The relationship between matrix metalloproteinases-9 and CD15s antigen in angiogenesis of gastric carcinoma

Objective： To investigate the relationship between matrix metalloproteinases-9 （MMP-9） and sialyl Lewis X （CD15s） antigen in invasion and metastasis of gastric carcinoma. Methods： Expression of CD105, MMP-9 and CD15s in 47 cases of gastric carcinoma undergone radical surgery were evaluated by SP immunohistochemical staining using the respective monoclonal antibody. The microvessel density （MVD） marked with CD105 was detected. Correlation between MVD and MMP-9, CD15s was also statistically analyzed. Results： The MVD in both MMP-9 and CD15s positive expression group was higher significantly than that in MMP-9 or CD15s positive expression alone group, and it was also significantly higher than that in both MMP-9 and CD15s negative expression group. Conclusion： MMP-9 is a marker of invasion and CD15s is a marker of metastasis in gastric carcinoma. Combining detection of MMP-9 and CD15s has certain clinical significance for diagnosis, treatment and assessing the prognosis for gastric caner.

Effects of Kaiqiao Huazhuo prescription on the content of Matrix metallopro teinases-9 in brain of focal cerebral ischemia rats

OBJECTIVE:To observe the effect of Kaiqiao Huazhuo prescription on the content of Matrix metallopro teinases-9(MMP-9)in brain of focal cerebral ischemia rats.METHODS:The model of focal cerebral ischemia was established by inserting nylon thread,the effect of Kaiqiao Huazhuo prescription on brain edema and the content of MMP-9 in brain of focal cerebral ischemia rats were observed 6 h,12 h,24 h and 48 h after cerebral ischemia respectively and was compared with effect of Buchangnaoxintong.RESULTS:6 h after cerebral ischemia,compared with sham operation group,the content of MMP-9 in brain increased,and it reached peak value in 24 h(P<0.01);the change of brain edema is similar to that of MMP-9.Compared with model group,the content of MMP-9 in brain and the brain edema of each treatment groups were decreased(P<0.05 or P<0.01).CONCLUSIONS:Through decreasing the content of MMP-9 in brain of focal cerebral ischemia rats,Kaiqiao Huazhuo prescription could protect blood brain barrier and reduce brain edema.

Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice

AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.

Expressions of cyclooxygenase-2 and matrix metalloproteinase-9 in cervical carcinoma and their clinical significance

Objective: To investigate the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 in cervical carcinoma and their clinical significance. Methods: Immunohistochemistry SP method was used to detect the expres- sions of COX-2 and MMP-9 in 72 cases of invasive carcinoma of cervix (ICC) and 16 cases of normal cervical epithelium remote from tumor (NCE). The relationships between the expressions of COX-2, MMP-9 in ICC and some characteristics relating to clinical pathology of cervical carcinoma such as histological grading, lymph node metastasis, stromal invasion and FIGO stage were analyzed statistically. Results: The rates of the positive expressions of COX-2 and MMP-9 in ICC were significantly higher than those in NCE. COX-2: 88.9% (64/72) in group ICC and 12.5% (2/16) in group NCE, P = 0.000; MMP-9: 94.4% (68/72) in group ICC and 43.8% (7/16) in group NCE, P = 0.000. The expression of COX-2 was positively correlated with lymph node metastasis (r = 0.296, P = 0.012) and stromal invasion (r = 0.257, P = 0.029). The expression of MMP-9 was positively correlated with FIGO stage (r = 0.329, P = 0.005) and histological grading (r = 0.351, P = 0.003). The expression of COX-2 was positively correlated with the expression of MMP-9 in ICC (r = 0.297, P = 0.011). Conclusion: The overexpressions of COX-2 and MMP-9 were closely related to the invasion and growth of cervical carcinoma. The tissue with the overexpression of COX-2 had strong invasion ability. COX-2 and MMP-9 had synergistic effect on proliferation, invasion and metastasis of cancer cells. Detecting the coexpression of COX-2 and MMP-9 may be of value in further understanding the biological behavior and predicting the prognosis of cervical carcinoma.

