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对急性呼吸窘迫综合征并脓毒性休克患者的早期诊断及预后评估价值研究

目的探讨基质金属蛋白酶-9(MMP-9)对急性呼吸窘迫综合征(ARDS)并脓毒性休克患者早期诊断和预后评估的价值。方法选取2020年4月至2023年4月广西壮族自治区人民医院收治的113例ARDS患者为研究对象,根据患者确诊后24 h内休克发生情况将其分为ARDS并脓毒性休克组(61例)和ARDS非脓毒性休克组(52例)。选取同期22名健康志愿者作为正常对照组。根据患者治疗后28 d转归情况,将ARDS并脓毒性休克组患者分为存活组(27例)和死亡组(34例)。比较各组一般资料以及MMP-9表达水平。采用受试者工作特征(ROC)曲线评估MMP-9对ARDS并脓毒性休克患者早期诊断的准确性。采用logistic回归分析探讨ARDS并脓毒性休克患者预后的影响因素。结果ARDS并脓毒性休克组、ARDS非脓毒性休克组的MMP-9表达水平均高于正常对照组,ARDS非脓毒性休克组的MMP-9表达水平高于ARDS并脓毒性休克组,差异有统计学意义(P<0.05)。ROC曲线分析结果显示,MMP-9可有效预测ARDS并脓毒性休克的发生[AUC(95%CI)=0.666(0.565~0.767)],其最佳临界值为28.53 ng/mL,对应的灵敏度为47.50%,特异度为94.20%。多因素logistic回归分析结果显示,MMP-9[OR(95%CI)=0.976(0.954~0.999)]、氧合指数[OR(95%CI)=0.978(0.957~1.000)]、IL-6[OR(95%CI)=1.004(1.000~1.008)]是ARDS并脓毒性休克患者死亡的影响因素(P<0.05)。ROC曲线分析结果显示,MMP-9可有效预测ARDS并脓毒性休克患者的预后[AUC(95%CI)=0.735(0.605~0.865)],其最佳临界值为33.83 ng/mL,对应的灵敏度为70.59%,特异度为77.78%。结论MMP-9对ARDS并脓毒性休克有较好的早期诊断价值,对ARDS并脓毒性休克患者的病情严重程度及预后有一定的预测作用。

天麻健脑颗粒联合高压氧对血管性痴呆患者炎症因子、MMP-9、Hcy和SOD表达的影响研究

【目的】探讨天麻健脑颗粒(由半夏白术天麻汤衍化)与高压氧联合治疗对血管性痴呆(vascular dementia,VD)患者认知功能、日常生活能力及血清炎症因子、基质金属蛋白酶9(MMP-9)、同型半胱氨酸(Hcy)和超氧化物歧化酶(SOD)表达的影响。【方法】将100例风痰瘀阻型VD患者随机分为试验组和对照组,每组各50例。2组患者均给予控制血压、降糖、调脂等对症治疗,对照组同时给予奥拉西坦胶囊口服治疗,观察组在对照组的基础上给予天麻健脑颗粒联合高压氧治疗,疗程为12周。观察2组患者治疗前后中医证候积分、简易精神状态量表(MMSE)评分、日常生活能力评定量表(ADL)评分和血清炎症因子、神经因子、凋亡因子及MMP-9、Hcy、SOD表达水平的变化情况。【结果】(1)量表评分方面,治疗后,2组患者的中医证候积分和ADL评分均较治疗前明显降低(P<0.05),MMSE评分均较治疗前明显升高(P<0.05),且试验组对中医证候积分和ADL评分的降低幅度及对MMSE评分的升高幅度均明显优于对照组(P<0.01)。(2)炎症因子方面,治疗后,2组患者的血清肿瘤坏死因子α(TNF-α)、C反应蛋白(CRP)、白细胞介素6(IL-6)水平均较治疗前明显降低(P<0.05),且试验组对血清TNF-α、CRP、IL-6水平的降低幅度均明显优于对照组(P<0.01)。(3)神经因子方面,治疗后,2组患者的血清去甲肾上腺素(NE)、多巴胺(DA)、5-羟色胺(5-HT)水平均较治疗前明显升高(P<0.05),且试验组对血清NE、DA、5-HT水平的升高幅度均明显优于对照组(P<0.01)。(4)凋亡因子方面,治疗后,2组患者的血清血红素加氧酶1(HO-1)水平均较治疗前明显升高(P<0.05),血清可溶性凋亡相关因子(sFAS)及其配体(sFASL)水平均较治疗前明显降低(P<0.05),且试验组对血清HO-1水平的升高幅度及对血清sFAS、sFASL水平的降低幅度均明显优于对照组(P<0.01)。(5)MMP-9、Hcy、SOD表达水平方面,治疗后,2组患者的血清SOD水平均较治疗前明显升高(P<0.05),血清MMP-9、Hcy水平均较治疗前明显降低(P<0.05),且试验组对血清SOD水平的升高幅度及对血清MMP-9、Hcy水平的降低幅度均明显优于对照组(P<0.01)。【结论】天麻健脑颗粒联合高压氧能够改善VD患者的认知功能与生活能力,并具有良好的抗炎、抗氧化、调节神经递质表达的作用。

