Expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in brain tissue of diabetic rats with ischemia reperfusion

Objective: To discuss the expression and significance of angiostatin, vascular endothelial growth factor and matrix metalloproteinase-9 in the brain tissue of diabetic rats with ischemia reperfusion. Methods: A total of 60 male Wistar rats were randomly divided into the normal group, sham group, diabetic cerebral infarction group and single cerebral infarction group according to the random number table, with 15 rats in each group. The high sucrose diet and intraperitoneal injection of streptozotocin were performed for the modeling of diabetic rats, while the thread-occlusion method was employed to build the model of cerebral ischemia reperfusion. The immunohistochemical staining was performed to detect the expression of angiostatin, vascular endothelial growth factor(VEGF) and matrix metalloproteinase-9(MMP-9) in the brain tissue. Results: The expression of angiostatin after the reperfusion in the brain tissue of rats in the single cerebral infarction group and diabetic cerebral infarction group was increased 6 h after the reperfusion, reached to the peak on 1 d and then decreased gradually. The expression of angiostatin in the diabetic cerebral infarction group 6 h, 1 d, 3 d and 7 d after the reperfusion was significantly higher than that in the single cerebral infarction group(P<0.05). VEGF began to be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak at 6 h and then decreased gradually. The expression of VEGF in the diabetic cerebral infarction group at each time point after the reperfusion was significantly lower than that in the single cerebral infarction group(P<0.05). MMP-9 began to be be increased 1 h after the reperfusion in the single cerebral infarction group and diabetic cerebral infarction group, reached to the peak on 1 d and then decreased gradually. The expression of MMP-9 in the diabetic cerebral infarction group at each time point after the reperfusion was significantly higher than that in the single cerebral infarction group(P<0.05). Conclusions: The high glucose environment in which the diabetic cerebral infarction is occurred is to induce the formation of MMP-9 at first and then activate and increase the expression of angiostatin. Afterwards, the expression of VEGF is inhibited, resulting in the poor angiogenesis after cerebral infarction, which thus makes the injury of brain tissue after cerebral infarction even worse than the non-diabetes mellitus.

Local inhibition of matrix metalloproteinases reduced M2 macrophage activity and impeded recovery in spinal cord transected rats after treatment with fibroblast growth factor-1 and nerve grafts

Alternatively activated macrophages （M2 macrophages） promote central nervous system regeneration. Our previous study demonstrated that treatment with peripheral nerve grafts and fibroblast growth factor-1 recruited more M2 macrophages and improved partial functional recovery in spinal cord transected rats. The migration of macrophages is matrix metalloproteinase （MMP） dependent. We used a general inhibitor of MMPs to influence macrophage migration, and we examined the migration of macrophage populations and changes in spinal function. Rat spinal cords were completely transected at Ts, and 5 mm of spinal cord was removed （group T）. In group R, spinal cord-transected rats received treatment with fibroblast grow th factor- 1 and peripheral nerve grafts. In group RG, rats received the same treatment as group R with the addition of 200 μM GM6001 （an MMP inhibitor） to the fibrin mix. We found that MMP-9, but not MMP- 2, was upregulated in the graft area of rats in group R. Local application of the MMP inhibitor resulted in a reduction in the ratio of arginase-1 （M2 macrophage subset）/inducible nitric oxide synthase-postive cells. When the MMP inhibitor was applied at 8 weeks postoperation, the partial functional recovery observed in group R was lost. This effect was accompanied by a decrease in brain-derived neurotrophic factor levels in the nerve graft. These results suggested that the arginase-1 positive population in spinal cord transected rats is a migratory cell population rather than the phenotypic conversion of early iNOS^＋ cells and that the migration of the arginase-1^＋ population could be regulated locally. Simultaneous application of MMP in- hibitors or promotion of MMP activity for spinal cord injury needs to be considered if the coadministered treatment involves M2 recruitment.

