scholarly journals Decreased uterine vascularization and uterine arterial expansive remodeling with reduced matrix metalloproteinase-2 and -9 in hypertensive pregnancy

2020 ◽  
Vol 318 (1) ◽  
pp. H165-H180 ◽  
Author(s):  
Chen Lin ◽  
Hong He ◽  
Ning Cui ◽  
Zongli Ren ◽  
Minglin Zhu ◽  
...  
Keyword(s):  
Proteolytic Enzymes ◽  
Gelatin Zymography ◽  
Collagen Iv ◽  
Intraluminal Pressure ◽  
Matrix Metalloproteinase 2 ◽  
Trophoblast Invasion ◽  
Related Disorder ◽  
Uterine Arteries ◽  
Ecm Proteins ◽  
Placental Ischemia

Normal pregnancy involves extensive remodeling of uterine and spiral arteries and matrix metalloproteinases (MMPs)-mediated proteolysis of extracellular matrix (ECM). Preeclampsia is characterized by hypertension in pregnancy (HTN-Preg) and intrauterine growth restriction (IUGR) with unclear mechanisms. Initial faulty placentation and reduced uterine perfusion pressure (RUPP) could release cytoactive factors and trigger an incessant cycle of suppressed trophoblast invasion of spiral arteries, further RUPP, and progressive placental ischemia leading to HTN-Preg and IUGR; however, the extent and depth of uterine vascularization and the proteolytic enzymes and ECM proteins involved are unclear. We hypothesized that HTN-Preg involves decreased uterine vascularization and arterial remodeling by MMPs and accumulation of ECM collagen. Blood pressure (BP) and fetal parameters were measured in normal Preg rats and RUPP rat model, and the uteri were assessed for vascularity, MMP levels, and collagen deposition. On gestational day 19, BP was higher, and the uterus weight, litter size, and pup weight were reduced in RUPP vs. Preg rats. Histology of uterine tissue sections showed reduced number (5.75 ± 0.95 vs. 11.50 ± 0.87) and size (0.05 ± 0.01 vs. 0.12 ± 0.02 mm2) of uterine spiral arterioles in RUPP vs. Preg rats. Immunohistochemistry showed localization of endothelial cell marker cluster of differentiation 31 (CD31) and smooth muscle marker α-actin in uterine arteriolar wall and confirmed decreased number/size of uterine arterioles in RUPP rats. The cytotrophoblast marker cytokeratin-7 showed less staining and invasion of spiral arteries in the deep decidua of RUPP vs. Preg rats. Uterine arteries showed less expansion in response to increases in intraluminal pressure in RUPP vs. Preg rats. Western blot analysis, gelatin zymography, and immunohistochemistry showed decreases in MMP-2 and MMP-9 and increases in the MMP substrate collagen-IV in uterus and uterine arteries of RUPP vs. those in Preg rats. The results suggest decreased number, size and expansiveness of spiral and uterine arteries with decreased MMP-2 and MMP-9 and increased collagen-IV in HTN-Preg. Decreased uterine vascularization and uterine arterial expansive remodeling by MMPs could be contributing mechanisms to uteroplacental ischemia in HTN-Preg and preeclampsia. NEW & NOTEWORTHY Preeclampsia is a pregnancy-related disorder in which initial inadequate placentation and RUPP cause the release of cytoactive factors and trigger a ceaseless cycle of suppressed trophoblast invasion of spiral arteries, further RUPP, and progressive placental ischemia leading to HTN-Preg and IUGR; however, the extent/depth of uterine vascularization and the driving proteolytic enzymes and ECM proteins are unclear. This study shows decreased number, size, and expansiveness of uterine spiral arteries, with decreased MMP-2 and MMP-9 and increased collagen-IV in HTN-Preg rats. The decreased uterine vascularization and uterine arterial expansive remodeling by MMPs could contribute to progressive uteroplacental ischemia in HTN-Preg and preeclampsia.

scholarly journals Renal Expression of Fibrotic Matrix Proteins and of Transforming Growth Factor-β (TGF-β) Isoforms in TGF-β Transgenic Mice

