Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

Correlation of matrix metalloproteinase－2, －9, tissue inhibitor－1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase 2, 9 (MMP 2, MMP 9), tissue inhibitor 1 of matrix metalloproteinase (TIMP 1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP 2, MMP 9, TIMP 1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship ( P <0.05) between the expression of MMP 2 and MMP 9, TIMP 1 and CD44v6, HER2/neu and MMP 9, MMP 2 and p53. Up regulation of MMP 2 was accompanied by advanced T stage ( P <0.01) . There was also a trend of MMP 2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence( P <0.05). The expression of TIMP 1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non keratinizing SCC than that in basaloid SCC( P <0.05). These findings suggested that MMP 2 and MMP 9, HER2/neu and MMP 9, MMP 2 and p53 had a coordinate function in aggression of tumor; that MMP 2 had a more important function than MMP 9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.

Do different bariatric surgical procedures influence plasma levels of matrix metalloproteinase-2,-7,and-9 among patients with type 2 diabetes mellitus?

BACKGROUND Bariatric surgery is an efficient strategy for body weight and type 2 diabetes mellitus(T2 DM) management. Abnormal lipid deposition in visceral organs,especially the pancreas and liver, might cause beta-cell dysfunction and insulin resistance. Extracellular matrix(ECM) remodeling allows adipose expansion, and matrix metalloproteinases(MMPs) play essential roles in ECM construction.MMP-2 and MMP-9 are the substrates of MMP-7. Different studies have reported that MMP-2,-7, and-9 increase in patients with obesity and metabolic syndromes or T2 DM and are considered biomarkers in obesity and hyperglycemia patients.AIMTo prospectively investigate whether MMP-2, MMP-7, and MMP-9 differ after two bariatric surgeries: Gastric bypass(GB) and sleeve gastrectomy(SG).METHODS We performed GB in 23 and SG in 19 obese patients with T2 DM. We measured body weight, waist circumference, body mass index(BMI), and serum concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood sugar(FBS),hemoglobin A1 c(Hb A1 c), C-peptide, homeostasis model assessments of insulin resistance, and MMP-2, MMP-7, and MMP-9 levels at baseline and at 3, 12, and 24 mo post-operation.RESULTS Twenty-three patients aged 44.7 ± 9.7 years underwent GB, and 19 patients aged40.1 ± 9.1 years underwent SG. In the GB group, BMI decreased from 30.3 ± 3.4 to24.4 ± 2.4 kg/m2, Hb A1 c decreased from 9.2% ± 1.5% to 6.7% ± 1.4%, and FBS decreased from 171.6 ± 65.0 mg/d L to 117.7 ± 37.5 mg/d L 2 years post-operation(P < 0.001). However, the MMP-2, MMP-7, and MMP-9 levels pre-and post-GB were similar even 2 years post-operation(P = 0.107, 0.258, and 0.466,respectively). The SG group revealed similar results: BMI decreased from 36.2 ±5.1 to 26.9 ± 4.7 kg/m2, Hb A1 c decreased from 7.9% ± 1.7% to 5.8% ± 0.6%, and FBS decreased from 138.3 ± 55.6 mg/d L to 95.1 ± 3.1 mg/d L(P < 0.001). The serum MMP-2,-7, and-9 levels pre-and post-SG were not different(P = 0.083,0.869, and 0.1, respectively).CONCLUSION Improvements in obesity and T2 DM induced by bariatric surgery might be the result of MMP-2,-7, or-9 independent pathways.