Methanol extract of Codium fragile inhibits tumor necrosis factor-ɑ-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation

Objective:To evaluate whether the methanol extract of Codium fragile(MECF) regulates tumor necrosis factor-α(TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9(MMP-9).Methods:Reverse transcriptionpolymerase chain reaction(RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB(NF-κB) subunits,p65 and p50,and IκB in MDA-MB-231 cells.3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT) assay was used for cell viability.MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay,respectively.NF- κB activity was measured by an electrophoretic mobility shift assay and luciferase activity.Results:MECF had no effects on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α.MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control,whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells.Additionally,zymography,western blot analysis,and reverse transcriptase-polymerase chain reaction(RT-PCR) confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion.According to an electrophoretic morbidity shift assay,pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of nuclear factor- κB(NF- κB),which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9.Furthermore,treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment.The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF- κB luciferase activity.Conclusion:MECF exhibited its antiinvasive capability by downregulating TNF-α-induced MMP-9 expression,resulting from the suppression of NF- κB activity in the human breast cancer cell line MDA-MB-231.

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.

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.

The interaction between epidermal growth factor (EGF) and matrix metalloproteinase induces the development of sweat glands in human fetal skin

Objective:The development of sweat glands is a very complicated biological process involving many factors. In this study, we explore the inter-relationship between epidermal growth factor (EGF), matrix metalloproteinases (MMP-2,MMP-7) and development of sweat glands in human embryos. Furthermore, we hope to elucidate the mechanism(s) underlying the induction of epidermal stem cells into sweat gland cells.

Insulin-like growth factor binding protein related protein 1 knockdown attenuates hepatic ?brosis via the regulation of MMPs/TIMPs in mice

Background: Previous research suggested that insulin-like growth factor binding protein related protein 1(IGFBPrP1), as a novel mediator, contributes to hepatic fibrogenesis. Matrix metalloproteinases(MMP) and tissue inhibitors of metalloproteinases(TIMP) play an essential role in hepatic fibrogenesis by regulating homeostasis and remodeling of the extracellular matrix(ECM). However, the interaction between IGFBPrP1 and MMP/TIMP is not clear. The present study was to knockdown IGFBPrP1 to investigate the correlation between IGFBPrP1 and MMP/TIMP in hepatic fibrosis. Methods: Hepatic fibrosis was induced by thioacetamide(TAA) in mice. Knockdown of IGFBPrP1 expression by ultrasound-targeted microbubble destruction-mediated CMB-shRNA-IGFBPrP1 delivery, or inhibition of the Hedgehog(Hh) pathway by cyclopamine treatment, was performed in TAA-induced liver fibrosis mice. Hepatic fibrosis was determined by hematoxylin and eosin and Sirius red staining. Hepatic expression of IGFBPrP1, α-smooth muscle actin( α-SMA), transforming growth factor β 1(TGF β1), collagen I, MMPs/TIMPs, Sonic Hedgehog(Shh), and glioblastoma family transcription factors(Gli1) were investigated by immunohistochemical staining and Western blotting analysis. Results: We found that hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I were increased longitudinally in mice with TAA-induced hepatic fibrosis, concomitant with MMP2/TIMP2 and MMP9/TIMP1 imbalance and Hh pathway activation. Knockdown of IGFBPrP1 expression, or inhibition of the Hh pathway, reduced the hepatic expression of IGFBPrP1, TGF β1, α-SMA, and collagen I and re-established MMP2/TIMP2 and MMP9/TIMP1 balance. Conclusions: Our findings suggest that IGFBPrP1 knockdown attenuates liver fibrosis by re-establishing MMP2/TIMP2 and MMP9/TIMP1 balance, concomitant with the inhibition of hepatic stellate cell activation, down-regulation of TGF β1 expression, and degradation of the ECM. Furthermore, the Hh pathway mediates IGFBPrP1 knockdown-induced attenuation of hepatic fibrosis through the regulation of MMPs/TIMPs balance.

Interaction between insulin-like growth factor binding protein-related protein 1 and transforming growth factor beta 1 in primary hepatic stellate cells

BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.