Association of Matrix Metalloproteinase-9 and p53 Gene Polymorphisms with Genetic Susceptibility to No-small-cell Lung Cancer

Matrix metalloproteinase-9（MMP-9） and p53 genes play an essential role in the multi-step process of tumorigenesis in lung cancer. Single nucleotide polymorphisms（SNPs） of MMP-9 and p53 genes are associated with the risk and progression of many cancers. In this study, we evaluated the association of the R279Q polymorphism of MMP-9 or the A1/A2 polymorphism of p53 gcne with the risk of no-small-cell lung cancer（NSCLC） in Han population of Northeast China. We examined the frequency of SNPs in the two kinds of genes of 50 patients with NSCLC and 50 cancer-free controls frequency-matched by age and sex. Polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） technique was used to determine the genotypes. The results indicate that the 279RR genotype in MMP-9 gene and the A1/A2 genotype in p53 gene show a significantly increased risk of NSCLC. Therefore, the MMP-9 279RR and p53 A1/A2 genotypes may be used as markers for susceptibility to NSCLC in Han population of Northeast China.

Matrix Metalloproteinase-9 in the Etiopathogenesis of Placenta Accreta Spectrum:A Literature Review

The recent increase in placenta accreta spectrum has been correlated with a rise in the rate of cesarean sections.A recent study provides evidence that hampered wound healing results in cesarean scar defects that lead to a failure in the normal process of decidualization and deeper adherence of trophoblasts.Matrix metalloproteinase(MMP)is crucial in every step of wound healing as it alters the wound matrix,facilitating cell migration,as well as tissue remodeling.MMP-9 expression is higher in placental and decidual tissue in cases of placenta accreta.Based on these findings,assessment of MMP-9 expression can shed new light on the etiopathology of placenta accreta spectrum disorder and can be a potential diagnostic marker.

氯沙坦对脑缺血再灌注损伤大鼠血脑屏障通透性和MMP-9表达的影响

目的观察血管紧张素Ⅱ受体阻断药氯沙坦对大鼠局灶性脑缺血再灌注损伤后血脑屏障通透性和基质金属蛋白酶-9(MMP-9)表达的影响。方法采用血管内栓线阻断法制备大鼠局灶性脑缺血再灌注损伤模型,于脑缺血2 h、再灌注24 h后测定脑组织含水量、伊文斯蓝(EB)含量,免疫组织化学方法测定MMP-9表达。结果脑缺血2 h、再灌注24 h,大鼠脑组织含水量及EB含量增加,MMP-9呈现高表达。而氯沙坦组脑组织含水量、EB含量及MMP-9表达明显低于脑缺血再灌注组(P<0.05)。结论氯沙坦通过降低脑缺血再灌注大鼠基质金属蛋白酶-9的活性及血脑屏障通透性,从而发挥其脑缺血再灌注损伤的保护作用。

鼻息肉中MMP-9和NF-κB的表达研究

目的 研究鼻息肉MMP 9和NF κB的表达及其意义。方法 应用免疫组化的方法检测正常鼻黏膜和鼻息肉MMP 9和NF κB的表达 ,图像分析系统进行半定量。结果 MMP 9在正常对照组中有弱阳性表达 ,而鼻息肉组的表达显著增强 ,主要在上皮细胞、炎症细胞、内皮细胞和腺上皮细胞中表达。NF κB在正常对照组的胞浆呈弱阳性表达 ,而在鼻息肉的上皮细胞、炎症细胞和间质细胞的细胞核内表达呈强阳性 ;两种因子表达显著相关。结论 NF κB和MMP 9的表达可能对鼻息肉的发生和发展有重要作用 ,而且在鼻息肉中NF κB可能对MMP 9的表达也有调控作用。

不同抗氧化剂对胎膜组织MMP-9表达的影响

目的:检测不同抗氧化剂α-硫辛酸(α-LA)和维生素C(Vit C)+维生素E(Vit E)对体外培养的胎膜早破(PROM)胎膜组织基质金属蛋白酶9(MMP-9)表达的影响。方法:选取发生胎膜早破的孕妇8例,未临产,剖宫产终止妊娠,其中未足月胎膜早破组(PPROM)和足月胎膜早破组(TPROM)各4例。每例胎膜组织分成3组,分别加入磷酸盐缓冲液(PBS,即对照组)、0.5 mmol/Lα-LA和28.8 g/L Vit C+1.8 g/L Vit E后进行体外培养24h,采用免疫组化染色方法和Western blotting技术检测胎膜组织中MMP-9蛋白表达。结果:(1)免疫组化结果显示:TPROM组织中MMP-9定位于绒毛膜细胞和中性粒细胞的胞浆,且3组间MMP-9平均积分吸光度值无显著差异(P>0.05),而PPROM组织中MMP-9除在绒毛膜细胞和中性粒细胞的胞浆中表达外,在羊膜上皮细胞的胞浆中也强阳性表达,α-LA组及Vit C+Vit E组MMP-9积分吸光度值(0.0212±0.0057和0.0107±0.0009)低于对照组(0.0618±0.0098),Vit C+Vit E组较α-LA组更低(P<0.01)。(2)Western blotting结果显示,TPROM组织中,3组中pro-MMP-9表达水平均无显著差异(P>0.05),但α-LA组及Vit C+Vit E组active MMP-9蛋白相对表达水平(0.64±0.07和0.28±0.13)低于对照组(0.99±0.22),Vit C+Vit E组较α-LA组更低(P<0.05)。在PPROM组织中,α-LA组和Vit C+Vit E组pro-MMP-9/active MMP-9蛋白相对表达水平(0.69±0.08/0.35±0.07和0.38±0.03/0.16±0.05)低于对照组(1.00±0.20/1.00±0.10),Vit C+Vit E组较α-LA组更低(P<0.05)。结论:抗氧化剂可使胎膜早破胎膜组织的MMP-9表达水平下调,且28.8 g/L Vit C+1.8 g/L Vit E作用后的MMP-9表达水平较0.5 mmol/Lα-LA下调更明显,这为胎膜早破胎膜组织的防治提供理论依据。