Correlation of RECK with Matrix Metalloproteinase-2 in Regulation of Trophoblast Invasion of Early Pregnancy

To study the role of the reversion-inducing-cysteine-rich protein with Kazal motifs （RECK） gene and matrix metalloproteinase-2 （MMP-2） in the regulation of trophoblast invasion of early pregnancy. Immunohistochemistry, Western blot and gelatin zymography were used to detect the RECK protein expression localization, expression level and MMP-2 activation level in the placental tissues harvested from 52 normal pregnant women （27 in the early pregnancy, 25 in the term pregnancy）. Immunohistochemistry showed that RECK expression was found both in villous tissues of early pregnancy group and term pregnancy group and was mainly observed in cell membrane and cytoplasm of cytotrophoblasts and syneytiotrophoblasts. RECK expression increased with gestational time. RECK expression of early pregnancy group was significantly lower than that of term pregnancy group （P〈0.05）. RECK expression was significantly lower in cellular column （CC） with invasion ability. Western blot showed that the RECK protein expression in early pregnancy group was significantly lower than that in term pregnancy （P〈0.05）. The optical density values of RECK protein expression in early pregnancy group and term pregnancy group were 1.35±0.14 and 2.68±0.26, respectively, while MMP-2 activation ratio was contrary to RECK protein expression and decreased with the gestation time （P〈0.01）. The MMP-2 activation ratios of early pregnancy group and term pregnancy group were 0.46±0.05 and 0.10±0.02, respectively. The expression of the tumor inhibitory gene RECK was positively related with the invasion ability of trophoblasts, while the invasion gene MMP-2 was negatively related with the ability. The interaction between RECK and MMP-2 may play an important role in the regulation of the trophoblast invasion in early pregnancy.

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China

Matrix metalloproteinase 2(MMP2) has been shown to play an important role in several steps of cancer development.The-1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele,and the CC genotype in the MMP2 promoter has been reported to associate with the development of several cancers.To assess the contribution of the MMP2-1306C/T polymorphism to the risk of nasopharyngeal carcinoma(NPC),we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele analysis.We found that subjects with the CC genotype had an increased risk(OR = 1.55,95% CI = 1.05-2.27) of developing NPC compared to those with the CT or TT genotypes.Furthermore,we found that the risk of NPC was markedly increased in subjects who were smokers(OR = 15.04,95% CI = 6.65-33.99),heavy smokers who smoked ≥20 pack-years(OR = 18.66,95% CI = 7.67-45.38),or young(<60 years) at diagnosis(OR = 1.52,95% CI = 1.01-2.29).Our results provide molecular epidemiological evidence that the MMP2-1306C/T promoter polymorphism is associated with NPC risk,and this association is especially noteworthy in heavy smokers.

Distribution and relative activity of matrix metalloproteinase-2 in human coronal dentin

The presence of matrix metalloproteinase-2 （MMP-2） in dentin has been reported, but its distribution and activity level in mature human coronal dentin are not well understood. The purpose of this study was to determine the MMP-2 distribution and relative activity in demineralized dentin. Crowns of twenty eight human molars were sectioned into inner （ID）, middle （MD）, and outer dentin （OD） regions and demineralized. MMP-2 was extracted with 0.33 mol·L-1 EDTA/2 mol·L-1 guanidine-HCl, pH 7.4, and MMP-2 concentration was estimated with enzyme-linked immunoabsorbant assay （ELISA）. Further characterization was accomplished by Western blotting analysis and gelatin zymography. The mean concentrations of MMP-2 per mg dentin protein in the dentin regions were significantly different （P=0.043）： 0.9 ng （ID）, 0.4 ng （MD）, and 2.2 ng （OD）, respectively. The pattern of MMP-2 concentration was OD〉ID〉MD. Western blotting analysis detected -66 and -72 kDa immunopositive proteins corresponding to pro- and mature MMP-2, respectively, in the ID and MD, and a -66 kDa protein in the OD. Gelatinolytic activity consistent with MMP-2 was detected in all regions. Interestingly, the pattern of levels of Western blot immunodetection and gelatinolytic activity was MD〉ID〉OD. The eoneentration of MMP-2 in human coronal dentin was highest in the region of dentin that contains the dentinoenamel junction and least in the middle region of dentin. However, levels of Western blot immunodetection and gelatinolytic activity did not correlate with the estimated regional concentrations of MMP-2, potentially indicating region specific protein interactions.