血清缺氧诱导因子-1α、内皮素-1及基质金属蛋白酶-9联合检测对颅内动脉瘤破裂出血142例手术预后的价值

目的探讨血清缺氧诱导因子-1α(HIF-1α)、内皮素-1(ET-1)、基质金属蛋白酶-9(MMP-9)联合预测颅内动脉瘤破裂出血术后预后不良的价值。方法选取2020年1月至2022年1月东台市人民医院收治的颅内动脉瘤破裂出血病人142例作为研究组,另选取同期健康体检者140例作为对照组,检测病人术前、入院1周(均为术后)、术后6个月血清HIF-1α、ET-1、MMP-9水平并进行比较。另依据病人出院6个月后预后情况,将其分为预后良好组(101例)和预后不良组(41例),对比预后良好组和预后不良组术前、入院1周、术后6个月血清HIF-1α、ET-1、MMP-9水平,分析颅内动脉瘤破裂出血病人预后不良的影响因素及血清HIF-1α、ET-1、MMP-9单项及联合检测对颅内动脉瘤破裂出血病人预后不良的预测价值。结果研究组术前血清HIF-1α、ET-1、MMP-9水平均高于对照组(P<0.05);研究组随访6个月预后不良发生率为28.87%(41/142),血清HIF-1α、ET-1、MMP-9水平经重复测量方差分析差异有统计学意义(P<0.05),预后不良组入院1周、术后6个月血清HIF-1α(42.43±3.05)μg/L和(41.53±4.52)μg/L、ET-1(14.27±1.24)ng/L和(13.96±2.04)ng/L、MMP-9(15.57±1.81)μg/L和(14.68±2.65)μg/L均低于术前(51.19±4.38)μg/L、(16.50±1.45)ng/L、(18.26±2.29)μg/L;预后良好组入院1周、术后6个月血清HIF-1α(40.78±1.53)μg/L和(34.87±4.68)μg/L、ET-1(13.12±2.16)ng/L和(10.05±1.96)ng/L、MMP-9(14.87±1.20)μg/L和(12.21±2.87)μg/L均低于术前(47.82±4.13)μg/L、(14.89±2.75)ng/L、(17.41±1.21)μg/L;预后良好组术后6个月血清HIF-1α、ET-1、MMP-9水平均低于入院1周(P<0.05)。预后不良组术前、入院1周、术后6个月血清HIF-1α、ET-1、MMP-9水平均高于预后良好组(P<0.05)。预后不良组多发动脉瘤、脑积水、Hunt-Hess分级Ⅳ~Ⅴ级、CT Fisher分级3~4级、手术时机为≥72 h、并发脑血管痉挛、并发脑梗死病人占比均高于预后良好组(P<0.05);Hunt-Hess分级Ⅳ~Ⅴ级、手术时机为≥72 h、术前及入院1周血清HIF-1α、ET-1、MMP-9高水平均是颅内动脉瘤破裂出血预后不良的危险因素(P<0.05);受试者操作特征曲线显示,术前及入院1周血清HIF-1α、ET-1、MMP-9三者联合预测颅内动脉瘤破裂出血病人预后不良的灵敏度(97.56%、95.12%)和曲线下面积(0.93、0.91)高于单独预测(P<0.05),特异度与单独评估比较差异无统计学意义(P>0.05)。结论颅内动脉瘤破裂出血病人术前血清HIF-1α、ET-1、MMP-9水平均高于健康人群,术前和入院1周血清HIF-1α、ET-1、MMP-9高水平均是术后预后不良的独立危险因素,且对颅内动脉瘤破裂出血术后预后不良具有一定预测价值,但三者联合预测价值更高。

