照组的MMP-13、TIMP-3、α-SMA的表达分别是(3.20±0.45)、(0.76±0.32)、(0.92±0.28)%;血吸虫病纤维化肝脏中的MMP-13、TIMP-3、α-SMA的表达分别是(10.56±3.62)、(6.50±2.56)、(5.78±2.98)%,较正常对照组明显增加(P<0.01),主要表达于成纤维细胞,肌成纤维细胞中,以纤维间隔及汇管区最明显,且三者来源定位基本一致。结论在血吸虫病肝纤维化中,成纤维细胞及肌成纤维细胞是MMP-13、TIMP- 3、α-SMA表达的主要细胞,TIMP-3的表达增高在肝纤维化的发生、发展中具有重要作用。     

川崎病患儿基质金属蛋白酶-9及其组织抑制物-1血清水平变化的临床意义

目的通过对川崎病(KD)患儿血清基质金属蛋白酶(MMP)-9及其抑制物组织基质金属蛋白酶抑制物(TIMP)-1水平的测定,探讨MMP-9 及TIMP-1与川崎病发病及其冠状动脉并发症发生发展的关系.方法采用酶联免疫吸附检测(ELISA)法对30例KD无冠状动脉病变(CAL)及9例KD合并CAL患儿急性期和恢复期血清MMP-9、TIMP-1水平进行检测,并与15例其他发热性疾病患儿及18例正常健康儿童进行对照.结果急性期KD有CAL组和无CAL组血清MMP-9、TIMP-1、MMP-9/TIMP-1分别是896.2±81.7、342.6±43.1、2.5±0.6和284.3±40.9、389.5±20.8、0.8±0.2,均较发热对照组及正常对照组(87.9±18.9、251.5±13.0、0.3±0.1和24.6±2.8、90.0±4.2、0.3±0.02)明显增加(P<0.01),且有CAL组的MMP-9及MMP-9/TIMP-1较无CAL组增高更为显著(P<0.01);恢复期KD无CAL组患儿血清MMP-9、TIMP-1、MMP-9/TIMP-1降至正常水平(26.4±7.6、95.6±5.8、0.2±0.1),而有CAL组患儿虽较急性期亦明显下降(220.0±28.3、258.9±15.0、0.9±0.3),但仍然明显高于正常对照组(分别P<0.01和P<0.05),发热对照组血清MMP-9及TIMP-1水平亦较正常对照组明显增高(P<0.01),但其MMP-9/TIMP-1与正常对照组比较差异无显著性(P>0.05).结论 MMP-9及TIMP-1参与了川崎病的病理生理过程,血清MMP-9升高及MMP-9/TIMP-1持续失衡可能与川崎病冠状动脉炎及动脉瘤的形成有关.     

基质金属蛋白酶-9及金属蛋白酶组织抑制剂-1对甲状腺乳头状癌诊断的意义

目的:探讨基质金属蛋白酶-9(MMP-9)和金属蛋白酶组织抑制剂-1(TIMP-1)在甲状腺肿瘤组织中的表达。方法:制备组织芯片,采用免疫组织化学和原位杂交技术检测56例甲状腺癌组织、56例癌旁组织和40例良性甲状腺病变组织中MMP-9和TIMP-1的表达情况。结果:MMP-9和TIMP-1蛋白在甲状腺癌组织的阳性表达率为71.4%和57.1%,MMP-9 mRNA和TIMP-1 mRNA在甲状腺癌组织中阳性表达率为67.9%和62.5%,均明显高于癌旁和良性甲状腺病变组织(P<0.05)。在甲状腺癌组织中,MMP-9、TIMP-1蛋白和MMP-9、TIMP-1 mRNA的表达,分别呈负相关性(RS=-0.309、-0.264,P<0.05)。结论:MMP-9和TIMP-1在组织中的检测有助于甲状腺癌的判断,并可作为预后评估的重要参考。     

Clinical significance of tissue inhibitor of metalloproteinase and matrix metalloproteinase mRNA expression in thymoma

