Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations

In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

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.

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in early focal cerebral infarction following urokinase thrombolysis in rats

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.

Serum Matrix Metalloproteinase 3 and Tissue Inhibitor Metalloproteinase 1 in Vascular Dementia: A Comparative Study

Aim: To compare serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metallo-proteinase 1 (TIMP1) in vascular dementia patients and healthy control subjects. Methods: A case control study was carried out in Ain Shams University hospital, Cairo, Egypt. 32 cases with vascular dementia were collected and classified into 2 subgroups;vascular dementia of multiinfarct type (VDMI) 14 patients, and vascular dementia of subcortical type (VDSC) 18 subjects. 23 cases with normal cognitive functions were collected as control group. Cases were subjected to comprehensive geriatric assessment, neurological examination, neuropsychological testing and brain CT scan. Blood sample was collected to analyze serum level of matrix metalloproteinase 3 (MMP3) and tissue inhibitor metalloproteinase 1 (TIMP1). Results: Mean serum level of TIMP1 (20.85 × 103 picogram/ml) was significantly lower than mean serum level of TIMP1 in control group (27.69 × 103 picogram/ml) (p = 0.018). The same finding was also evident when comparing VDMI subgroup mean serum TIMP1 (18.71 × 103 pc/ml) to control group (p = 0.025). There was no significant difference between mean serum MMP3 levels in cases group (mean = 67.39 × 103) as compared to control group (mean = 61.65 × 103 pc/ml) (p = 0.519). Conclusion: Patients with VD particularly VDMI has lower serum level of TIMP1 as compared to control group.

Expressions of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in malignant peripheral nerve sheath tumor

BACKGROUND： Matrix metalloproteinase-9 （MMP-9） can degrade collagen IV （the main structural ingredient of basilar membrane）, and it also plays an important role in tumor vascularization, tumor cell progression, formation of metastatic focus, etc. Tissue inhibitor of metalloproteinase-1 （T1MP-1） can bind with MMP-9 to form 1 ： 1 compound and inhibit its activity, and can negatively regulate the tumor progression and metastasis. OBJECTIVE： To analyze the relationship of MMP-9 and T1MP-1 expressions with the pathological grade, metastasis and prognosis of malignant peripheral nerve sheath tumor （MPNST）. DESIGN： An observational comparative experiment. SETTING： Heze Medical College. PARTICIPANTS： Fifty-eight surgical pathological samples, which were clearly diagnosed to be MPNST, were collected from the pathological laboratory archives in the Department of Pathology, Heze Municipal Hospital from January 1988 to December 2003. The MPNST pathological types were common tumor in 53 cases, malignant triton tumor in 2 cases, epithelial MPNST in 2 cases and MPNST with gland differentiation in 1 case. The pathological grade was grade 1 in 11 cases, grade 2 in 24 cases and grade 3 in 23 cases. Besides, the resected tumor samples of 20 patients with benign peripheral nerve tumor （10 cases of nerve sheath tumor and 10 cases of neurofibromatosis） and the normal peripheral nerves （by-products of some surgeries） of 5 patients were also collected. The samples were used with the approval of the patients. Rat-anti-human MMP-9, TIMP-1 monoclonal antibody and S-P kit were purchased from Fuzhou Maixin Biotechnology, Co.,Ltd. METHODS： The documented paraffin blocks were again prepared to sections of 5 lJ m. The expressions of MMP-9 and TIMP-1 in the samples were detected with mmunohistochemical S-P method. The relationships of the MPNST severity, recurrence, metastasis and survival rate with the expressions of MMP-9 and TIMP-1 were analyzed. MAIN OUTCOME MEASURES： Relationships of MMP-9 and TIMP-1 expressions with the MPNST severity and prognosis. RESULTS： ①Expressions of MMP-9 and TIMP-1 in three tissues： MMP-9 and TIMP-1 stainings were mainly observed in cytoplasm. Among the 58 MPNST patients, the MMP-9 expression was significantly higher than those in normal peripheral nerve and benign tumor （P 〈 0.05）, while the TIMP-1 expression in MPNST was lower than those in normal peripheral nerve and benign tumor （P 〈 0.05）. ②Relationship of MMP-9 and TIMP-1 expressions with the severity and prognosis of MPNST： The expressions of both proteins were observed in the four subtypes. The positive expression of MMP-9 in the MPNST patients of grades 2 - 3 was significantly higher than that in the MPNST patients of grade 1 （P 〈 0.05）, while the expression of MMP-9 was significantly lower than that in the MPNST patients of grade 1 （P 〈 0.05）. The metastatic rate was positively correlated with MMP-9 expression （r =1.696, P 〈 0.05）, but negatively correlated with TIMP-1 expression （r = - 2.125, P 〈 0.05）. CONCLUSION： MMP-9 and TIMP-1 are associated with MPNST pathological grades and metastasis, and can be used as the indicators for judging the severity and orognosis of MPNST.