信迪利单抗联合贝伐珠单抗治疗不可切除肝细胞肝癌患者效果及其血清VEGF、MMP-9水平变化

目的 探讨信迪利单抗联合贝伐珠单抗治疗不可切除肝细胞肝癌患者效果及其血清血管内皮生长因子(VEGF)、基质金属蛋白酶-9(MMP-9)水平变化。方法 选取2021年1月至2022年12月在周口市中心医院确诊的80例不可切除肝细胞肝癌患者,根据患者治疗方式将患者分为单抗联合组和对照组。对照组患者接受口服甲苯磺酸索拉非尼治疗,纳入36例;单抗联合组接受信迪利单抗联合贝伐珠单抗治疗,纳入44例。记录两组患者治疗4个周期后的病情控制率和客观缓解率,比较治疗前、治疗2个周期后、治疗4个周期后血清VEGF和MMP-9水平变化,比较治疗毒副作用发生情况。随访6~30个月,绘制生存曲线,比较两组患者中位总生存时间(OS)和中位无进展生存时间(PFS)。结果 单抗联合组患者病情控制率和客观缓解率分别为77.27%和25.00%,对照组分别为44.44%和5.56%,差异有统计学意义(P<0.05)。治疗后,单抗联合组患者血清VEGF和MMP-9水平均随着时间降低,且低于对照组,差异有统计学意义(P<0.05)。单抗联合组患者甲状腺功能减退发生率为18.18%,对照组为2.78%,差异有统计学意义(P<0.05);单抗联合组患者脱发和手足综合征发生率均为0,对照组分别为22.22%和27.78%,差异均有统计学意义(P<0.05)。所有患者中位随访时间为18个月,单抗联合组患者中位OS和中位PFS分别为16.9个月和4.8个月,对照组患者中位OS和中位PFS分别为10.5个月和3个月,两组比较差异有统计学意义(P<0.05)。结论 信迪利单抗联合贝伐珠单抗治疗可以较好地控制不可切除肝细胞肝癌患者病情发展,显著降低血清肿瘤相关因子水平,提高生存率,且安全性较好。

肝细胞癌患者血清ECM1、MMP-9和VEGF水平的变化及其意义

目的 探究肝细胞癌患者血清细胞外基质蛋白-1(ECM1)、基质金属蛋白酶-9(MMP-9和血管内皮生长因子(VEGF)水平的变化及其意义。方法 对60例肝细胞癌患者进行回顾性分析,患者主要使用甲磺酸阿帕替尼进行治疗,必要时也可联合GEMOX方案肝动脉化疗栓塞术进行治疗。采用酶联免疫吸附法测定患者治疗前后的血清ECM1、VEGF、MMP-9水平。比较患者治疗前后ECM1、MMP-9和VEGF水平;比较不同临床病理特征(年龄、性别、血管侵犯、淋巴结转移、TNM分期、Edmondson分期和肿瘤直径)患者ECM1、MMP-9和VEGF水平。结果 治疗后,患者ECM1、MMP-9以及VEGF水平分别为(135.23±44.58)pg/ml、(421.25±87.56)μg/L和(657.56±54.56)pg/ml,均低于治疗前的(215.56±30.80)pg/ml、(499.56±30.56)μg/L、(798.02±50.79)pg/ml(P<0.05)。不同年龄、性别患者ECM1、MMP-9、VEGF水平比较差异无统计学意义(P>0.05);不同血管侵犯、淋巴结转移、TNM分期、Edmondson分期和肿瘤直径患者ECM1、MMP-9、VEGF水平比较差异具有统计学意义(P<0.05)。结论 ECM1、MMP-9、VEGF三者相互作用可促进肝癌细胞的转移,可根据其水平情况,了解患者肝细胞、肝功能健康状况。