1999 ◽  
Vol 10 (2) ◽  
pp. 271-280
Author(s):  
MIKLOS M. MOZES ◽  
ERWIN P. BÖTTINGER ◽  
TERRY A. JACOT ◽  
JEFFREY B. KOPP
Keyword(s):  
Growth Factor ◽  
Transgenic Mice ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Gelatin Zymography ◽  
Collagen Iv ◽  
Collagen I ◽  
Matrix Metalloproteinase 2 ◽  
Northern Analysis ◽  
Tgf Β1

Abstract. Renal pathology in mice that are transgenic for the murine albumin enhancer/promoter linked to a full-length porcine transforming growth factor-β1 (TGF-β1) gene has been described previously. In these mice, transgene expression is limited to the liver and the plasma level of TGF-β is increased. The earliest renal pathologic change is glomerulosclerosis, at 3 wk of age, and this is followed by tubulointerstitial fibrosis. In this study, it was hypothesized that circulating TGF-β1 increases renal extracellular matrix accumulation and activates local TGF-β gene expression. Immunostaining at 5 wk revealed increased amounts of collagen I and III within the mesangium, glomerular capillary loops, and interstitium, while the amount of collagen IV was normal. Similarly, Northern analysis showed increased expression of mRNA encoding collagen I and III, as well as biglycan and decorin, while the expression of collagen IV was unchanged. These changes began as early as 1 wk of age, a time before the appearance of glomerulosclerosis. To evaluate matrix degradation, collagenase IV activity was evaluated by gelatin zymography and an increase in matrix metalloproteinase-2 was found. Finally, the production of tissue inhibitors of metalloproteinase was evaluated. Tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA was increased 18-fold, while TIMP-2 and TIMP-3 were unchanged. In 2-wk-old transgenic kidney, local expression of TGF-β1, β2, and β3 protein was similar to wild-type mice. In 5-wk-old transgenic mice, TGF-β1 and β2 protein was present in increased amounts within glomeruli, and renal TGF-β1 mRNA was increased threefold. It is concluded that elevated levels of circulating TGF-β1 may act on the kidney to increase matrix protein production and decrease matrix remodeling. Only after glomerulosclerosis is established does local glomerular overproduction of TGF-β become manifest.

scholarly journals Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Binbin Zheng ◽  
Hongbo Yang ◽  
Jianan Zhang ◽  
Xueli Wang ◽  
Hao Sun ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Gelatin Zymography ◽  
Neutrophil Infiltration ◽  
Negative Regulator ◽  
Matrix Metalloproteinase 2 ◽  
Cytokine Signaling

Acute lung injury (ALI) is one of the fatal symptoms of sepsis. However, there were no effective clinical treatments. TF accumulation-induced fibrin deposit formations and coagulation abnormalities in pulmonary vessels contribute to the lethality of ALI. Suppressor of cytokine signaling 3 (SOCS3) acts as an endogenous negative regulator of the TLR4/TF pathway. We hypothesized that inducing SOCS3 expression using lidocaine to suppress the TLR4/TF pathway may alleviate ALI. Hematoxylin and eosin (H&E), B-mode ultrasound, and flow cytometry were used to measure the pathological damage of mice. Gelatin zymography was used to measure matrix metalloproteinase-2/9 (MMP-2/9) activities. Western blot was used to assay the expression of protein levels. Here, we show that lidocaine could increase the survival rate of ALI mice and ameliorate the lung injury of ALI mice including reducing the edema, neutrophil infiltration, and pulmonary thrombosis formation and increasing blood flow velocity. Moreover, in vitro and in vivo, lidocaine could increase the expression of p-AMPK and SOCS3 and subsequently decrease the expression of p-ASK1, p-p38, TF, and the activity of MMP-2/9. Taken together, our study demonstrated that lidocaine could inhibit the TLR4/ASK1/TF pathway to alleviate ALI via activating AMPK-SOCS3 axis.

scholarly journals Preeclampsia: From Inflammation to Immunoregulation

2018 ◽  
Vol 11 ◽  
pp. 1179545X1775232 ◽  
Author(s):  
Denise C Cornelius
Keyword(s):  
T Cells ◽  
Rat Model ◽  
The United States ◽  
Therapeutic Interventions ◽  
Trophoblast Invasion ◽  
Positive Effects ◽  
Immune Balance ◽  
Uterine Perfusion ◽  
Immune Imbalance ◽  
Placental Ischemia