血清MMP2/TIMP2比值与老年2型糖尿病患者并发AS的相关性分析

目的探讨血清基质金属蛋白酶-2/金属蛋白酶组织抑制因子-2(MMP2/TIMP2)比值与老年2型糖尿病(T2DM)患者并发主动脉硬化(AS)之间的关系。方法回顾性分析2022年1月至2023年4月万宁市人民医院收治的180例初次诊断为T2DM的老年患者的临床资料,并根据是否并发AS[颈动脉-股动脉脉搏波传导速度(cfPWV)>10 m/s]分为AS组(n=69)和非AS组(n=111)。另选取同时期来院体检健康者采用倾向性评分法匹配90例为对照组。比较3组对象的一般资料、实验室指标以及血清MMP2、TIMP2水平和MMP2/TIMP2比值。采用Spearman相关分析探究老年T2DM患者cfPWV与各项指标的相关性。采用多因素logistic回归模型分析,老年T2DM患者并发AS的影响因素。绘制受试者工作特征(ROC)曲线,分析并比较MMP2/TIMP2比值与多指标联合检测对老年T2DM患者并发AS的诊断价值。结果非AS组稳态模型胰岛素抵抗指数(HOMA-IR)、血清三酰甘油(TG)、MMP2水平及MMP2/TIMP2比值高于对照组,血清TIMP2水平低于对照组,差异有统计学意义(P<0.05)。AS组年龄、合并高血压比例高于非AS组(P<0.05)。AS组HOMA-IR、血清TG、MMP2水平及MMP2/TIMP2比值高于对照组和非AS组,血清TIMP2水平低于对照组和非AS组,差异均有统计学意义(P<0.05)。相关性分析结果显示,非AS组患者的cfPWV与HOMA-IR、TC、LDL-C、MMP2、MMP2/TIMP2比值呈正相关(r=0.217、0.264、0.216、0.197、0.703,P<0.05),与TIMP2呈负相关(r=-0.524,P<0.01);AS组患者cfPWV与MMP2、MMP2/TIMP2比值呈正相关(r=0.659、0.857,P<0.01),与TIMP2呈负相关(r=-0.532,P<0.01)。logistic回归分析显示,年龄增长(OR=1.108,95%CI:1.022~1.201,P=0.012)、高血压病(OR=2.877,95%CI:1.174~7.051,P=0.021)及MMP2/TIMP2比值升高(OR=5.147,95%CI:2.392~11.074,P<0.001)是老年T2DM患者并发AS的的独立危险因素。ROC曲线分析结果显示,MMP2/TIMP2比值及多指标联合检测诊断老年T2DM患者并发AS的曲线下面积分别为0.850(95%CI:0.789~0.899,P<0.01)和0.886(95%CI:0.831~0.929,P<0.01),灵敏度分别为73.91%、82.61%,特异度分别为89.19%、82.88%,约登指数分别为0.631、0.655。多指标联合检测的诊断效能明显大于MMP2/TIMP2比值,差异具有统计学意义(Z=2.233,P=0.026)。MMP2/TIMP2比值诊断老年T2DM患者并发AS的最佳截断值为3.23。结论MMP2/TIMP2比值升高为老年T2DM患者并发AS的独立危险因素,对老年T2DM并发AS的诊断有辅助价值,多指标联合检测可提高诊断效能。

Vascular Endothelial Growth Factorl65-regulated Nasopharyngeal Carcinoma Cell Lines Invasion and Migration Involve Expression and Activation of Matrix Metalloproteinase-2

The effect of vascular endothelial growth factor （VEGF） overexpression on matrix metalloproteinase-2 （MMP-2） in nasopharyngeal carcinoma （NPC） cells in vitro and the possible mechanism involved were investigated, and the correlation between the expression of VEGF and MMP-2 in NPC evaluated. The NPC cells were transfected with PAd-trackVEGF165 plasmid. The expression levels of VEGF and MMP-2 mRNA and protein in NPC cells were detected by semi-quantitative RT-PCR and Western blot respectively. It was found that the expression of VEGF and MMP-2 mRNA and protein was significantly increased in NPC cells after transfection of VEGF 165. It was concluded that the expression of VEGF was correlated to the in vitro invasion of NPC cells, and the induction of MMP-2 by VEGF was a key process of NPC cell invasion.