Modulation of Matrix Metalloproteinase and TIMP-1 Expression by TGF-β_1 in Cultured Human RPE Cells

In order to investigate the effects of TGF-β1 on the expression of MMP-2, -9 and TIMP- 1 in human retinal pigment epithelial （RPE） cells, the third-sixth passage cultured RPE cells were treated with TGF-β1 at different concentrations （0.01, 0. 1, 1.0, 10 ng/mL）, the expression of MMP-2, -9 and TIMP-1 mRNA was detected by semi-qudntitative RT-PCR assays. MMP-2, -9 and TIMP-1 mRNA were expressed in the cultured RPE cells. The values of MMP-2/β-actin in the cells treated with 0.1, 1.0, 10 ng/mL TGF-β1 were 1.04±0.04, 1.07±0.02 and 1.11±0.03, respectively, significantly higher than in the control group （0.96±0.03, P〈0. 05-0.01）. The expression of MMP-2 mRNA could be up-regulated by TGF-β, , in a dose-dependent manner. The expression of MMP-9 mRNA in the cultured RPE cells was slightly up-regulated by various TGF-β1 concentrations treatment. The values of TIMP-1/β-actin in the cells treated with 0.01 and 0.1 ng/ mL TGF-β1 were 0.85 ±0.01 and 0.97 ± 0.02 respectively, significantly lower than in the control group （1.07±0.04, P〈0.01）, indicating that the expression of TIMP-1 mRNA was down-regulated by TGF-β1 at low concentrations. But along with the increase of TGF-β1 concentrations （1.0 and 10 ng/mL）, the expression of TIMP-1 mRNA was slightly up-regulated, not significantly different from that in the control group （P〉0.05）. It was concluded that TGF-β1 might play an important role in the up-regulation of the expression of MMP-2 in RPE cells and result in a directional shift in the balance between MMP and TIMP. This may be facilitated for RPE cells to migrate in the pathogenesis of vitreoretinopathy.

虎黄烧伤搽剂联合常规疗法治疗Wagner 1-2级糖尿病足临床观察

目的探讨虎黄烧伤搽剂联合常规疗法治疗Wagner 1-2级糖尿病足的临床疗效。方法选取重庆医科大学附属大足医院2022年1月至2023年6月收治的Wagner 1-2级糖尿病足患者94例,按随机数字表法分为对照组和观察组,各47例。两组患者均予常规降糖药物,并以蚕食清创法清除坏死组织;观察组患者加用虎黄烧伤搽剂治疗。两组均连续治疗28 d。结果观察组疗效优于对照组(P<0.05);观察组糖尿病足感染率为2.13%,显著低于对照组的14.89%(P<0.05)。与对照组比较,观察组患者治疗第7,14,28天创面面积显著缩小,创面愈合时间显著缩短,创面组织中血管内皮生长因子(VEGF)、表皮生长因子(EGF)、基质金属蛋白酶抑制剂-1(TIMP-1)、转化生长因子-β(TGF-β)水平均显著升高,基质金属蛋白酶-9(MMP-9)水平显著降低(P<0.05)。结论虎黄烧伤搽剂联合常规疗法治疗Wagner 1-2级糖尿病足,可进一步上调创面组织中VEGF,EGF,TIMP-1,TGF-β水平,降低MMP-9水平,加速创面愈合。