Preeclampsia (PE) affects 5% to 7% of pregnant women each year worldwide, accounts for up to 18% of maternal deaths in the United States each year, and is the number 1 cause of premature births. Preeclampsia is associated with hypertension after the 20th week of gestation with or without proteinuria, in conjunction with fetal growth restriction, maternal endothelial dysfunction, and chronic immune activation. The mechanisms leading to the development of PE are unclear. However, it is thought that shallow trophoblast invasion and insufficient remodeling of uterine spiral arteries result in placental ischemia. Consequently, an immune imbalance characterized by increases in proinflammatory CD4+ T cells and cytokines along with decreases in regulatory T cells and anti-inflammatory cytokines occurs. This imbalance leads to chronic inflammation and ensuing oxidative stress, proinflammatory cytokines, and autoantibodies. Studies performed in our laboratories, using the Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia, have demonstrated a role for this immune imbalance to mediate PE pathophysiology and identified potential mechanisms of immunoregulation that may be of benefit in the treatment of PE. Therefore, the purpose of this commentary is to review studies demonstrating the positive effects of immunoregulatory factors in the RUPP rat model of PE. Restoration of the immune balance in PE may be a potential strategy for the development of therapeutic interventions that could improve maternal and fetal outcomes associated with this maternal syndrome.

Abstract 316: Cell-Matrix Contacts Regulate Age-Associated Cardiac Function

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ayla O Sessions ◽  
Gaurav Kaushik ◽  
Anthony Cammarato ◽  
Adam Engler
Keyword(s):  
Cardiac Function ◽  
Collagen Iv ◽  
Cardiac Performance ◽  
Model Organisms ◽  
Mechanical Function ◽  
Heart Tube ◽  
Cell Matrix ◽  
Intercalated Discs ◽  
Ecm Proteins ◽  
Ventral Muscle

An increased deposition of ECM is observed in all advanced age heart failure patients. Therefore, it is necessary to investigate the effect of extracellular remodeling on mechanical function in genetically tractable, rapidly aging, and simple model organisms such as Drosophila melanogaster . The bilayered design of the Drosophila heart-tube makes it an easier model in which to study the interplay between ECM and cardiomyocytes as they regulate contraction. Here we present data from two common wildtype strains of Drosophila exhibiting different aging profiles in terms of cytoskeletal and ECM regulation and remodeling. Using a recently developed nanoindentation method to measure cardiomyocyte stiffness of intact Drosophila hearts, we have found that while yellow-white ( yw ) flies show midline stiffening at the intercalated discs (ICD) presenting a clear diastolic dysfunction with age, the white-1118 ( w1118 ) flies exhibit no ICD stiffening, but show an increase in thickness of the ECM layer between the ventral muscle (VM) and cardiomyocytes (CM). Paired with increased expression of ECM proteins, the w1118 Drosophila line may provide a good model for exploring the effect of cell-ECM contacts on regulating cardiac function with age. Knock-down of integral ECM genes LamininA and Viking (Collagen IV) result in no effect on cardiac performance in juvenile flies but causes a decrease in underlying cardiomyocyte stiffness and an increase in the contractile irregularity of heart beats. This suggests that the cell-ECM contacts in the basement membrane are intimately tied to coupling of the cardiomyocytes of the Drosophila heart-tube, which may have larger implications for elderly patients suffering from myocardial fibrosis and experiencing cardiomyocyte decoupling and resultant arrhythmias.

scholarly journals Epigallocatechingallate Inhibits Migration of Human Uveal Melanoma Cells via Downregulation of Matrix Metalloproteinase-2 Activity and ERK1/2 Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Chi-Wu Chang ◽  
Yi-Hsien Hsieh ◽  
Wei-En Yang ◽  
Shun-Fa Yang ◽  
Yueqin Chen ◽  
...  
Keyword(s):  
Western Blot ◽  
Uveal Melanoma ◽  
Gelatin Zymography ◽  
Melanoma Cells ◽  
Matrix Metalloproteinase 2 ◽  
Pcr Analysis ◽  
Signal Pathways ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Uveal Melanoma Cell