3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术应用效果及对血清MMP-9和IGF-1水平的影响

目的:探究3D打印技术在经鼻蝶窦入路垂体腺瘤(PA)切除术的应用效果及对血清基质金属蛋白酶-9(MMP-9)和胰岛素样生长因子-1(IGF-1)水平的影响。方法:选取2020年5月至2022年5月秦皇岛市第一医院收治的84例PA患者,按照随机数表法将其分为观察组和对照组,每组42例。对照组行经鼻蝶窦入路垂体腺瘤切除术,观察组行经鼻蝶窦入路垂体腺瘤切除术联合应用3D打印技术,比较两组肿瘤切除效果、围术期指标、视力改善情况、MMP-9和IGF-1水平,以及鼻腔功能的鼻气道阻力(NAR)、T&T嗅觉测试评分及并发症。结果:观察组肿瘤切除效果优于对照组,差异有统计学意义(U=2.286,P<0.05);观察组手术时间、术中出血量及住院时间均少于对照组,差异有统计学意义(t=4.780、11.438、11.842,P<0.05);术后3 d、7 d时观察组血清MMP-9和IGF-1水平低于对照组,差异有统计学意义(F=7.526、4.985,P<0.05);术后1个月、3个月时观察组NAR及T&T嗅觉测试评分低于对照组,差异有统计学意义(F=6.359、8.436,P<0.05);两组视力视野改善情况及并发症发生率比较,差异无统计学意义(P>0.05)。结论:3D打印技术用于经鼻蝶窦入路垂体腺瘤切除术可提高肿瘤切除效果,优化手术操作,减少创伤,有利于减轻疼痛,改善嗅觉功能与视力视野,并能降低血清MMP-9、IGF-1水平,且安全性较高。

MMP-9与IGF-1在垂体腺瘤患者中的表达及其临床预测价值

目的探究MMP-9与IGF-1在垂体腺瘤患者中的表达及其临床预测价值。方法回顾性分析84例垂体腺瘤患者临床资料,分析不同病理垂体腺瘤患者的血清指标[基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)、胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)]水平差异。84例垂体腺瘤患者依据治疗后肿瘤直径大小和转移率分为缓解组(n=40)与未缓解组(n=44),采用受试者工作特征(ROC)曲线分析MMP-9、IGF-1对垂体腺瘤患者预后的评估效能。结果不同肿瘤直径的垂体腺瘤患者MMP-9、IGF-1水平比较无显著性差异(P>0.05);未发生淋巴结转移的患者MMP-9水平明显低于发生转移的患者,而IGF-1水平高于发生转移的患者,差异有统计学意义(P<0.05);临床分期为Ⅰ~Ⅱ期的垂体腺瘤患者MMP-9水平明显低于Ⅲ~Ⅳ期患者,而IGF-1水平高于Ⅲ~Ⅳ期患者,差异有统计学意义(P<0.05)。缓解组患者MMP-9低于同期未缓解组,IGF-1水平明显高于同期未缓解组患者,差异有统计学意义(P<0.05)。ROC曲线结果显示血清中MMP-9与IGF-1的截断值分别为16.61 ng/L、229.06 ng/L,MMP-9预测ROC曲线下面积(AUC)为0.871(95%CI=0.778~0.935),敏感度75.61%,特异度92.50%,IGF-1预测ROC曲线AUC为0.851(95%CI=0.755~0.921),敏感度75.61%,特异度87.50%。结论血清中MMP-9,IGF-1水平与垂体腺瘤患者临床病理特征及预后情况密切相关,可通过早期检测结果进一步优化诊治措施。

输卵管阻塞性不孕患者血清TGF-β1、IL-2、MMP-9水平及临床意义

目的:分析输卵管阻塞性不孕患者血清转化生长因子-β1(TGF-β1)、白细胞介素-2(IL-2)、基质金属蛋白酶-9(MMP-9)水平变化及临床意义。方法:以本院2022年3月-2023年10月诊治的60例输卵管阻塞性不孕患者为病例组,正常妊娠分娩的女性50例为对照组。测定对比两组血清TGF-β1、IL-2、MMP-9水平,Pearson相关性分析血清指标间相关性,受试者工作特征(ROC)曲线分析血清指标诊断不孕效能,logistic多因素回归分析输卵管阻塞性不孕发生影响因素。结果:病例组术前血清TGF-β1(593.79±148.23 ng/L)、IL-2(3.90±0.75 ng/L)、MMP-9(384.88±86.87 ng/ml)水平均高于对照组(239.42±113.37 ng/L、3.09±0.84 ng/L、178.98±80.85 ng/ml),术后血清TGF-β1、IL-2、MMP-9水平较术前均下降,血清TGF-β1与IL-2、MMP-9,及IL-2与MMP-9均呈正相关(均P<0.05)。ROC曲线分析,诊断不孕TGF-β1曲线下面积(AUC)0.941、敏感度88.3%、特异度94.0%,IL-2 AUC 0.778、敏感度66.7%、特异度84.0%,MMP-9 AUC 0.946、敏感度88.3%、特异度86.0%,3指标联合诊断AUC为0.992,敏感度93.3%、特异度100.0%。logistic回归分析,血清TGF-β1、IL-2、MMP-9异常升高是输卵管阻塞性不孕发发生的危险因素(均P<0.05)。结论:输卵管阻塞性不孕患者血清TGF-β1、IL-2、MMP-9水平均高表达,且是不孕发生的危险因素,3者联合检测对输卵管阻塞性不孕有较高诊断价值。