乳腺癌组织中TIMP-3及DNMT1的表达与患者预后的相关性

目的:分析研究乳腺癌患者中基质金属蛋白酶组织抑制因子3(TIMP-3)及DNA甲基转移酶1(DNMT1)的表达水平与患者临床预后的相关性。方法:收集58例临床资料完整的乳腺癌手术切除标本,采用免疫组化SP法检测癌组织及相应癌旁组织中TIMP-3、DNMT1、ER、PR、HER-2、p53、Ki-67的表达,将TIMP-3、DNMT1表达水平与临床病理参数及随访生存状况进行相关性分析,所有入组患者均进行随访5年以上。结果:我们发现,在乳腺癌组织中,TIMP-3呈低表达,DNMT1呈高表达,TIMP-3及DNMT1的表达呈负相关;TIMP-3表达水平与Ki-67呈负相关,DNMT1表达水平与Ki-67呈正相关,与其他临床病理参数未见相关性。Cox风险比例模型分析显示只有临床分期和DNMT1表达水平是影响总生存期(OS)和无病生存期(DFS)的独立风险因素。TIMP-3低表达组的5年OS和DFS均显著低于高表达组,DNMT1高表达组的5年OS和DFS均显著低于低表达组。结论:研究表明乳腺癌中TIMP-3及DNMT1表达水平与肿瘤细胞恶性表型及患者生存时间有关,可能成为判断乳腺癌预后的一项重要指标,并作为治疗计划制定的依据。

血清TLR4、TIMP-1水平与小儿热性惊厥临床特征的关系及对继发癫痫的预测价值

目的分析血清Toll样受体4(TLR4)、基质金属蛋白酶组织抑制剂(TIMP)-1水平与小儿热性惊厥(FC)临床特征的关系及对FC继发癫痫的预测价值。方法选取2019年1月至2022年6月320例FC患儿作为研究组,另选取同期发热无惊厥儿童150例作为发热组,体检健康儿童150例作为对照组。根据FC患儿是否继发癫痫分为癫痫组和无癫痫组。采用酶联免疫吸附试验检测血清TLR4、TIMP-1水平,采用Pearson相关分析TLR4、TIMP-1水平及与临床指标间的相关性。采用受试者工作特征(ROC)曲线分析血清TLR4、TIMP-1预测FC继发癫痫的价值。采用Logistic回归分析FC患儿继发癫痫的影响因素。结果FC患儿、发热无惊厥儿童、体检健康儿童血清TLR4、TIMP-1水平依次降低,且两两比较,差异均有统计学意义(P<0.05)。研究组与发热组围生期异常发生情况、肿瘤坏死因子α(TNF-α)、C-反应蛋白(CRP)、白细胞介素-1β(IL-1β)水平和振幅整合脑电图(AEEG)评分比较,差异均有统计学意义(P<0.05)。癫痫组患儿血清TLR4、TIMP-1水平明显高于无癫痫组(P<0.05)。癫痫组和无癫痫组患儿首次惊厥次数、惊厥持续时间、首次惊厥前发热时间、围生期异常发生情况、TNF-α、CRP、IL-1β水平和AEEG评分比较,差异均有统计学意义(P<0.05)。血清TLR4水平与TIMP-1呈正相关(P<0.05);血清TLR4、TIMP-1水平与TNF-α、CRP、IL-1β呈正相关(P<0.05),与AEEG评分呈负相关(P<0.05)。TLR4、TIMP-1联合预测FC患儿继发癫痫的曲线下面积(AUC)明显高于单项检测的AUC(Z_(TLR4-联合)=3.016,P=0.003;Z_(TIMP-1-联合)=2.232,P=0.026)。Logistic回归分析结果表明,TLR4、TIMP-1、TNF-α、CRP、IL-1β水平升高,AEEG评分降低均为FC继发癫痫的危险因素(P<0.05)。结论血清TLR4、TIMP-1与FC患儿临床特征密切相关,TLR4、TIMP-1可能是FC继发癫痫的影响因素。