BACKGROUND: Matrix metalloproteinases (MMPs) are proteolytic enzymes which degrade extracellular matrix and basement membrane. There is much evidence that their increased expression is correlated with tumor aggressiveness in various carcinomas. Tissue inhibitor of metalloproteinases (TIMPs) are the specific inhibitors of MMPs. MMPs and TIMPs are considered to play an important role in carcinoma invasion and metastasis. We hypothesized that MMPs and TIMPs also play an important role in thymoma. MATERIALS AND METHODS: This study included 34 thymoma cases. The mRNA levels of MMP-1, -7, and -9, TIMP-1 and -2, and GAPDH were quantified by real-time polymerase chain reaction using LightCycler. We also performed immunohistochemistry for TIMP-1. RESULTS: The TIMP-1/GAPDH mRNA expression level was significantly higher in invasive (stage II-IV) thymomas (means +/- SE, 81.4 +/- 28.1) than in noninvasive (stage I) thymomas (30.9 +/- 8.3, P = 0.026). The MMP-1/GAPDH mRNA expression level was also higher in invasive thymomas (19.7 +/- 7.5) than in non invasive thymomas (2.26 +/- 1.72, P = 0.020). Immunopositivity of TIMP-1 was localized in stromal cells adjacent to the advancing margin of the tumor. CONCLUSIONS: These findings suggest that TIMPs and MMPs play an important role in the invasion of thymoma.     

Presence of matrix metalloproteinases and tissue inhibitor of matrix metalloproteinase in human sperm

The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade protein components of the extra-cellular matrix. The necessity of breakdown of physical barriers in the fertilization process suggests that MMPs, along with their tissue inhibitors (TIMPs), might be involved in this task. We have examined the presence of MMP and TIMP in normal and abnormal human sperm samples by gel zymography and Western blot analysis. Thirty-five normal sperm samples and 35 abnormal sperm samples were examined in this study. Gel zymography showed 92-, 72-, 62-, and 28-kd molecular-weight bands exhibiting gelatin-degrading activity in both normal and abnormal sperm samples. The 92-, 72-, and 62-kd bands with gelatinolytic activity are consistent with pro-MMP-9, pro-MMP-2, and active MMP-2, respectively (pro-MMP being the zymogen of MMP). Western blot analysis showed the presence of TIMP-1 in both normal and abnormal sperm samples. A higher 28-kd activity and a lower 92-kd MMP activity in normal sperm samples relative to abnormal samples were detected. No marked difference in TIMP-1, 72-kd, and 62-kd release was observed between normal and abnormal sperm samples. In conclusion, this is the first report of MMP activity in normal and abnormal human sperm samples and of TIMP presence in sperm samples. The data indicate a different MMP profile between normal and abnormal sperm samples, with a higher 28-kd activity and a lower 92-kd MMP activity in normal relative to abnormal samples.     

Remodeling of experimental arteriovenous fistula with increased matrix metalloproteinase expression in rats

OBJECTIVE: Venous dilatation and wall thickening are part of the maturation of an arteriovenous fistula (AVF). However, the underlying mechanism of AVF remodeling remains unknown. We therefore studied whether matrix remodeling elicited by matrix metalloproteinases (MMPs) may contribute to AVF maturation. METHODS: A femoral AVF model in rats was established by invagination of the distal end of the left femoral artery into the femoral vein after venotomy (fistula group). In the sham group, the left femoral artery was cut, but venous invagination was not performed. Changes in the hemodynamics and the diameter of the iliac vein were studied on days 3, 14, and 28, then the iliac vein was removed and examined for changes in wall thickness and expression of MMP-2 and MMP-9, type 4 tissue inhibitor of metalloproteinases (TIMP-4), and collagen I and III by immunohistochemical staining or Western blotting. RESULTS: Femoral AVF resulted in a sixfold increase in blood flow in the fistula iliac vein and a gradual, but significant, increase in the thickness of the intima and media and marked up-regulation of MMP-2 and MMP-9, down-regulation of TIMP-4, as well as degradation of collagens I and III. The collagen I/III ratio was significantly higher in the 14-day fistula group (1.44 +/- 0.32) than in the sham group (0.82 +/- 0.15) and was even higher in the 28-day fistula group (1.76 +/- 0.21). CONCLUSION: The present results confirmed our hypothesis that a high blood flow rate in the fistula vein affects the expression of MMPs and TIMP-4, resulting in the remodeling or maturation of the AVF. Remodeling is associated with degradation of collagen, with an increase in the collagen I/III ratio.     