甲磺酸阿帕替尼联合多西他赛二线治疗晚期胃癌的效果及对外周血肿瘤异常蛋白、血管内皮生长因子与基质金属蛋白酶-9的影响

目的探讨甲磺酸阿帕替尼联合多西他赛二线治疗晚期胃癌的效果及对外周血肿瘤异常蛋白、血管内皮生长因子(VEGF)与基质金属蛋白酶-9(MMP-9)的影响。方法选取2020年3月至2022年3月收治的90例晚期胃癌患者为研究对象,随机将其分为对照组与观察组,各45例。对照组采用多西他赛化疗方案,观察组在对照组基础上加甲磺酸阿帕替尼治疗。比较两组的治疗效果。结果观察组的疾病控制率高于对照组(P<0.05)。治疗后,观察组的糖类抗原19-9(CA19-9)、肿瘤特异性生长因子(TSGF)及癌胚抗原(CEA)水平均低于对照组(P<0.05)。治疗后,观察组的VEGF、MMP-9、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平均低于对照组(P<0.05)。两组的不良反应总发生率比较,差异无统计学意义(P>0.05)。结论甲磺酸阿帕替尼联合多西他赛二线治疗晚期胃癌的效果较好,可对外周血肿瘤异常蛋白有良好的抑制作用,同时还能调节VEGF、MMP-9水平,且不会增加不良反应发生风险,值得应用与推广。

腹主动脉瘤患者血清转胶蛋白、基质金属蛋白酶9和核因子-κB p65水平检测及意义

目的:检测腹主动脉瘤(AAA)患者血清转胶蛋白(TAGLN)、基质金属蛋白酶9(MMP-9)和核因子-κB(NF-κB)p65水平变化,探讨其临床意义。方法:通过酶联免疫吸附法检测肾下AAA患者80例(AAA组)及体检健康者50例(健康组)血清TAGLN、MMP-9和NF-κB p65水平并进行比较。分析三者间的相关性,分析三者对AAA的诊断价值。结果:健康组血清TAGLN水平高于AAA组,MMP-9和NF-κB p65水平低于AAA组(均P<0.05)。血清TAGLN与MMP-9和NF-κB p65呈负相关(r=-0.196、-0.364,均P<0.05),MMP-9与NF-κB p65呈正相关(r=0.213,P=0.015)。TAGLN、MMP-9和NF-κB p65联合诊断AAA的曲线下面积(AUC)高于任意单独指标,而敏感度和特异度不低于任意单独指标(均P<0.05)。结论:AAA患者血清TAGLN水平升高,MMP-9和NF-κB p65水平降低,三者联合检测对AAA的诊断具有较高价值。