多西他赛联合PD-1抑制剂对晚期非小细胞肺癌预后及血清MMP-9、TIMP-1水平的影响

目的探讨多西他赛联合程序性死亡受体1(PD-1)抑制剂对晚期非小细胞肺癌(NSCLC)预后及血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-1(TIMP-1)水平的影响。方法将90例晚期NSCLC患者随机分为研究组和对照组,每组45例。对照组给予多西他赛和顺铂治疗,研究组在对照组治疗基础上给予PD-1治疗,3周为1个治疗周期,共治疗6个周期。比较2组治疗后客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)、总生存期(OS),观察2组治疗期间不良反应发生情况及治疗前后血清MMP-9、TIMP-1水平的变化。结果研究组治疗后DCR、PFS、OS显著高于对照组(P<0.05);治疗期间2组不良反应发生率比较差异无统计学意义(P>0.05);2组治疗后血清MMP-9、TIMP-1水平较治疗前显著降低(P<0.05),且研究组降低较对照组更为显著(P<0.05)。结论多西他赛联合PD-1抑制剂对晚期NSCLC具有较好的疗效和预后,能够降低血清MMP-9、TIMP-1水平,降低肺癌细胞侵袭转移的能力,安全性良好。

Increased expression of matrix metalloproteinase-9 associated with gastric ulcer recurrence

AIM: To compare matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in gastric ulcer (GU) and chronic superficial gastritis (CSG). METHODS: This study enrolled 63 patients with GU and 25 patients with CSG. During upper gastroduodenal endoscopy, we took samples of gastric mucosa from the antrum and ulcer site from patients with GU, and samples of antral mucosa from patients with CSG. Mucosal biopsy tissues were cultured for 24 h, and the culture supernatant was measured for levels of MMP-9 and TIMP-1. After receiving eradication therapy for Helicobacter pylori (H. pylori ) and 8 wk proton-pump inhibitor therapy for GU, follow-up endoscopy examination was performed after 6 mo and whenever severe symptoms occurred. RESULTS: Levels of MMP-9 and TIMP-1 at the ulcer site or in the antrum were significantly higher in GU than CSG patients. MMP-9 levels at the ulcer site were significantly higher than in the antrum in GU patients, and had a significantly positive correlation with TIMP-1. MMP-9 levels were significantly higher in H. pylori -positive than H. pylori -negative GU and CSG patients. Levels of MMP-9 or TIMP-1 at the ulcer site were associated with the histological severity of activity and inflammation. About 57 GU patients were followed up, and seven had GU recurrence. H. pyloriinfection and MMP-9 levels were risk factors for the recurrence of GU adjusted for age and sex by multiple logistic regression analysis. CONCLUSION: MMP-9 may perform an important function in gastric ulcer formation and recurrence.

电针对负透镜诱导型近视豚鼠视网膜中MMP-3和TIMP-3及Col3α1表达的影响

目的:探讨电针对负透镜诱导型近视豚鼠视网膜中基质金属蛋白酶(MMP)-3、金属蛋白酶组织抑制剂(TIMP)-3和III型胶原α1(Col3α1)表达的影响。方法:将80只豚鼠随机分为正常对照组、负透镜诱导型近视组、电针干预组和假穴组,每组20只。正常对照组不做任何干预,负透镜诱导型近视组、电针干预组和假穴组,右眼均配戴-6.0 D透镜,左眼不戴镜。戴镜同时电针干预组在合谷穴与太阳穴给予电针刺激,假穴组豚鼠在假穴位进行干预。造模前,造模2、4 wk检影验光检测屈光度,A超检测眼轴长度,HE染色观察视网膜组织结构变化,定量聚合酶链反应(Q-PCR)和蛋白免疫印迹(WB)检测视网膜中MMP-3、TIMP-3、Col3α1 mRNA和蛋白表达的情况。结果:造模2、4 wk,负透镜诱导型近视组与正常对照组相比眼轴长度均明显增加(均P<0.05),屈光度均明显降低(均P<0.05);与负透镜诱导型近视组相比,电针干预组干预后眼轴长度均减少(均P<0.05),屈光度均增加(均P<0.05)。HE染色显示,正常对照组豚鼠视网膜组织各层分界明显,排列规则;负透镜诱导型近视组视网膜厚度、内外核层厚度及细胞数量减少,排列不规则;电针干预组视网膜整体结构较为完善,排列较规则,组织各层形态结构未出现明显异常。Q-PCR和WB检测结果显示,负透镜诱导型近视组视网膜中MMP-3、TIMP-3和Col3α1 mRNA及蛋白表达均比正常对照组明显升高(均P<0.05);而电针干预组干预后视网膜中MMP-3、TIMP-3和Col3α1mRNA及蛋白表达均较负透镜诱导型近视组明显降低(均P<0.05)。结论:电针能够延缓负透镜诱导型近视豚鼠眼轴增长,下调负透镜诱导型近视豚鼠视网膜中的MMP-3、TIMP-3及Col3α1 mRNA及蛋白表达。