TSP-1和MMP-9在乳腺癌组织中的表达意义

目的探讨乳腺癌组织中凝血酶敏感蛋白1(TSP-1)和基质金属蛋白酶9(MMP-9)的表达及其与肿瘤微血管生成、患者预后的关系。方法采用免疫组织化学方法检测131例乳腺癌患者组织中TSP-1、MMP-9的表达情况,比较研究指标的表达情况和肿瘤组织中微血管密度(MVD)及其与患者临床病理特征、预后的关系。结果 131例中,肿瘤间质中TSP-1的表达和肿瘤的MVD呈负相关(Spearman相关系数=-0.241,P=0.006);肿瘤细胞中MMP-9与肿瘤间质中TSP-1共同高表达与乳腺癌组织大小、淋巴结转移、病理分期密切相关(P<0.05);生存分析发现二者共同高表达的患者相对于二者非共同高表达的患者预后不佳。结论乳腺癌组织中MMP-9联合TSP-1共同高表达可作为评价乳腺癌预后有价值的标记物。

丹参多酚酸盐对肺癌模型小鼠肺组织中VEGF和MMP-9表达的影响

目的:研究丹参多酚酸盐对肺癌模型小鼠肺组织中血管内皮生长因子(VEGF)和基质金属蛋白酶9(MMP-9)表达的影响。方法:取C57BL/6小鼠随机分为模型组(生理盐水)、阳性对照组(环磷酰胺50 mg/kg)和丹参多酚酸盐低、中、高剂量组(20、40、80 g/kg),每组10只。小鼠ip乌拉坦1 000 mg/kg,每周2次,连续4周建立肺癌模型;建模后各组小鼠ip相应药物,每日1次,连续给药14 d。比较各组小鼠行为、体征、体质量、抑瘤率、脾脏系数、胸腺系数及肺组织中血管内皮生长因子(VEGF)和基质金属蛋白酶9(MMP-9)表达。结果:模型组小鼠活动度消失,毛色暗淡无光泽,喜扎堆;阳性对照组和丹参多酚酸盐各剂量组小鼠上述现象均好转。阳性对照组和丹参多酚酸盐低、中、高剂量组小鼠的体质量分别为(21.01±2.95)g、(20.89±3.14)g、(21.03±3.02)g、(21.24±3.17)g,抑瘤率分别为(41.12±15.42)%、(36.92±10.42)%、(39.41±12.39)%、(37.19±10.39)%;与模型组比较,其余4组小鼠的脾脏系数、胸腺系数、VEGF(阳性对照组除外)和MMP-9表达均明显降低(P<0.05)。结论:丹参多酚酸盐对肺癌模型小鼠有明显的抑瘤作用,其作用机制可能与抑制VEGF和MMP-9表达相关。

乌司他汀联合甲基泼尼松龙治疗百草枯中毒的临床疗效及对MMP-9的影响

目的评价乌司他汀联合甲基泼尼松龙治疗百草枯中毒的临床疗效及对MMP-9的影响。方法对48例百草枯中毒患者分成常规治疗组和联合治疗组,联合治疗组在常规治疗基础上联用乌司他汀及甲基泼尼松龙,检测两组的MMP-9水平,并比较两组ALI/ARDS、MODS、死亡例数及死亡存活天数。结果联合治疗组的ALI/ARDS、MODS、死亡例数及死亡存活天数显著优于常规治疗组,MMP-9显著降低(P<0.05)。结论早期联合应用乌司他汀及甲基泼尼松龙治疗百草枯中毒能显著降低MMP-9水平,减缓肺间质纤维化的形成,提高百草枯中毒救治的成功率。