The effects of epigallocatechingallate (EGCG) on the migration and expression of MMP-2 of uveal melanoma cells have not been reported. We studied this effect and relevant signaling pathways in a human uveal melanoma cell line (M17). MTT study found that EGCG did not affect the cell viability of M17 cells up to 100 µM. Wound-healing assay showed that EGCG significantly reduced the migration of melanoma cells in a dose-dependent manner from 20 to 100 µM. Gelatin zymography showed that secreted MMP-2 activity was dose-dependently inhibited by EGCG, whereas the MMP-2 expression at protein and mRNA levels was not affected as determined by western blot and RT-PCR analysis. EGCG significantly increased the expressions of MMP-2 endogenous inhibitors (TIMP-2 and RECK) in M17 cells. Western blot analysis of MAPK signal pathways showed that EGCG significantly decreased phosphorylated ERK1/2 levels, but not p38 and JNK levels, in melanoma cells. ERK1/2 inhibitors also reduced the migration and activity of MMP-2 in M17 cells. The present study suggested EGCG at nontoxic levels could inhibit migration of melanoma cells via downregulation of activities of secreted MMP-2 through the inhibition of the ERK1/2 phosphorylation. Therefore, EGCG may be a promising agent to be explored for the prevention of metastasis of uveal melanoma.

Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy

2008 ◽  
Vol 294 (1) ◽  
pp. H272-H284 ◽  
Author(s):  
Vsevolod Telezhkin ◽  
Tara Goecks ◽  
Adrian D. Bonev ◽  
George Osol ◽  
Natalia I. Gokina
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Late Pregnancy ◽  
Intraluminal Pressure ◽  
Delayed Rectifier ◽  
Myogenic Tone ◽  
Channel Activity ◽  
Voltage Gated ◽  
Uterine Arteries ◽  
Increased Pressure

Increased pressure-induced (myogenic) tone in small uteroplacental arteries from late pregnant (LP) rats has been previously observed. In this study, we hypothesized that this response may result from a diminished activity of vascular smooth muscle cell (SMC) voltage-gated delayed-rectifier K+ (Kv) channels, leading to membrane depolarization, augmented Ca2+ influx, and vasoconstriction (tone). Elevation of intraluminal pressure from 10 to 60 and 100 mmHg resulted in a marked, diltiazem-sensitive rise in SMC cytosolic Ca2+ concentration ([Ca2+]i) associated with a vasoconstriction of uteroplacental arteries of LP rats. In contrast, these changes were significantly diminished in uterine arteries from nonpregnant (NP) rats. Gestational augmentation of pressure-induced Ca2+ influx through L-type Ca2+ channels was associated with an enhanced SMC depolarization, the appearance of electrical and [Ca2+]i oscillatory activities, and vasomotion. Exposure of vessels from NP animals to 4-aminopyridine, which inhibits the activity of Kv channels, mimicked the effects of pregnancy by increasing pressure-induced depolarization, elevation of [Ca2+]i, and development of myogenic tone. Furthermore, currents through Kv channels were significantly reduced in myocytes dissociated from arteries of LP rats compared with those of NP controls. Based on these results, we conclude that decreased Kv channel activity contributes importantly to enhanced pressure-induced depolarization, Ca2+ entry, and increase in myogenic tone present in uteroplacental arteries from LP rats.

scholarly journals Inverted formin 2 regulates intracellular trafficking, placentation, and pregnancy outcome

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Katherine Young Bezold Lamm ◽  
Maddison L Johnson ◽  
Julie Baker Phillips ◽  
Michael B Muntifering ◽  
Jeanne M James ◽  
...  
Keyword(s):  
Intracellular Trafficking ◽  
Gestational Hypertension ◽  
Fetal Distress ◽  
Trophoblast Invasion ◽  
Vascular Density ◽  
Placental Perfusion ◽  
Healthy Pregnancy ◽  
Umbilical Artery Doppler ◽  
Placental Ischemia ◽  
Extravillous Trophoblasts

Healthy pregnancy depends on proper placentation—including proliferation, differentiation, and invasion of trophoblast cells—which, if impaired, causes placental ischemia resulting in intrauterine growth restriction and preeclampsia. Mechanisms regulating trophoblast invasion, however, are unknown. We report that reduction of Inverted formin 2 (INF2) alters intracellular trafficking and significantly impairs invasion in a model of human extravillous trophoblasts. Furthermore, global loss of Inf2 in mice recapitulates maternal and fetal phenotypes of placental insufficiency. Inf2−/− dams have reduced spiral artery numbers and late gestational hypertension with resolution following delivery. Inf2−/− fetuses are growth restricted and demonstrate changes in umbilical artery Doppler consistent with poor placental perfusion and fetal distress. Loss of Inf2 increases fetal vascular density in the placenta and dysregulates trophoblast expression of angiogenic factors. Our data support a critical regulatory role for INF2 in trophoblast invasion—a necessary process for placentation—representing a possible future target for improving placentation and fetal outcomes.