Diabetes-related intestinal region-specific thickening of ganglionic basement membrane and regionally decreased matrix metalloproteinase 9 expression in myenteric ganglia

BACKGROUND The importance of the neuronal microenvironment has been recently highlighted in gut region-specific diabetic enteric neuropathy. Regionally distinct thickening of endothelial basement membrane(BM) of intestinal capillaries supplying the myenteric ganglia coincide with neuronal damage in different intestinal segments. Accelerated synthesis of matrix molecules and reduced degradation of matrix components may also contribute to the imbalance of extracellular matrix dynamics resulting in BM thickening. Among the matrix degrading proteinases, matrix metalloproteinase 9(MMP9) and its tissue inhibitor(TIMP1) are essential in regulating extracellular matrix remodelling.AIM To evaluate the intestinal segment-specific effects of diabetes and insulin replacement on ganglionic BM thickness, MMP9 and TIMP1 expression.METHODS Ten weeks after the onset of hyperglycaemia gut segments were taken from the duodenum and ileum of streptozotocin-induced diabetic, insulin-treated diabetic and sex-and age-matched control rats. The thickness of BM surrounding myenteric ganglia was measured by electron microscopic morphometry. Wholemount preparations of myenteric plexus were prepared from the different gut regions for MMP9/TIMP1 double-labelling fluorescent immunohistochemistry. Post-embedding immunogold electron microscopy was applied on ultrathin sections to evaluate the MMP9 and TIMP1 expression in myenteric ganglia and their microenvironment from different gut segments and conditions. The MMP9 and TIMP1 messenger ribonucleic acid(m RNA) level was measured by quantitative polymerase chain reaction.RESULTS Ten weeks after the onset of hyperglycaemia, the ganglionic BM was significantly thickened in the diabetic ileum, while it remained intact in the duodenum. The immediate insulin treatment prevented the diabetes-related thickening of the BM surrounding the ileal myenteric ganglia. Quantification of particle density showed an increasing tendency for MMP9 and a decreasing tendency for TIMP1 from the proximal to the distal small intestine under control conditions. In the diabetic ileum, the number of MMP9-indicating gold particles decreased in myenteric ganglia, endothelial cells of capillaries and intestinal smooth muscle cells, however, it remained unchanged in all duodenal compartments. The MMP9/TIMP1 ratio was also decreased in ileal ganglia only. However, a marked segment-specific induction was revealed in MMP9 and TIMP1 at the m RNA levels.CONCLUSION These findings support that the regional decrease in MMP9 expression in myenteric ganglia and their microenvironment may contribute to extracellular matrix accumulation, resulting in a region-specific thickening of ganglionic BM.