MMP2基因多态性与盐酸多奈哌齐治疗阿尔茨海默病的血药浓度和效果的关系

目的 探讨基质金属蛋白酶2(Matrix metalloproteinase 2,MMP2)基因单核苷酸多态性对盐酸多奈哌齐在阿尔茨海默病(Alzheimer′s disease, AD)中的血药浓度和治疗效果的影响。方法 选择2020年1月-2023年1月于徐州市东方人民医院老年精神科就诊治疗的97例AD患者为AD组,以同期进行体检的100名健康老年人为健康对照组。所有患者入院接受5 mg/d的盐酸多奈哌齐治疗,连续30 d,将盐酸多奈哌齐剂量增至10mg/d,连续150 d。治疗前后采用简明精神状况量表(Mini-mental state examination, MMSE)评估患者的认知功能,依据最后一次MMSE评分与第一次MMSE评分相比是否下降,分为应答组和未应答组。治疗6个月后采用高效液相色谱-串联质谱联用法测定两组血液中盐酸多奈哌齐血药浓度。采用实时定量PCR(Polymerase chain reaction, PCR)和限制性片段长度多态性分析检测血液中MMP2基因rs243865(C>T)、rs2285053(C>T)基因分型。结果 与健康对照组比较,AD组MMP2基因rs243865、rs2285053基因型分布,rs243865位点遗传模型差异无统计学意义(P>0.05),rs2285053位点显性模型差异有统计学意义(P<0.05)。经盐酸多奈哌齐治疗后,与未应答组比较,应答组MMP2基因rs243865基因型分布、遗传模型及隐性模型差异均无统计学意义(P>0.05),rs2285053基因型分布、相加模型、显性模型差异有统计学意义(P<0.05)。不同MMP2基因位点rs243865位点基因型AD患者的盐酸多奈哌齐血药浓度比较差异无统计学意义(P>0.05)。与rs2285053位点TT基因型AD患者比较,CC、CT基因型患者的盐酸多奈哌齐血药浓度增大,差异有统计学意义(P<0.05)。未应答组与应答组间盐酸多奈哌齐血药浓度差异无统计学意义(P>0.05)。结论 MMP2基因rs2285053位点变异与盐酸多奈哌齐治疗AD的血药浓度和疗效有关,对于临床治疗用药有一定指导价值。

突发性耳聋患者血清VCAM-1、ENA-78、MMP-2水平变化及检测意义

目的:探讨突发性耳聋患者血清血管细胞黏附分子-1(VCAM-1)、上皮中性粒细胞活化肽-78(ENA-78)、基质金属蛋白酶-2(MMP-2)水平变化及检测意义。方法:选取接受治疗的突发性耳聋患者136例为观察组,另选取同期体检健康者136例为对照组。采用ELISA法测定血清VCAM-1、ENA-78、MMP-2水平。根据听力损失程度将患者分为轻度组(46例)、中度组(51例)和重度组(39例)。根据治疗效果将患者分为疗效良好组(82例)和疗效不良组(54例)。比较观察组和对照组血清VCAM-1、ENA-78、MMP-2水平。比较不同听力损失程度及治疗效果患者血清VCAM-1、ENA-78、MMP-2水平。绘制受试者工作特征(ROC)曲线分析血清VCAM-1、ENA-78、MMP-2对突发性耳聋患者疗效不良的预测价值。结果:观察组血清VCAM-1、ENA-78、MMP-2水平高于对照组(均P<0.05)。与轻度组比较,中度和重度组血清VCAM-1、ENA-78、MMP-2水平逐渐升高(均P<0.05)。疗效良好组和疗效不良组患者临床资料比较差异无统计学意义(均P>0.05)。与疗效良好组比较,疗效不良组患者血清VCAM-1、ENA-78、MMP-2水平升高(均P<0.05)。血清VCAM-1、ENA-78、MMP-2三者联合预测突发性耳聋患者疗效不良的AUC高于血清单独指标预测的AUC(均P<0.05)。结论:突发性耳聋患者血清VCAM-1、ENA-78、MMP-2水平升高,与听力损失程度有关,三者联合对突发性耳聋患者治疗效果的预测价值较高。