Plasma concentration of tissue inhibitor of matrix metalloproteinase 1 in patients with colorectal carcinoma.

BACKGROUND: The expression of tissue inhibitor of matrix metalloproteinase (TIMP) 1 in tumour tissue from patients with colorectal carcinoma has been reported to be related to disease progression. However, the clinical significance of plasma TIMP-1 has not been fully elucidated. METHODS: The plasma level of TIMP-1 protein was determined by enzyme-linked immunosorbent assay in samples from 54 patients who underwent resection of the primary tumour. RESULTS: Plasma TIMP-1 levels were associated significantly with depth of invasion and metastasis to lymph nodes and liver. Circulating TIMP-1 levels were significantly higher in patients with serosal invasion, liver metastases and Dukes' stage C tumours. Using a cut-off value of 160 ng/ml, serosal invasion and Dukes' C stage could be predicted with an accuracy of 68.5 per cent. With a cut-off value of 170 ng/ml, metastasis to the lymph node and liver could be predicted with an accuracy of 66.7 and 70.4 per cent respectively. These values were greater than those for carcinoembryonic antigen and CA19-9. CONCLUSION: These data suggest that the plasma concentration of TIMP-1 correlates with both invasion and metastasis in patients with colorectal carcinoma.     

基质金属蛋白酶抑制剂对胶质瘤细胞和胶质瘤干细胞体外侵袭抑制作用的比较

目的 观察基质金属蛋白酶(MMP)抑制剂对常规贴壁培养的人脑胶质瘤细胞和胶质瘤干细胞侵袭能力的影响及两者间的差异.方法 应用一种三维胶原凝胶侵袭模型,将常规贴壁培养的胶质瘤细胞与无血清、悬浮细胞球条件下培养的胶质瘤干细胞(1. 0×104～1.5×104个/样本)分别接种于该模型中,加入不同浓度的MMP抑制剂GM6001(0、25、50、75、100 μmol/L)培养4 d,通过观察各组细胞侵袭距离及其差异,判断该抑制剂对两种细胞侵袭能力的影响及差异.结果 两组细胞对GM6001的抑制作用表现出不同程度的剂量依赖性,75μmol/L GM6001对常规培养的胶质瘤细胞侵袭抑制最明显,而25 μmol/L GM6001对胶质瘤干细胞的侵袭抑制最显著.结论 MMP抑制剂在体外对胶质瘤细胞具有侵袭抑制作用,胶质瘤干细胞显示出对MMP抑制剂更高的敏感性.     

The effects of a broad-spectrum matrix metalloproteinase inhibitor on characteristics of wound healing.

This study investigates the effects of a broad-spectrum matrix metalloproteinase inhibitor (MMP-i) on the rate of closure, hydroxyproline deposition, and macrophage infiltration in healing wounds. Full-thickness excisional wounds were created on the dorsal surface of hairless mice. Two experimental groups were used to measure rates of wound closure: (a) MMP-i administration (0.03, 0.3, 3.0, and 30 microg/mL) on days 0-1 postwounding (inflammatory phase) and (b) MMP-i administration (0.03, 0.3, 3.0, and 30 microg/mL) on days 6-8 postwounding (proliferative phase). Additionally, hydroxyproline deposition and percent macrophage infiltration were measured in skin wound margins on days 2, 8, and 16 postwounding. MMP-i administration at concentrations of 0.03, 0.3, and 3.0 microg/mL on days 0-1 postwounding significantly (p <.05) increased the rate of wound closure. No significant effect on the rate of wound closure was observed with MMP-i administration on days 6-8 postwounding. Hydroxyproline deposition was significantly (p <.05) increased on day 8 postwounding, and the percent macrophage infiltration was significantly (p <.05) decreased on day 2 postwounding by MMP-i administration on days 0-1 postwounding. These experiments demonstrate that MMP-i administration during the inflammatory phase significantly affects several characteristics of wound healing. We postulate that these effects may be attributed to decreased degradation of ECM components, increased concentrations of endogenous growth factors, and a shortened inflammatory phase.     