脑脊液基质金属蛋白酶9水平和基质金属蛋白酶9/基质金属蛋白酶组织抑制剂1比值与结核性脑膜炎病情严重程度的相关性及对预后的预测价值研究

目的 探讨脑脊液基质金属蛋白酶9(MMP-9)水平和MMP-9/基质金属蛋白酶组织抑制剂1(TIMP-1)比值与结核性脑膜炎病情严重程度的相关性及对预后的预测价值。方法 选择2021年1月至2023年2月在湖南省胸科医院住院的结核性脑膜炎患者72例为观察组,以同期住院的非肿瘤非感染性头痛患者52例为对照组。比较2组患者脑脊液MMP-9水平和MMP-9/TIMP-1比值。根据改良的英国医学研究理事会结核性脑膜炎分期标准将观察组患者分为Ⅰ期组、Ⅱ期组、Ⅲ期组,比较3组患者MMP-9水平和MMP-9/TIMP-1比值。根据预后情况将观察组患者分为预后良好组和预后不良组,比较2组MMP-9水平和MMP-9/TIMP-1比值,并以受试者工作特征(ROC)曲线法评估各指标对结核性脑膜炎的预后预测价值。结果 观察组MMP-9水平及MMP-9/TIMP-1比值均大于对照组[(96±21)μg/L比(50±12)μg/L、(1.21±0.33)比(0.67±0.15)](均P<0.05),但2组间TIMP-1水平比较差异无统计学意义(P>0.05)。不同严重程度结核性脑膜炎患者MMP-9水平及MMP-9/TIMP-1比值差异均有统计学意义,且均呈Ⅰ期<Ⅱ期<Ⅲ期(均P<0.05);不同严重程度结核性脑膜炎患者TIMP-1水平差异均无统计学意义(均P>0.05)。相关性分析结果显示,结核性脑膜炎病情严重程度与MMP-9水平及MMP-9/TIMP-1比值均呈正相关(r=0.861、P=0.012;r=0.731、P=0.008),与TIMP-1无相关性(r=0.220,P=0.063)。预后不良组患者MMP-9水平及MMP-9/TIMP-1比值均高于预后良好组(均P<0.05),2组TIMP-1水平差异无统计学意义(P>0.05)。ROC曲线分析结果显示,MMP-9水平、MMP-9/TIMP-1比值预测结核性脑膜炎患者预后不良的截断值分别为112.04μg/L、1.41,曲线下面积分别为0.803、0.905(均P<0.05)。结论 结核性脑膜炎患者脑脊液MMP-9水平、MMP-9/TIMP-1比值明显升高,且MMP-9水平、MMP-9/TIMP-1比值与结核性脑膜炎的病情严重程度呈正相关,并可用于预测患者预后。

骨髓增殖性肿瘤患者血清金属蛋白酶抑制剂-1、基质金属蛋白酶-9、血管内皮生长因子与骨髓纤维化程度的相关性

目的探讨骨髓增殖性肿瘤(MPN)患者血清血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)及金属蛋白酶抑制剂-1(TIMP-1)与骨髓纤维化(MF)分级的关系。方法选择90例费城染色体阴性(Ph-)MPN初诊患者为MPN组。根据世界卫生组织(WHO)2016年骨髓纤维化分级标准将MPN患者分为纤维化前期或早期组54例和明显纤维化期组36例;另选取健康志愿者50例作为对照组。采用酶联免疫吸附实验检测血清VEGF、MMP-9、TIMP-1水平并计算TIMP-1与MMP-9比值(TIMP-1/MMP-9)。采用Spearman秩相关检验分析VEGF、MMP-9、TIMP-1、TIMP-1/MMP-9与MF分级的相关性。绘制受试者工作特征(ROC)曲线分析各指标单独或联合诊断MPN或区分MF分级的预测价值。结果与对照组相比,MPN组血清VEGF、MMP-9和TIMP-1均升高,差异有统计学意义(P<0,05)。VEGF、MMP-9、TIMP-1、TIMP-1/MMP-9诊断MPN的曲线下面积(AUC)分别为0.834、0.745、0.923、0.618;VEGF、MMP-9和TIMP-1联合诊断MPN的AUC为0.960;当最佳截断值为0.627时,敏感度为85.56%,特异度为92.00%。与纤维化前期或早期组相比,明显纤维化期组患者血清VEGF、TIMP-1、TIMP-1/MMP-9均升高,差异有统计学意义(P<0.05)。Spearman相关性分析结果显示,VEGF(r=0.378,P=0.001)、TIMP-1(r=0.512,P<0.001)、TIMP-1/MMP-9(r=0.353,P=0.001)与MPN患者MF分级呈正相关(P<0.05)。ROC曲线分析显示,VEGF、MMP-9、TIMP-1、TIMP-1/MMP-9区分纤维化前期或早期患者和明显纤维化期患者的AUC分别为0.723、0.523、0.802、0.708;VEGF、TIMP-1和TIMP-1/MMP-9联合区分纤维化前期或早期患者和明显纤维化期患者的AUC为0.838;当最佳截断值为0.530时,敏感度为72.22%,特异度为85.19%。结论血清VEGF、TIMP-1和TIMP-1/MMP-9均可反映MPN患者MF进展,各指标联合检测可预测MPN患者MF程度。