Immunohistochemical Studies of the Expression of Matrix Metalloproteinase-2 and Metalloproteinase-9 in Human Prostate Cancer

To study the expression of matrix metalloproteinase 2 and 9 in human prostate cancer, matrix metalloproteinase 2 and 9 were immunohistochemically detected in tissues of prostate cancer and benign prostatic hyperplasia (BPH). Our results showed that matrix metalloproteinase 2 and 9 levels in prostate cancer were much higher than those in tissues of BPH, with the cancer invasion being positively correlated with the expression of the metalloproteinases. It is concluded that matrix metalloproteinase 2 and 9 are better molecular markers, which are of help in the diagnosis and prediction of prognosis of prostate cancer.

EXPRESSION OF MATRIX METALLOPROTEINASE-2 AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN HUMAN GLIOMA AND THEIR RELATION TO THE INVASION OF THE TUMOR

Objective To study the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in different grade human glioma. To investigate their relation to the pathological grade and invasion of the tumor. Methods The expression of MMP-2 and VEGF were determined by immunohistochemical technique in 48 cases of human glioma and 10 specimens of normal brain tissue. Results The expression levels of MMP-2 and VEGF in human glioma were positively related to tumor grades (P<0.01), and their expressions in the glioma of grade Ⅲ and Ⅳ were significantly different from those in the glioma of grade Ⅰ-Ⅱand normal brain tissue (P<0.01). The expression of MMP-2 was positively correlated to that of VEGF (P<0.01). Conclusion MMP-2 and VEGF were highly expression in human glioma and were positively related to the tumor grades. The synergic interaction of MMP-2 and VEGF promoted the angiogenesis and invasion of human glioma.

Human ciliary muscle cell responses to kinins:Activation of ERK1/2 and pro-matrix metalloproteinases secretion

AIM To study activation of extracellular signal-regulated kinase-1/2(ERK1/2) and pro-matrix metalloproteinases(pro-MMPs) secretion from isolated primary human ciliary muscle(h-CM) cells in response to bradykinin(BK) and other agonists. METHODS Serum-starved h-CM cells were challenged with vehicle, BK agonists or antagonists. Cell lysates were evaluated for phosphorylated ERK1/2 using homogeneous timeresolved fluorescence technology based on a sandwich immunoassay. Rabbit polyclonal anti-pro-MMP antibodies were used to measure pro-MMPs using immunoblot analysis.RESULTS A 10 min incubation time using 5 × 104 h-CM cells/well was optimum condition for studying stimulation of ERK1/2 phosphorylation. BK(100 nmol/L) caused a 1.86 ± 0.26 fold(n = 3) increase in ERK1/2 phosphorylation above baseline. BK analogs, Met-Lys-BK and RMP-7(100 nmol/L), also stimulated ERK1/2 phosphorylation by 1.57 ± 0.04 and 1.55 ± 0.09 fold, respectively. However, DesArg9-Bradykinin, a B1 receptor-selective agonist(0.1-1 μmol/L), was essentially inactive. HOE-140 or WIN-64338(B2-antagonists) appreciably blocked phosphorylation of ERK1/2 induced by various BK agonists. Pre-treatmentof cells with a prostaglandin(PG) synthase inhibitor(bromfenac; 1 μmol/L) failed to alter kinin-induced ERK1/2 activation. BK and a non-peptide BK agonist(FR-190997)(10 nmol/L-1 μmol/L) also enhanced pro-MMPs secretion(pro-MMP-1 > pro-MMP-3 > pro-MMP-2; 1.45-1.75-fold over baseline) from h-CM cells. CONCLUSION These collective data suggest that B2 kinin receptors initiate signaling in h-CM cells by a relatively rapid mechanism(within minutes) involving ERK1/2 activation which in turn regulates MMPs production(within hours). The latter process does not involve PGs.

