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Neural Regeneration Research 2012年第17期7卷 1325-1330页

作者： Yuqiang Song Hongli Zou Guofeng Wang Hongxia Yang Zhaohong Xie Jianzhong Bi Department of Neurology the Affiliated Hospital of Medical College Qingdao University Qingdao 266003 Shandong Province China Qingdao Central Hospital Qingdao 266042 Shandong Province China Qingdao No. 9 People＇s Hospital Qingdao 266003 Shandong Province China The Second Hospital of Shandong University Jinan 255000 Shandong Province China

Activity of matrix metalloproteinase-9 increases following cerebral ischemia/reperfusion, and is associated with cerebral microvascular permeability, blood-brain barrier destruction, inflammatory cell infiltration and brain edema. matrix metalloproteinase-9 also likely participates in thrombolysis. A rat model of middle cerebral artery infarction was established by injecting autologous blood clots into the internal carotid artery. At 3 hours following model induction, urokinase was injected into the caudal vein. Decreased neurological severity score, reduced infarct volume, and increased expression of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 were observed in the cerebral cortex 24 hours after urokinase thrombolysis. These results suggest that urokinase can suppress damage in the acute-early stage of cerebral infarction.

关键词： cerebral infarction urokinase thrombolysis matrix metalloproteinase-9 tissue inhibitor ofmetalloproteinase-1 neural regeneration

matrix metalloproteinase-9 was involved in the immuno-modulatory defect of mesenchymal stem cell from chronic myeloid leukemia patients

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Chinese Medical Journal 2011年第16期124卷 2423-2430页

作者： ZHU Xi-shan SHI Wei AN Guang-yu ZHANG Hong-mei SONG Yu-guang LI You-bin Institute of Internal Oncology Center of Tumor Research andTherapy Beijing Shijitan Hospital Capital Medical University (theNinth Medical College of Peking University) Beijing 100038China

Background Overwhelming evidences on chronic myeloid leukemia （CML） indicate that patients harbor quiescent CML stem cells that are responsible for blast crisis. While the hematopoietic stem cell （HSC） origin of CML was first suggested over 30 years ago, recently CML-initiating cells beyond HSCs are also being investigated. Methods We have previously isolated fetal liver kinase-l-positive （Flkl＋） cells carrying the BCR/ABL fusion gene from the bone marrow of Ph＋ patients with hemangioblast property. In this study, we isolated CML patient-derived FIk1＋CD31-CD34- mesenchymal stem cells （MSCs） and detected their biological characteristics and immunological regulation using fluorescence in situ hybridization （FISH） analysis, fluorescence activated cell sorting （FACS）, enzyme-linked immunoadsorbent assay, mixed lymphocyte reaction assays; then we compared these characters with those of the healthy donors. Results CML patient-derived FIk1＋CD31-CD34- MSCs had normal morphology, phenotype and karyotype while appeared impaired in immuno-modulatory function. The capacity of patient FIk1＋CD31-CD34- MSCs to inhibit T lymphocyte activation and proliferation was impaired in vitro. Conclusions CML patient-derived MSCs have impaired immuno-modulatory functions, suggesting that the dysregulation of hematopoiesis and immune response may originate from MSCs rather than hematopoietic stem cells （HSCs）. MSCs might be a potential target for developing efficacious treatment for CML.

关键词： chronic myeloid leukemia mesenchymal stem cell immune regulation matrix metalloproteinase-9

matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2008年第5期3卷 505-508页

作者： Lifang Lei Xiaohong Zi Qiuyun Tu Department of Neurology Third Xiangya Hospital Central South University Changsha 410083 Hunan Province China

BACKGROUND： The integrity of the blood brain barrier （BBB） plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 （MMP-9） is closely related to cerebral ischemia/reperfusion injury OBJECTIVE： This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability. DESIGN, TIME AND SETTING： This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006. MATERIALS： Ninety healthy male SD rats, aged 3-4 months, weighing 200-280 g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody （Boster, Wuhan, China） and Evans blue （Sigma, USA） were also used. METHODS： All rats were randomly divided into 9 groups with 10 rats in each group： normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3, 6, 12 hours, 1, 2, 4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled. MAIN OUTCOME MEASURES： BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method. RESULTS： All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and th

关键词： ischemia/reperfusion injury matrix metalloproteinase-9 blood brain barrier

Regulation of matrix metalloproteinase-2 and matrix metalloproteinase-9 in Abdominal Aortic Aneurysm

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Cardiology Discovery 2023年第3期3卷 212-220页

作者： Shuo Wang Dan Liu Xiaolin Zhang Xiaoxiang Tian Department of Cardiology and Cardiovascular Research Institute General Hospital of Northern Theater CommandShenyang 110016China Department of Cardiology Shengjing Hospital of China Medical UniversityShenyang 110022China.