CTA联合血清MMP-9、TIMP-1对脑梗死患者颈动脉斑块诊断价值

目的探究计算机断层扫描血管成像(CTA)联合血清基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂-1(TIMP-1)对脑梗死患者颈动脉斑块诊断价值。方法选取2021年5月-2021年12月期间我院神经内科收治的140例脑梗死患者作为试验组研究对象,另选择同期至我院进行体检的健康者80例作为参照组。试验组患者均行CTA和数字减影血管造影(DSA),分析CTA诊断颈动脉斑块价值。试验组和参照组均接受血清MMF-9 TIMP-1检测。对比试验组与参照组的血清MMP-9、TIMP-1水平差异。在试验组中,以DSA为金标准,将患者分为斑块组和无斑块组,对比两组之间的血清MMP-9、TIMP-1水平差异,对CTA联合血清MMP-9、TIMP-1诊断颈动脉斑块的效果进行受试者特征曲线(ROC)分析。结果CTA检测结果显示存在颈动脉斑块者64例,无斑块组76例,CTA诊断颈动脉斑块敏感度为96.88%,特异性为97.37%,准确度为97.14%;试验组血清MMP-9水平显著高于参照组(P<0.05),TIMP-1水平显著低于参照组(P<0.05);斑块组血清MMP-9水平显著高于无斑块组(P<0.05),TIMP-1水平显著低于无斑块组(P<0.05);ROC曲线显示血清CTA、MMP-9、TIMP-1水平单独及联合诊断颈动脉斑块AUC值依次为0.979、0.835、0.812和0.993。结论CTA联合血清MMP-9、TIMP-1对脑梗死患者颈动脉斑块具有良好的诊断价值。

CTA联合血清MMP-9、TIMP-1在缺血性脑卒中诊断中的应用

目的 探究CT血管成像(CTA)联合血清基质金属蛋白酶9(MMP-9)、金属蛋白酶组织抑制因子1(TIMP-1)在缺血性脑卒中诊断中的应用。方法 选取2021年5月至2022年5月期间张家口市第一医院神经内科收治的140例脑卒中患者作为研究组研究对象,均行CTA检查,以数字血管造影(DSA)为金标准,分析CTA对缺血性脑卒中诊断价值,另选择同期至此院进行体检的健康者80名作为对照组,比较两组患者血清MMP-9、TIMP-1水平。结果 140例患者,共检查463条头颈血管,经CTA诊断无狭窄236条、轻度狭窄66条、中度狭窄36条、重度狭窄46条、闭塞22条,与DSA对照CTA诊断缺血性脑卒中患者血管狭窄程度的灵敏度为81.25%,特异度为90.15%;CTA诊断轻度狭窄患者74例、中度16例、重度46、闭塞4例,与DSA对照CTA诊断灵敏度82.50%、特异度83.33%;研究组患者血清MMP-9、TIMP-1表达水平均显著高于对照组患者,差异有统计学意义(t=73.668、33.925,P<0.05),且研究组患者随着狭窄程度增加,血清MMP-9、TIMP-1水平逐渐上升,差异有统计学意义(F=13298.37、901.001,P<0.05);MMP-9以247.14 ng/mL为临界值,阳性53例,阴性87例;TIMP-1均值(239.21 ng/mL)为临界值,阳性53例,阴性87例;以CTA阳性为基础,MMP-9、TIMP-1任一指标阳性则定义为联合诊断阳性,结果显示联合诊断灵敏度为88.75%,特异度为80.00%。结论 CTA联合血清MMP-9、TIMP-1对缺血性脑卒中诊断效能较高,临床应在密切观察缺血性脑卒中患者CTA检查基础上联合MMP-9、TIMP-1水平检测。