Effect of a matrix metalloproteinase activity and TNF-alpha converting enzyme inhibitor on intra-abdominal adhesions

BACKGROUND: Formation of intra-abdominal adhesions depends, in part, on the activity of serine proteinases. Matrix metalloproteinases (MMP) are required for epithelialization of skin wounds but their involvement in mesothelialization of peritoneal wounds and in adhesion pathogenesis is not known. Early tumor necrosis factor-alpha (TNF-alpha) levels have been proposed to reflect propensity to adhesion formation. OBJECTIVE: The impact of MMP activity and secreted TNF-alpha on peritoneal adhesion formation and healing was investigated through systemic administration of the synthetic broad-spectrum MMP and TNF-alpha-converting enzyme (TACE) inhibitor GM 6001. METHODS: Female Sprague-Dawley rats of 4-6 weeks of age were injected subcutaneously daily with GM 6001 100 mg/kg (n = 12) or vehicle (n = 10) starting two days before surgery. In each rat, two standardized peritoneal wounds, 20 mm x 5 mm, were made. One peritoneal wound was sutured whereas the contralateral wound healed by secondary intention. Adhesion formation and peritoneal healing, cell proliferation, and hydroxyproline concentrations were evaluated on postoperative day 7. RESULTS: Total serum TNF-alpha levels increased in vehicle-treated rats (p = 0.019) while GM 6001 treatment effectively prevented the rise in the postoperative phase (p < 0.001). No significant differences were observed in the extent of adhesion formation (p = 0.67) between control (65.0%) and GM 6001-treated (61.5%) animals, or peritoneal wound healing or cell proliferation. Hydroxyproline levels increased in the wounds (p = 0.014) but were not different between the two groups (p = 0.14). CONCLUSIONS: Lack of a striking effect of the MMP and TACE antagonist GM 6001 on postoperative adhesions suggests that MMP activity and TNF-alpha might not be major adhesiogenic factors.     

Moderation of iodoacetate-induced experimental osteoarthritis in rats by matrix metalloproteinase inhibitors

OBJECTIVE: To determine the effect of matrix metalloproteinase (MMP) inhibitors in mono-iodoacetate-induced arthritis in rats. DESIGN: The ability of compounds to inhibit MMPs in vitro was assessed kinetically using a quenched fluorescent substrate. Rats were injected with iodoacetate intraarticularly in one knee joint and damage to the tibial plateau was evaluated from digitized images captured using an image analyser and by histology. Collagenase and gelatinase activity in cartilage from iodoacetate injected knees were evaluated using(3)H-rat type I collagen and gelatin zymography, respectively. RESULTS: Collagenase and gelatinase activity significantly increased in the knee cartilage of rats injected with iodoacetate with peak activity by day 7. Three MMP inhibitors were examined for their efficacy in the rat iodoacetate-induced arthritis model. Significant (P< 0.05) inhibition of cartilage damage was observed in animals treated orally with 35 mg/kg b.i.d. of the three different MMP inhibitors. Inhibition of cartilage damage by the MMP inhibitors ranged from 36-42%. CONCLUSION: MMP inhibitors are partially protective against cartilage and subchondral bone damage induced by iodoacetate. These results support an important role for MMPs in mediating the joint damage in this model of arthritis.     

Effect of matrix metalloproteinase inhibition on colonic anastomotic healing in rats

Wound strength depends on the balance between collagen synthesis and degradation; however, the role of collagen breakdown in wound healing is still not well understood. We investigated the role of matrix metalloproteinases in wound healing by using BE16627B, a matrix metalloproteinase inhibitor. Identical surgical procedures consisting of a colonic anastomosis (single-layer, inverted) and implantation of an osmotic pump in the back were performed in male Sprague-Dawley rats weighing 270 to 290 grams. The animals were randomly assigned to receive either BE16627B (n = 10) dissolved in dimethylsulfoxide and diluted with ethylene glycol at a dosage of 2.4 mg/rat/day for 3 days or the vehicle solution alone (n = 11). The solutions were administered through the surgically implanted osmotic pumps. The animals were killed 4 days after surgery, and the colonic bursting pressure (mm Hg) and hydroxyproline concentration (μg/mg wet tissue, index of collagen) were measured. The administration of BE16627B enhanced colonic anastomotic healing, as measured by the increase in the colonic bursting pressure (160 ±12 vs. 125 ±7 mm Hg; P <0.05) and the increase in the soluble fraction of collagen (0.27 ± 0.01 vs. 0.21 ± 0.01 μg/mg wet tissue; P <0.01) in the anastomosis. Histologic examination of the tissue revealed that the use of BE 1662 7B resulted in the preservation of the multilayered colonic structure and increased the network of collagen between both ends of the colon in the thickening submucosal layer. These findings demonstrate that the inhibition of matrix metalloproteinase activity influences colonic anastomotic healing, indicating a potential mechanism for enhancing anastomotic healing. Supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science. Presented at the Forty-First Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 21–24, 2000.     