Abdominal aortic aneurysm (AAA) is a degenerative disease characterized by destruction and progressive expansion of the abdominal aortic wall. An AAA is typically defined as an enlargement of the abdominal aorta with diameter ≥3 cm or ≥50% greater than the suprarenal diameter. The pathological changes associated with AAA include inflammatory cell infiltration, extracellular matrix (ECM) destruction and remodeling, and vascular smooth muscle cell loss. The matrix metalloproteinase (MMP) family of proteins plays an important role in initiation and progression of AAA. Since understanding the regulation of MMP-2 and MMP-9 in AAA is essential for treatment of AAA, this review summarized the regulatory mechanisms of MMPs to provide a reference for exploring novel therapeutic approaches.

关键词： Aortic aneurysm abdominal aortic matrix metalloproteinase-2 matrix metalloproteinase-9

Rhubarb Antagonizes matrix metalloproteinase-9-induced Vascular Endothelial Permeability

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Chinese Medical Journal 2016年第14期129卷 1737-1743页

作者： Yun-Liang Cui Sheng Zhang Zhao-Tao Tian Zhao-Fen Lin De-Chang Chen Department of Critical Care Medicine Jinan Military General Hospital Jinan Shandong 250031 China Department'of Emergency Medicine Changzheng Hospital Second Militaiy Medical University-Shanghai 200003 China

Background： Intact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 （MMP9）-induced vascular endothelial （VE） permeability. Methods： Rhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance （NMR）, carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell （HUVEC） monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers. Results： A total of 21 rhubarb monomers were extracted and identifed. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer （emodin, 3,8-dihydroxy- 1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-（4-hydroxyl-O-cinnamoyl）-β-D-glucose, daucosterol linoleate, and rhein） or a combination of all five monomers （1μmol/L for each monomer）. Mechanistically, the five-monomer mixture at 1 μmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture. Conclusions： The rhubarb mixture ofemodin, 3,8-dihydroxy-l-methyl-anthraquinone-2-carboxylic ac

关键词： matrix metalloproteinase-9 Monomer Peneability Rhubarb Vascular Endothelial-cadherin: Vascular Endothelial Cell

Duodenal-jejunal bypass surgery on type 2 diabetic rats reduces the expression of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in the thoracic aorta

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Chinese Medical Journal 2014年第13期127卷 2423-2428页

作者： Maimaitiyusufu Wubulikasimu Han Haifeng Yan Zhibo Zhang Xiang Liu Shaozhuang Zhang Guangyong Kasimu Aimaiti Hu Sanyuan Department of General Surgery Qilu Hospital of ShandongUniversity Jinan Shandong 250012 China

Background Bariatric surgery offers a productive resolution of type 2 diabetes mellitus （T2DM）.The development of T2DM vasculopathy is due to chronic inflammation,which increases matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of matrix metalloproteinase-1 （TIMP-1） *** study sought to examine MMP-9 and TIMP-1 expression in the thoracic aorta after duodenal-jejunal bypass （DJB） surgery on a T2DM rat model induced by a high-fat diet and low dose streptozotocin （STZ）.Methods Twenty-one T2DM Wistar rats induced by high-fat diet and low dose STZ were randomly divided into DJB and sham duodenal-jejunal bypass （S-DJB） *** Wistar rats were fed a normal diet as a *** of gastrointestinal function post-operation and resumption of a normal diet completed the *** weight,blood glucose,blood lipid levels,and MMP-9 and TIMP-1 expression levels in aortic endothelial cells were measured *** DJB rats showed significant weight loss 2 weeks post-operation compared with S-DJB *** surgery,DJB rats showed significant improvement and steady glycemic control with improved insulin sensitivity and glucose *** also exhibited improved lipid metabolism with a decrease in fasting free fatty acids （FFAs） and triglycerides （all P ＜0.05）.Immunohistochemistry showed decreased MMP-9 and TIMP-1 expression 12 weeks after surgery （P ＜ 0.01）.Conclusions DJB surgery on an induced T2DM rat model improves blood glucose levels and lipids,following a high-fat diet and low dose STZ *** addition,DJB decreased MMP-9 and TIMP-1 expression in vascular endothelial cells,which may play an important role in delaying the development of T2DM vascular disease.

关键词： type 2 diabetes mellitus vasculopathy matrix metalloproteinase-9 tissue inhibitor of matrix metalloproteinase-1 duodenal-jejunal bypass

High matrix metalloproteinase-9 expression induces angiogenesis and basement membrane degradation in stroke-prone spontaneously hypertensive rats after cerebral infarction

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Neural Regeneration Research 2014年第11期9卷 1154-1162页

作者： Huilian Hou Guanjun Zhang Hongyan Wang Huilin Gong Chunbao Wang Xuebin Zhang Department of Pathology the First Affiliated Hospital of Medical School of Xi’an Jiaotong University

Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke- prone spontaneously hypertensive rats by intragastric administration of high-sodium water （1.3% NaC1） for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone sponta- neously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregula- tion is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodi- um water-induced focal cerebral infarction.