Atorvastatin reduces myocardial fibrosis in a rat model with post- myocardial infarction heart failure by increasing the matrix metaHoproteinase-2/tissue matrix metalloproteinase inhibitor-2 ratio

Background The cholesterol-lowering statin drugs have some non-lipid-lowering effects, such as inhibiting myocardial remodeling. However, the underlying mechanism is still unclear. Methods The left anterior descending coronary artery was ligated to establish a rat model of heart failure, and the rats were divided into a sham operation （SO） group, myocardial infarction model （MI） group, and MI-atorvastatin group. Changes in hemodynamic parameters were recorded after the final drug administration. Histological diagnosis was made by reviewing hematoxylin and eosin （HE） stained tissue. Real-time quantitative polymerase chain reaction （PCR） was performed to determine the expressions of type I and type III collagen, matrix metalloproteinase-2 （MMP-2）, and tissue matrix metalloproteinase inhibitor-2 （TIMP-2）. Further, primary rat cardiac fibroblasts were cultured and the MTT assay was performed to determine the effect of atorvastatin on cardiac fibroblast proliferation. Results The model of heart failure was established and the results of HE staining and Masson＇s trichrome staining revealed that the rats in the heart failure group showed obvious hyperplasia of fibrotic tissue, which was significantly reduced in the atorvastatin group. Real-time quantitative PCR showed that the MI group showed a significantly increased expression of type I and type III coltagen, MMP-2, and TIMP-2, but a significantly reduced MMP-2/T＇IMP- 2 ratio. Compared with the MI group, the atorvastatin group showed significantly reduced expression of type I and III collagen, unchanged expression of MMP-2, significantly reduced expression of TIMP-2, and an increased MMP-2/ TIMP-2 ratio. We further found that atorvastatin significantly inhibited the Ang II-induced fibroblast proliferation and the expression of type I and type III collagen in cardiac fibroblasts while increasing the MMP-2/TIMP-2 ratio. Conclusions These data suggest that atorvastatin can inhibit cardiac fibroblast proliferation and enhance collagen degradation by increasing the MMP-2/TIMP-2 ratio, thereby inhibiting the formation of myocardial fibrosis in rats with heart failure after myocardial infarction.

Effects of Saikosaponin-D on syndecan-2,matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 in rats with hepatocellular carcinoma

OBJECTIVE:To investigate effects of Saikosaponin D(SSd) on syndecan-2,matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases-2(TIMP-2) in livers of rat with hepatocellular carcinoma(HCC).METHODS:Male SD rats were divided into control(n=10),model(n=20) and SSd(n=20) groups,and model and SSd groups given intragastric 0.2%(w/v) N-diethylnitrosamine to induce HCC.SSd group received 0.03%(w/v) SSd in saline.Liver samples were analysed immunohistochemically for syndecan-2,MMP-2,MMP-13 and TIMP-2 at 16 weeks.RESULTS:The model group had more malignant nodules than the SSd group;all model-group HCC cells were grade III;SSd-group HCC cells were grades I-II.Controls showed normal hepatic cell phenotypes and no syndecan-2 + staining.Syndecan-2 + staining was greater in the model group(35.2%,P≤0.001) than in controls or the SSd group(16.5%,P ≤ 0.001).The model group had more intense MMP-2 + staining than controls(0.37 vs 0.27,P≤0.01) or the SSd group(0.31 vs 0.37,P≤0.05);and higher MMP-13 + staining(72.55%) than in controls(12.55%,P≤0.001) and SSd group(20.18%,P≤0.01).The model group also had more TIMP-2 + staining(57.2%) than controls(20.9%,P≤0.001) and SSd group(22.7%,P≤0.001).Controls and SSd group showed no difference in TIMP-2 + rates.CONCLUSION:SSd inhibited HCC development,and downregulated expression of syndecan-2,MMP-2,MMP-13 and TIMP-2 in rat HCC liver tissue.