Rosiglitazone uppresses lipopolysaccharide-induced matrix metalloproteinase-2 activity in rat aortic endothelial cells via rasMEK1/2 signaling

ix metalloproteinase(MMPs) plays a key role in the pathogenesis of chronic inflammatory disease,such as atherosclerosis.Among MMPs,MMP-2 is regarded as a major proteinase in atherosclerotic plaque lesions.Peroxisome proliferator activated receptor-gamma(PPARg) ameliorates oxidative stress and the inflammatory response.The aim of the present study was to evaluate the effect of Rosiglitazone on Lipopolysaccharide(LPS)-induced MMP-2 activation as well as its possible mechanism.LPS-induced MMP-2 activity was inhibited by Rosiglitazone(PPARg agonist) in the rat aortic endothelial cells(RAEC).LPS-induced MMP-2 activation was diminished no matter exposure to NF-kB Activation Inhibitor II(JSH-23)or Ras inhibitor,farnesylthiosalicylic acid(FTS). Further study shows that LPS-induced activation of Phospho-Rho A and Phospho-MEKl/2 were significantly inhibited by Rosiglitazone.The activation of NF-kB p65 in the nuclear extract of cells was also significantly suppressed by Rosiglitazone, moreover,the expression of NF-κB p65 was partly activated by GW9662(PPARg antagonist).NF-kB DNA binding activity was also demolished by Rosiglitazone.In summary,our data showed that PPARg agonist,Rosiglitazone suppresses LPS-activated MMP-2 secretion via Ras-MEK1/2 signaling pathways and NF-kB activation.PPARg agonist and Ras-MEK1/2 pathway may be another potential therapeutic target for the disease induced by chronic inflammation.

Cryptotanshinone attenuates isoprenaline-induced cardiac fibrosis in the mouse associated with upregulation and activation of matrix metalloproteinase-2

Objectives The impairment of matrix metallopro- teinase-2(MMP-2)has been associated with the development of cardiac fibrosis.Although the Chinese herb Salvia miltior-rhiza has been widely used in patients with cardiovascular disorders,the mechanisms involved have not been elucidated. The purpose of the present study was to determine whether the administration of cryptotanshinone,an active ingredient of Salvia miltiorrhiza,could prevent the cardiac fibrosis induced by isoprenaline and to investigate the underlying mechanisms. Methods and Results Male C57BL/6 mice were submitted to receive daily injection of 0.9%saline,3 mg/kg isoprenaline, or isoprenaline plus 20 mg/kg cryptotanshinone by gastric gavage for 2 weeks.Herein,we demonstrate that cryptotanshinone can significantly ameliorate the isoprenaline-induced cardiac fibrosis,which was associated with marked up-regulation and activation of MMP-2 in ventricular myocardium. Additionally,we demonstrate that cryptotanshinone can dose-dependently upregulate and activate MMP-2 in cultured cardiac fibroblast.Moreover,incubation with cryptotanshinone also can prevent isoprenaline-induced downregulation and inactivation of MMP-2 in cultured cardiac fibroblast. Conclusions Taken together,our data suggest that cryptotanshinone may become a novel and potent antifibrotic agent. The present findings might further our understanding of the role of MMP-2 in cardiac fibrosis and antifibrotic mechanisms of cryptotanshinone.