关键词： nerve regeneration cerebral infarction matrix metalloproteinase-9 collagen IV microvessel density angiogenesis basement membrane degradation high sodium stroke-pronespontaneously hypertensive China Medical Board Project neural regeneration

Salvianolic Acid B Down-regulates matrix metalloproteinase-9 Activity and Expression in Tumor Necrosis Factor-α-induced Human Coronary Artery Endothelial Cells

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Chinese Medical Journal 2015年第19期128卷 2658-2663页

作者： Le Ma Yun-Qian Guan Zhong-Dong Du Department of Pediatrics Beijing Children's HospitalCapital Medical UniversityBeijing 100045China Cell Therapy Center Beijing Institute of GeriatricsXuanwu Hospital of Capital Medical UniversityBeijing 100053China

Background：Salvianolic acid B （Sal B） is a bioactive water-soluble compound of Salviae miltiorrhizae,a traditional herbal medicine that has been used clinically tor the treatment of cardiovascular *** study sought to evaluate the effect of Sal B on matrix metalloproteinase-9 （MMP-9） and on the underlying mechanisms in tumor necrosis factor-α （TNF-α）-activated human coronary artery endothelial cells （HCAECs）,a cell model of Kawasaki ***：HCAECs were pretreated with 1 l0 μmol/L of Sal B,and then stimulated by TNF-α at different time *** protein expression and activity of MMP-9 were determined by Western blot assay and gelatin zymogram assay,*** factor-κB （NF-κB） activation was detected with immunofluorescence,electrophoretic mobility shift assay,and Western blot *** expression levels of mitogen-activated protein kinase （c-Jun N-terminal kinase [JNK],extra-cellular signal-regulated kinase [ERK],and p38） were determined by Western blot ***：After HCAECs were exposed to TNF-α,1-10 μtmol/L Sal B significantly inhibited TNF-α-induced MMP-9 expression and ***,Sal B significantly decreased IκBα phosphorylation and p65 nuclear translocation in HCAECs stimulated with TNF-α for 30 *** addition,Sal B decreased the phosphorylation of JNK and ERK1/2 proteins in cells treated with TNF-α for 10 ***：The data suggested that Sal B suppressed TNF-α-induced MMP-9 expression and activity by blocking the activation of NF-κB,JNK,and ERK1/2 signaling pathways.

关键词： Endothelial Cell Injury Kawasaki Disease Mitogen-activated Protein Kinase matrix metalloproteinase-9 Nuclear factor-κB Salvianolic Acid B

Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue

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Neural Regeneration Research 2013年第34期8卷 3216-3224页

作者： Desheng Zhou Mei Li Hua Hu Yao Chen Yang Yang Jie Zhong Lijuan Liu Department of Neurology First Hospital of Hunan University of Chinese Medicine Department of Internal Medicine Pingxiang Hospital of Traditional Chinese Medicine Department of Neurology People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine

Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3：2：6：2：3：3：3：3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.

关键词： neural regeneration traditional Chinese medicine Huoxue Rongluo Tablet cerebral infarction neuroprotection matrix metalloproteinase-9 buflomedil pyridoxal phosphate grants-supportedpaper neuroregeneration

Picroside Ⅱ down-regulates matrix metalloproteinase-9 expression following cerebral ischemia/reperfusion injury in rats

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Neural Regeneration Research 2010年第18期5卷 1403-1407页

作者： Xiang Li Xinying Xu Zhen Li Yunliang Guo Qin Li Xiaodan Li Zhen Zhou Department of Ultrasound Affiliated Hospital of Qingdao University Medical College Qingdao 266003 Shandong Province China Institute of Cerebrovascular Disease Qingdao University Medical College Qingdao 266003 Shandong Province China Yuhuangding Hospital Qingdao University Medical College Qingdao 266003 Shandong Province China Experimental Center of Surgery Qingdao University Medical College Qingdao 266003 Shandong Province China

Studies have shown that Picroside Ⅱ attenuates inflammatory reactions following brain ischemia through the inhibition of the TLR-4-NF-KB signal transduction pathway, and ameliorates cerebral edema through the reduction of aquaporin-4 expression. matrix metalloproteinase-9 （MMP-9）, located downstream of the TLR-4-NF-KB signal transduction pathway, can degrade the neurovascular matrix, damage the blood-brain barrier to induce cerebral edema, and directly result in neuronal apoptosis and brain injury, Therefore, the present study further observed MMP-9 expression in the brain tissues of rats with cerebral ischemia/reperfusion injury following Picroside Ⅱ treatment. Results demonstrated that Picroside Ⅱ significantly reduced MMP-9 expression in ischemic brain tissues, as well as neuronal apoptosis and brain infarct volume, suggesting Picroside Ⅱ exhibits neuroprotection by down-regulating MMP-9 expression and inhibiting cell apoptosis.

关键词： Picroside Ⅱ cerebral ischemia/reperfusion injury apoptosis matrix metalloproteinase-9 rats neural regeneration