scholarly journals In Vitro Evidence Suggests Activin-A May Promote Tissue Remodeling Associated with Human Luteolysis

Endocrinology ◽  
2007 ◽  
Vol 148 (8) ◽  
pp. 3730-3739 ◽  
Author(s):  
Michelle Myers ◽  
Eva Gay ◽  
Alan S. McNeilly ◽  
Hamish M. Fraser ◽  
W. Colin Duncan
Keyword(s):  
Granulosa Cells ◽  
Primary Cultures ◽  
Gelatin Zymography ◽  
Activin A ◽  
Primary Cell ◽  
Matrix Metalloproteinase 2 ◽  
Corpora Lutea ◽  
Type I ◽  
Rt Pcr ◽  
Maternal Recognition Of Pregnancy

Luteolysis in women is associated with an up-regulation of the expression and activity of matrix metalloproteinase-2 (MMP-2), which is inhibited by human chorionic gonadotropin (hCG) during maternal recognition of pregnancy. Because the primary source of MMP-2 is fibroblasts that do not express LH/hCG receptors, we aimed to investigate the regulation of MMP-2. Women with regular cycles having hysterectomy for nonmalignant conditions and women undergoing oocyte retrieval for assisted conception were used in this current study. Novel primary cultures and cocultures of luteinized granulosa cells and fibroblast-like cells in conjunction with human corpora lutea from different stages of the luteal phase were used to investigate the role of activin-A in the corpus luteum. The effect of hCG, activin-A, and follistatin on MMP-2 activity and expression was assessed by gelatin zymography and quantitative RT-PCR in primary cell cultures. Confirmation of signaling pathways involved in the activation of MMP-2 was assessed by immunofluorescence, RT-PCR, and quantitative RT-PCR. In primary cell culture, steroidogenic cells secrete activin-A and its inhibitors, inhibin-A and follistatin. Follistatin expression is up-regulated by hCG (P < 0.05). The fibroblast-like cells producing MMP-2 have the machinery for activin reception, expressing both type I and type II activin receptors and Smad proteins. Activin-A up-regulated both activity and expression of MMP-2 in fibroblast-like cells (P < 0.05). This activity was inhibited in cocultures of luteinized granulosa cells and fibroblast-like cells in the presence of hCG (P < 0.05) or follistatin (P < 0.01). Activin-A is an excellent candidate for an effector molecule in human luteolysis whose paracrine action is inhibited during maternal recognition of pregnancy.

scholarly journals Gelatinases Increase in Bleomycin-induced Systemic Sclerosis Mouse Model

2019 ◽  
Author(s):  
Fatemeh Vafashoar ◽  
Kazem Mousavizadeh ◽  
Hadi Poormoghim ◽  
Abbas Tavasoli ◽  
Tahereh Musavi Shabestari ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mouse Model ◽  
Matrix Metalloproteinase ◽  
Gelatin Zymography ◽  
Gelatinolytic Activity ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Tissue Sections ◽  
Tissue Homogenates ◽  
And Control

Systemic sclerosis is a fibrotic autoimmune disease in which aberrant remodeling of the extracellular matrix in organs disturbs their functionalities. The aim of this study was to investigate the expression of gelatinases on systemic sclerosis. Consequently, a mouse model of systemic sclerosis was employed and the gelatinolytic activity of gelatinases was evaluated on the fibrotic tissues of this model. Two groups of ten mice were considered in this work: a group of systemic sclerosis model and control group. For the generation of systemic sclerosis model, mice received bleomycin, while the control group was subjected to phosphate buffered saline (PBS) reception. Mice were tested for fibrosis by using trichrome staining, hydroxyproline measurement and α-SMA detection in tissue sections. Additionally, the gelatinolytic activity of matrix metalloproteinase 2 and matrix metalloproteinase 9 were measured using gelatin zymography in lungs and skin tissue homogenates. The obtained results indicated that subcutaneous injection of bleomycin-induced fibrosis in skin and lung tissues of mice. Pro and active forms of matrix methaloproteinase 9 were increased in fibrotic lung tissues (p<0.05 and p<0.01, respectively), while, the gelatinolytic activity of MMP2 was unaffected in these tissues. Additionally, in skin tissues of bleomycin-treated animals, both pro and active forms of MMP9 and MMP2 were increased (p<0.05). Pro and active forms of gelatinases increase differently in skin and lung tissues of bleomycin-induced scleroderma.  