苦参碱抑制人肝癌HepG2细胞增殖及其对VEGF、MMP-9表达的影响

目的研究苦参碱(matrine,Ma)抑制人肝癌HepG2细胞增殖及其对血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶-9(matrix meta-lloproteinase-9,MMP-9)表达的影响,探讨其抗肝癌作用可能的分子机制。方法设Ma组和阴性对照组,Ma组设5个药物梯度,采用0.2 mg/ml、0.4 mg/ml、0.8 mg/ml、1.6mg/ml、3.2mg/ml浓度的苦参碱分别作用于对数生长期的HepG2细胞,MTT法检测苦参碱对细胞生长的抑制作用,Real-time PCR检测VEGF mRNA表达,蛋白质印迹法(Western Blot,WB)检测VEGF和MMP-9蛋白的表达。结果苦参碱能抑制人肝癌HepG2细胞增殖,呈时间和剂量依赖性。苦参碱能下调VEGF mRNA表达(P<0.05)和VEGF、MMP-9蛋白的表达(P<0.05)。结论苦参碱在体外能抑制肝癌细胞增殖,呈时间和剂量依赖性,其可能的分子机制是通过下调VEGF和MMP-9蛋白表达,抑制肝癌血管生成,进而起到抗肝癌作用。

MMP-2、MMP-9在膀胱移行细胞癌组织中的表达及其临床意义

目的观察膀胱移行细胞癌组织中基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)的表达情况,并探讨其表达的临床意义。方法选取海南省农垦三亚医院2012年1月至2015年1月收治的30例膀胱移行细胞癌组织标本作为观察组,另选取非膀胱肿瘤手术中切术的正常膀胱组织标本30例作为对照组,对所有标本黏膜中MMP-2、MMP-9的表达情况与表达强度通过免疫组化SP法联合高清晰度彩色医学图文分析系统进行检测,分析其表达的临床意义。结果观察组标本中的MMP-2、MMP-9的表达比对照组标本的表达明显增高,差异均有统计学意义(P<0.05),且MMP-2、MMP-9在正常膀胱上皮呈阴性表达;观察组标本中的MMP-2、MMP-9呈现高表达状态,且表达强度随着疾病分期、分级的增高而逐渐增高,差异均有统计学意义(P<0.05)。结论在膀胱癌侵袭转移过程中,存在MMP-2、MMP-9的参与,在膀胱移行细胞癌中MMP-2、MMP-9的表达对其预后判断具有非常重要的参考价值。

脑泰方提取物干预大鼠脑缺血后MMP-9-mRNA及PA-mRNA表达研究

目的研究大鼠脑缺血后益气活血中药脑泰方提取物(黄芪、川芎、地龙、僵蚕)干预对缺血区脑水肿及MMP-9-mRNA、PA-mRNA表达的影响。方法随机将SD大鼠分为假手术组、模型组、脑泰方提取物(NTE)低、中、高剂量组(3,9,27g/kg)。各组大鼠预处理ig给药连续3d,每日1次,MCAO模型制备术后ig给药1d。术后1d取材检测各组脑组织含水量,RT-PCR检测MMP-9-mRNA及PA-mRNA表达。结果实验表明高、中NTE组与模型组比较,脑含水量均有明显降低(P<0.05)。NTE高剂量组脑缺血区MMP-9-mRNA、PA-mRNA表达明显降低(P<0.05)。结论脑泰方提取物干预可减轻脑水肿的发生,可能是通过降低MMP-9-mRNA及PA-mRNA的表达,减少MMP-9、PA的生成,发挥保护急性脑缺血血脑屏障的作用。

氟伐他汀对早期糖尿病肾病患者Hcy、APN、MMP-9和mAlb的影响

目的观察氟伐他汀对早期糖尿病肾病(DN)患者尿微量白蛋白(m Alb)、同型半胱氨酸(Hcy)、脂联素(APN)、基质金属蛋白酶-9(MMP-9)的影响。方法 58例早期糖尿病肾病患者随机分为氟伐他汀组30例和饮食治疗组28例,两组患者疗程均为8周,同时选取55例血糖正常人群作为对照组,分别检测对照组和早期DN组患者治疗前后的m Alb、Hcy、APN、MMP-9、ALT水平,并对检测结果进行统计学分析。结果氟伐他汀组、饮食治疗组治疗前的m Alb、Hcy、MMP-9水平均显著高于对照组,APN水平显著低于对照组,差异均有显著统计学意义(P<0.01),而ALT水平比较则差异无统计学意义(P>0.05);饮食治疗组治疗后m Alb水平与治疗前比较显著下降(P<0.01),而Hcy、APN、MMP-9水平变化不明显(P>0.05);氟伐他汀组治疗后Hcy、MMP-9、m Alb水平与治疗前比较均显著下降,APN水平显著升高,差异均有显著统计学意义(P<0.01)。结论 Hcy、APN、MMP-9水平与糖尿病肾病密切相关,氟伐他汀有降低Hcy、MMP-9、m Alb及升高APN的作用。