大豆苷元干预Hedgehog信号通路调控去卵巢骨质大鼠基质金属蛋白酶代谢

目的 探究大豆苷元对骨质疏松（osteoporosis,OP）模型大鼠Hedgehog信号通路的调控作用,分析大豆苷元对OP大鼠基质金属蛋白酶代谢的影响。方法 随机将60只雌性SPF级Wistar大鼠分为假手术组、模型组、大豆苷元低、中、高剂量治疗组5组,每组12只。除假手术组,其他4组均采用去卵巢法建立OP模型。造模成功后开始干预治疗,假手术组、模型组等剂量生理盐水灌胃,其他给予大豆苷元低、中、高剂量治疗,连续干预12周。酶联免疫吸附法测定各组大鼠血清雌激素（E2）、骨钙素（BGP）、血清碱性磷酸酶（ALP）含量水平;免疫组化法检测各组大鼠股骨组织中基质金属蛋白酶组织抑制剂-1（TIMP-1）和基质金属蛋白酶-7（MMP-7）免疫蛋白的表达情况;TUNEL染色法检测各组骨细胞凋亡情况;RT-PCR法和WB法检测各组骨组织中Shh、PTC1、Gli1 mRNA及蛋白表达水平。结果 大豆苷元能显著提高OP大鼠大鼠E2、TIMP-1水平,降低细胞凋亡及 BGP、ALP、MMP-7水平;显著改善股骨组织中Shh、PTC1、Gli1 mRNA及蛋白表达水平（P＜0.05）,且大豆苷元不同组具有剂量依赖性（P＜0.01）。结论 大豆苷元可有效调控OP模型大鼠基质金属蛋白酶代谢水平,这可能与大豆苷元能够有效调节Hedgehog信号通路表达相关。     

基质金属蛋白酶9在多器官功能障碍综合征大鼠肾组织的表达

炎性介质的大量释放导致内皮细胞损伤是引起多器官功能障碍综合征(MODS)的基础.有关器官内皮细胞激活和损伤在MODS病理过程中的作用研究较多~([1]),而细胞外基质在MODS中的变化及与其的关系目前还未检索到相关报道.因此,我们选择了降解细胞外基质主要成分Ⅳ型胶原的基质金属蛋白酶9(MMP-9)作为观察指标,并与血清MMP-9比较,探讨细胞外基质的变化在MODS肾损伤中的作用.     

ONO-4817, a novel matrix metalloproteinase inhibitor, attenuates allograft vasculopathy in a rat cardiac transplant.

BACKGROUND: Cardiac allograft vasculopathy (CAV), a disorder characterized by rapid development and progression of obliterative vasculopathy in the transplanted heart, continues to be a major cause of graft failure in long-surviving human transplants. The mechanisms and histopathologic processes of CAV remain unknown. Previous animal studies have shown that inhibition of matrix metalloproteinase (MMP) prevents migration and proliferation of smooth muscle cells in CAV. In this study, we hypothesized that MMPs may be expressed in and may play an important role in CAV. METHODS: An F344-to-WKAH rat heterotopic heart transplantation model was used. Tacrolimus was administered intramuscularly 14 days after transplantation to prevent acute rejection and to allow the development of CAV. We divided the animals into 2 groups according to post-operative treatment: an ONO group received an MMP inhibitor (ONO-4817) daily by oral gavage for 14 days after transplantation (n = 6), and a control (n = 6) group received no treatment. Grafts were harvested 60 days after treatment. RESULTS: Immunohistochemical staining revealed that MMP-2 and tissue inhibitors of metalloproteinase-2 (TIMP-2) were expressed more strongly in the neointima and media of the control CAV animals than in the ONO-CAV animals. The animals given ONO-4817 exhibited a significant decrease in the percentage of affected vessels, in the percentage of intimal proliferation, in the intima-to-media ratio, and in the expression of MMP-2 and TIMP-2. CONCLUSION: These results suggest that MMP-2 and TIMP-2 play an important role in the development of CAV and that the use of an MMP inhibitor (ONO-4817) may prevent neointimal proliferation in patients with CAV.     