冠状动脉粥样硬化斑块与MMP2、MMP9水平的关系

目的:探讨冠状动脉粥样硬化斑块与基质金属蛋白酶-2(MMP2)、基质金属蛋白酶-9(MMP9)水平的关系及经阿托伐他汀治疗后的水平变化。方法:选择2012年5月～2013年5月我院收治的患者72例,分为急性冠状动脉综合征(ACS)组40例,稳定型心绞痛(SA)组32例。采用酶联免疫吸附法检测所有患者治疗前后血清MMP2及MMP9水平,并比较ACS、SA患者治疗前后MMP2及MMP9水平的变化。结果:(1)治疗前ACS组患者MMP2和MMP9的水平高于SA组(P<0.05);(2)ACS和SA患者治疗前后MMP2和MMP9水平比较,差异有统计学意义(P<0.05);(3)ACS组患者冠脉斑块主要为Ⅱ型,而SA组患者冠脉斑块主要为Ⅰ型和Ⅲ型;(4)冠脉斑块中Ⅱ型斑块较Ⅰ、Ⅲ型斑块的MMP2及MMP9水平升高,差异具有统计学意义(P<0.05)。结论:MMP2及MMP9的水平与冠状动脉粥样硬化斑块密切相关;ACS、SA患者经过阿托伐他汀治疗后,血清MMP2及MMP9水平明显降低,以达到稳定动脉粥样硬化斑块的作用。

低氧和牙周炎对牙周组织中HIF-1α和MMP2表达的影响

目的研究低氧条件下HIF-1α、MMP2在大鼠牙周炎牙周组织中的表达及其与牙周炎的相关性,初步探讨HIF-1α与MMP2之间的关系。方法建立低氧牙周炎动物模型,40只大鼠采用简单随机化分组法分为常氧组、常氧牙周炎组、低氧组、低氧牙周炎组,每组10只,分别检测牙龈指数、菌斑指数、探诊深度及牙槽骨吸收度4项牙周炎临床指标;牙周组织切片HE染色观察牙周炎症程度;免疫组化及Western blot检测牙周组织中HIF-1α、MMP2的表达。结果牙周炎各临床指标及组织切片的HE染色均表明低氧牙周炎组大鼠牙周组织炎症程度最重;与常氧两组比较,低氧组均促进了牙周组织中HIF-1α、MMP2的表达(P<0.05);与非牙周炎组比较,牙周炎组HIF-1α、MMP2表达明显增加(P<0.05);低氧牙周炎组HIF-1α、MMP2表达最高(P<0.05)。结论低氧促进了牙周炎组织中HIF-1α、MMP2的表达,加速了牙周炎的发展进程。

甲状腺乳头状癌中MMP2、COX-2、VEGF和MVD的表达及临床意义

目的研究甲状腺乳头状癌(PTC)中环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)、基质金属蛋白酶(MMPs)表达和微血管密度(MVD)计数与PTC的临床病理特征之间的关系,并用以评估恶性程度、预后。方法运用免疫组化染色方法,检测32例PTC和18例正常甲状腺组织中的COX-2、VEGF、MMP2表达和MVD计数,并分析其与临床病理特征的关系。结果COX-2、VEGF、MMP2和MVD在PTC中的表达分别为(中位数和四分位距表示):M(Q3-Q1)=5(1),M(Q3-Q1)=5.5(2),M(Q3-Q1)=5.5(1)和M(Q3-Q1)=28(5.75),与对照组相比差异均有统计学意义(P<0.05)。COX-2、VEGF、MMP2、MVD的计数表达与患者的年龄、临床分期、淋巴结转移有关(P<0.05);COX-2与VEGF还与性别有关(P<0.05);VEGF、MMP2的表达及MVD的计数还与患者肿瘤大小有关(P<0.05)。COX-2、VEGF、MMP2和MVD在被膜浸润组中的表达分别为:M(Q3-Q1)=6(2),M(Q3-Q1)=6.5(2),M(Q3-Q1)=6(1.75)和M(Q3-Q1)=30(7.75),被膜未浸润组中的表达为:M(Q3-Q1)=5(1.75),M(Q3-Q1)=5(1.75),M(Q3-Q1)=5(1.75)和M(Q3-Q1)=26.5(4);COX-2、VEGF、MMP2和MVD在被膜浸润组与未浸润组之间的表达差异具有统计学意义(P<0.05)。PTC中COX-2、MMP2、VEGF和MVD的表达相互之间具有显著的正相关性(r>0.5)。结论甲状腺组织中MMP2、COX-2、VEGF的高表达可能促进了PTC的发生和肿瘤淋巴结转移;这与调控肿瘤新生血管有关。检测其表达对评估PTC的恶性程度及预后有一定意义。