慢性肾衰竭患者血清MMP-9和TIMP-1表达及意义

目的检测慢性肾衰竭（CRF）患者血清基质金属蛋白酶-9（MMP-9）及金属蛋白酶组织抑制因子-1（TIMP-1）表达状况，拟在探讨其与肾脏纤维化的关系。方法采用ELISA法测定60例CRF患者（氮质血症期15例，肾衰竭期24例，尿毒症终末期21例）和20例正常对照组血清MMP-9、TIMP-1水平，同时收集患者临床资料，分析血清MMP-9、TIMP-1水平和MMP-9／TIMP-1比值与肾功能损害等临床指标之间的相关性。结果CRF患者各期血清MMP-9、TIMP-1水平明显升高，MMP-9／TIMP-1比值显著降低，随着肾小球滤过率（GFR）下降，MMP-9、TIMP-1呈降低趋势，而MMP-9／TIMP-1比值却逐渐上升。血清TIMP-1水平和MMP-9／TIMP-1比值与血肌酐、GFR及血红蛋白呈高度相关性。结论血清MMP-9、TIMP-1参与了CRF的进展，血清TIMP-1水平或MMP-9／TIMP-1比值能较好地反映肾脏纤维化的程度。

慢性阻塞性肺疾病患者血清基质金属蛋白酶-9和金属蛋白酶抑制剂-1的表达及其对肺血管重塑的预测价值

目的探讨基质金属蛋白酶-9(matrix metalloproteinase,MMP-9)、基质金属蛋白酶抑制剂-1(matrix metalloproteinase inhibitor,TIMP-1)在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者血清中表达的相关性及其对肺血管重塑(pulmonary vascular remodeling,PVR)的预测价值。方法选取2019年1月至2021年12月住院治疗的COPD患者1091例作为研究对象,根据临床诊断将患者分为急性加重期组和稳定期组,对COPD患者血清MMP-9、TIMP-1表达水平进行比较,对统计结果进行相关性分析。并对患者血清MMP-9、TIMP-1表达与肺血管重塑预测的特异性进行比较。结果急性加重期COPD患者血清MMP-9、TIMP-1相对表达量均显著高于稳定期组患者(P<0.01)。经Pearson相关性分析,MMP-9、TIMP-1在COPD患者血清中表达呈显著正相关。肺血管重塑发生患者血清MMP-9、TIMP-1水平急性加重期表达水平高于与稳定期。MMP-9、TIMP-1预测肺血管重塑的效能分析,COPD患者急性加重期特异性与稳定期特异性比较,差异有统计学意义(P<0.01)。结论COPD患者血清MMP-9、TIMP-1的表达,可作为COPD病情评估和PVR预测的血清学生物参考标志物,具有重要的临床意义。

阿托伐他汀对大鼠颈动脉粥样硬化易损斑块及hs-CRP和MMP-9表达的影响

目的研究阿托伐他汀对大鼠颈内动脉粥样硬化易损斑块面积、数目及对基质金属蛋白酶9(MMP-9)表达和血清hs-CRP的影响。方法将48只健康雄性SD大鼠随机分为对照组、模型组、常规剂量组、强化剂量组,14 w后采血测量hs-CRP,光镜下观察颈内动脉粥硬化易损斑块病理学变化,计数易损斑块数目及面积,采用免疫组织化学法检测易损斑块中MMP-9的表达。结果与模型组相比,常规剂量组和强化剂量组易损斑块计数、面积大小、MMP-9表达均明显降低(P<0.01),强化剂量组又低于常规剂量组(P<0.05),强化剂量组和常规剂量组血清hs-CRP测定结果均明显低于模型组(P<0.01),强化剂量组又低于常规剂量组(P<0.05)。结论阿托伐他汀能够稳定及减少颈内动脉粥样硬化易损斑块的形成和进展,对血清hs-CRP及MMP-9的表达具有抑制作用,并且其抑制作用与剂量具有量效关系。