Suppression of experimental abdominal aortic aneurysms by systemic treatment with a hydroxamate-based matrix metalloproteinase inhibitor (RS 132908)

BACKGROUND: Abdominal aortic aneurysms (AAAs) are associated with chronic inflammation, disruption of medial elastin, and increased local production of elastolytic matrix metalloproteinases (MMPs). The purpose of this study was to investigate how treatment with a hydroxamate-based MMP antagonist (RS 132908) might affect the development of experimental AAAs. METHODS: Male Wistar rats underwent intraluminal perfusion of the abdominal aorta with 50 units of porcine pancreatic elastase followed by treatment for 14 days with RS 132908 (100 mg/kg/day subcutaneously; n = 8) or with vehicle alone (n = 6). The external aortic diameter (AD) was measured in millimeters before elastase perfusion and at death, with AAA defined as an increase in AD (DeltaAD) of at least 100%. Aortic wall elastin and collagen concentrations were measured with assays for desmosine and hydroxyproline, and fixed aortic tissues were examined by light microscopy. RESULTS: AAAs developed in all vehicle-treated rats, with a mean AD (+/- SE) that increased from 1.60 +/- 0.03 mm before perfusion to 5.98 +/- 1.02 mm on day 14 (DeltaAD = 276.4 +/- 67.7%). AAAs developed in only five of eight animals (62.5%) after MMP inhibition, with a mean AD that increased from 1.56 +/- 0.05 mm to 3.59 +/- 0.34 mm (DeltaAD = 128.1 +/- 18.7%; P <.05, vs vehicle). The overall inhibition of aortic dilatation attributable to RS 132908 was 53.6 +/- 6.8%. Aortic wall desmosine fell by 85.4% in the vehicle-treated rats (1210.6 +/- 87.8 pmol/sample to 176.7 +/- 33.4 pmol/sample; P <.05) but only by 65.6% in the animals treated with RS 312908 (416.2 +/- 120.5 pmol/sample). In contrast, hydroxyproline was not significantly affected by either elastase perfusion or drug treatment. Microscopic examination revealed the preservation of pericellular elastin and a greater degree of fibrocollagenous wall thickening after MMP inhibition, with no detectable difference in the extent of inflammation. CONCLUSIONS: Systemic MMP inhibition suppresses aneurysmal dilatation in the elastase-induced rodent model of AAA. Consistent with its direct inhibitory effect on various MMPs, RS 132908 promotes the preservation of aortic elastin and appears to enhance a profibrotic response within the aortic wall. Hydroxamate-based MMP antagonists may therefore be useful in the development of pharmacologic approaches to the suppression of AAAs.     

心室重塑中基质金属蛋白酶和组织抑制酶的表达

目的 观察大鼠心肌梗死后基质金属蛋白酶-2，9(MMP-2，9)和组织金属蛋白酶抑制剂-1(TIMP-1)的变化规律。方法 结扎SD大鼠冠状动脉前降支建立心肌梗死模型。分为对照组(n=20)、心肌梗死组(Ⅰ组，n=48)，酶谱法测定心肌梗死后MMP-2，9活性蛋白的表达规律，Western blotting进一步确定所消化条带酶的属性。结果正常心肌中无活性MMP-9的存在。MMP-2蛋白水平在心肌梗死后第1、2周活性增强、表达增加，MMP-9第1、2、4周活性增强、表达增加，TIMP-1蛋白含量减少。结论 心肌梗死后心肌组织内MMP-2，9的活性增高和蛋白含量增加，TIMP-1蛋白含量减少，是心室重塑机制重要组成部分。MM-9在心肌梗死后心室重塑过程中可能具有特殊的地位。