腹部创伤感染病人血清基质金属蛋白酶9、基质细胞衍生因子1表达及其诊断价值

目的 探究腹部创伤感染病人血清基质金属蛋白酶(MMP)-9、基质细胞衍生因子(SDF)-1表达及其诊断价值。方法 2021年7月~2022年7月收治的腹部创伤感染病人100例,作为病例组,同期腹部创伤未发生感染的病人100例为对照组。采用酶联免疫吸附法(ELISA)检测血清MMP-9、SDF-1水平;Spearman法分析血清MMP-9、SDF-1与SIRS评分和住院时间的相关性。ROC曲线分析血清MMP-9、SDF-1对腹部创伤感染病人的诊断价值。配对样本t检验分析腹部创伤感染病人治疗前后血清MMP-9、SDF-1水平。多因素Logistic回归分析影响腹部创伤感染发生的因素。结果 病例组病人血清MMP-9、SDF-1水平、C-反应蛋白(CRP)、白细胞计数(WBC)、血清中肿瘤坏死因子(TNF)-α、合并糖尿病、创伤类型等与对照组比较,差异有统计学意义(P<0.05)。腹部创伤感染病人血清MMP-9水平分别与SIRS评分、CRP、WBC、TNF-α呈正相关性(r=0.505、0.471、0.423、0.416,P<0.05);血清SDF-1水平分别与SIRS评分、CRP、WBC、TNF-α也呈正相关性(r=0.469、0.439、0.518、0.469,P<0.05)。ROC分析显示,血清MMP-9、SDF-1预测腹部创伤发生感染的曲线下面积(AUC)分别为0.850(95%CI:0.799~0.902)、0.806(95%CI:0.746~0.866),二者联合检测的AUC为0.914(95%CI:0.876~0.951),高于MMP-9、SDF-1单独检测(Z=1.987、2.97,P<0.05)。治疗后血清MMP-9、SDF-1表达水平低于治疗前,差异有统计学意义(P<0.05)。Logistic回归分析显示,合并糖尿病、创伤类型、血清MMP-9、SDF-1水平是腹部创伤病人感染的危险因素(P<0.05)。结论 腹部创伤感染病人血清MMP-9、SDF-1水平升高,二者可能参与腹部创伤感染的发生发展,对腹部创伤感染的诊断具有临床意义。

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.

Contrary Regulation of TIMP-1 and MMP-9 by Hepatocyte Growth Factor Antibody after Lung Injury

Objective To study the influence of hepatocyte growth factor (HGF) antibody on the lung expression level of matrix metalloproteinases-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Methods Thirty male Wistar rats were randomly divided into 3 groups: control group, model group, and intervention group. Endotoxin was intratracheally infused in the model and intervention groups. HGF antibody was injected in the rats of the intervention group from day 1 to day 14, while the same volume of saline was injected in the control group. The rats were sacrificed on day 28 after endotoxin treatment. The amounts of MMP-9 mRNA and TIMP-1 mRNA were measured by reverse transcription-polymerase chain reaction, and protein expression levels of MMP-9 and TIMP-1 were measured by immunohistochemistry. Results In the model group, both mRNA and protein expression levels of TIMP-1 were significantly increased, the same as MMP-9. In the intervention group, the increase of TIMP-1 was remarkably reduced compared with the model group, while the mRNA and protein expression levels of MMP-9 were still increased. Conclusion HGF activity may accelerate the repair of lung injury through contrary regulating the expression levels of TIMP-1 and MMP-9.

Matrix metalloproteinases contribute to kidney fibrosis in chronic kidney diseases

Matrix metalloproteinases(MMPs) are members of the neutral proteinase family. They were previously thought to be anti-fibrotic because of their ability to degrade and remodel of extracellular matrix. However, recent studies have shown that MMPs are implicated in initiation and progression of kidney fibrosis through tubular cell epithelial–mesenchymal transition(EMT) as well as activation of resident fibroblasts, endothelial-mesenchymal transition(Endo MT) and pericyte-myofibroblast transdifferentiation. Interstitial macrophage infiltration has also been shown to correlate with the severity of kidney fibrosis in various chronic kidney diseases. MMPs secreted by macrophages, especially MMP-9, hasbeen shown by us to be profibrotic by induction of tubular cells EMT. EMT is mainly induced by transforming growth factor-β(TGF-β). However, MMP-9 was found by us and others to be up-regulated by TGF-β1 in kidney tubular epithelial cells and secreted by activated macrophages, resulting in EMT and ultimately kidney fibrosis. Therefore, MMP-9 may serve as a potential therapeutic target to prevent kidney fibrosis in chronic kidney disease. This review, by a particular focus on EMT, seeks to provide a comprehensive understanding of MMPs, especially MMP-9, in kidney fibrosis.