scholarly journals EFFECT OF THE ENZYME-CONTAINING POLYMERIC NANOPARTICLES ON MMP-2 ACTIVITY DURING BURN WOUND HEALING IN RATS WITH STREPTOZOTOCIN-INDUCED DIABETES

2021 ◽  
Vol 17 (2) ◽  
pp. 12-19
Author(s):  
O.I. Myronenko ◽  
T.I. Panova ◽  
L.V. Natrus ◽  
S.V. Verevka
Keyword(s):  
Diabetes Mellitus ◽  
Extracellular Matrix ◽  
Wound Healing ◽  
Gelatin Zymography ◽  
Matrix Metalloproteinase 2 ◽  
Diabetic Wound ◽  
Burn Wound ◽  
Impaired Wound Healing ◽  
Chronic Hyperglycemia ◽  
Streptozotocin Induced Diabetes

Relevance. Diabetic foot syndrome is a common complication that is characterized by the development of chronic ulcers. Among the mechanisms of impaired wound healing, the leading role is played by disturbance of extracellular matrix homeostasis: chronic hyperglycemia, on the one hand, promotes the formation of so-called advanced glycation end products (AGEs), which mediate pro-inflammatory activation of immune cells, and on the other hand, inhibits fibroblasts proliferation and collagen production, disrupts the migration of keratinocytes and endothelial cells. Therefore, the elimination of AGEs is a pathogenetic approach in diabetic wound treatment. For this purpose, a composite consisting of polyspecific microbial proteinases fixed on polymeric porous nanoparticles was developed. The activity of matrix metalloproteinase-2 (MMP-2) was chosen as a prognostic indicator of chronic wound healing. Objective: to study the activity of MMP-2 in the tissues of the burn wound of rats with simulated diabetes mellitus under the influence of enzyme-containing nanoparticles. Materials and methods. N = 48 Wistar rats were used in the experiment. Diabetes mellitus was induced by administration of 50 mg/kg of streptozotocin. To model the wound in rats, a standard animal model of thermal burns by Walker and Mason was used. Thermal damage corresponded to the II-IIIA degree of burns, and occupied 19±1.6% of the total area of ​​animal skin. Rats were divided into two groups of 24 animals each: the DM group did not receive any treatment, and rats from the DM+T group were daily applied to the burn wound with the mentioned composite (enzyme-containing nanoparticles). Animals were removed from the experiment on days 3, 7, 14 and 21 of observation. The activity of MMP-2 in the tissues of the burn wound of diabetic rats was studied by gelatin zymography, expressed in arbitrary units (AU). Statistical data processing was performed in the software package SPSS Statistics Base, v.22 with Student and Scheffe tests. Results. The level of activity of MMP-2 in the tissues of the burn wound of rats in the DM group on the 3rd day of the study was 4.9 ± 1.3 AU, increased by 7 days (p <0.01) and reached a maximum level of 52.55 ± 3.06 AU at day 14 (p <0.01). On day 21, the activity of the test enzyme decreased by 8.5 AU (p <0.01), compared to day 14. On day 3 of the study in the DM+T group, the activity of MMP-2 in the diabetic wound was 15.93 ± 2.68 AU and gradually decreased (p <0.01) to 5.67 ± 2.67 AU on day 14. However, on day 21, the second peak (p <0.01) of the activity of the studied enzyme was observed - 33.64 ± 4.1 AU. When comparing the two groups (DmM and DM+T) on day 3 of the study, the activity of MMP-2 in the tissues of the burn wound of rats in the DM+T group was three times higher (p <0.01) than in the DM group. But from the 7th day the activity of MMP-2 in the DM group was higher than the DM+T group. On day 21 of the study, the level of MMP-2 in the DM group remained higher (p <0.01) than in the DM+T group. Conclusions. The use of enzyme-containing nanoparticles provides effective degradation of glycosylated components of the extracellular matrix (AGEs), thereby reducing the inflammatory process and activity of MMP-2, and promoting wound healing in rats with streptozotocin-induced diabetes.

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