通窍化栓汤联合长春西汀及阿司匹林治疗急性脑梗死的疗效及对血液流变学和血清S100B、MMP-9的影响

【目的】探讨通窍化栓汤(由大血藤、见血飞和血三七等中药组成)联合长春西汀及阿司匹林治疗急性脑梗死的疗效及对血液流变学、血清钙结合蛋白(S100B)和基质金属蛋白酶9(MMP-9)水平的影响。【方法】将116例急性脑梗死气虚血瘀证患者随机分为对照组和观察组,每组各58例。2组患者入院后均给予对症及维持生命体征平稳、控制血压、降颅内压等常规治疗。在此基础上,对照组患者给予阿司匹林肠溶片联合长春西汀治疗,观察组在对照组的基础上给予通窍化栓汤治疗,疗程为14 d。观察2组患者治疗前后中医证候积分、美国国立卫生研究院卒中量表(NIHSS)评分、日常生活活动能力(ADL)评分、血液流变学指标、血小板功能指标和血清S100B、MMP-9水平的变化情况,并评价2组患者的临床疗效。【结果】(1)临床疗效方面,治疗14 d后,观察组的总有效率为91.38%(53/58),对照组为77.59%(45/58),组间比较(χ2检验),观察组的疗效明显优于对照组(P<0.05)。(2)量表评分方面,治疗后,2组患者的中医证候积分、NIHSS评分均较治疗前明显降低(P<0.05或P<0.01),ADL评分均较治疗前明显升高(P<0.05),且观察组对中医证候积分、NIHSS评分的降低幅度和对ADL评分的升高幅度均明显优于对照组(P<0.01)。(3)血液流变学指标方面,治疗后,2组患者的全血高切黏度、全血低切黏度、血浆黏度和纤维蛋白原水平均较治疗前明显降低(P<0.05),且观察组的降低幅度均明显优于对照组(P<0.05或P<0.01)。(4)血小板功能指标方面,治疗后,2组患者的血小板聚集率(PAgT)、血小板黏附率(PAdT)水平均较治疗前明显降低(P<0.05),且观察组的降低幅度均明显优于对照组(P<0.01)。(5)血清S100B和MMP-9水平方面,治疗后,2组患者的血清S100B和MMP-9水平均较治疗前明显降低(P<0.05),且观察组的降低幅度均明显优于对照组(P<0.01)。【结论】通窍化栓汤联合长春西汀和阿司匹林治疗急性脑梗死效果显著,可有效改善患者血液流变学指标和血小板功能,降低血清S100B和MMP-9表达水平,提高患者日常生活能力。

生殖道感染对足月和未足月胎膜早破孕妇宫颈分泌液MMP-2、MMP-9表达及不良母婴结局的影响

目的分析生殖道感染对足月和未足月胎膜早破(PROM)孕妇基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)表达及不良母婴结局的影响。方法招募2021年6月至2023年6月就诊于湖北医药学院附属十堰市太和医院的110例PROM孕妇作为研究对象。根据生殖道感染情况和孕周将其分为未足月胎膜早破(pPROM)感染组(34例)、pPROM非感染组(26例)、足月胎膜早破(tPROM)感染组(34例)、tPROM非感染组(16例)。比较四组一般资料、宫颈分泌液MMP-2和MMP-9表达水平以及不良母婴结局发生情况,采用多因素logistic回归分析PROM孕妇发生不良母婴结局的影响因素。结果四组年龄、孕次、体质量指数、吸烟史、饮酒史比较差异无统计学意义(P>0.05)。四组宫颈分泌液MMP-2、MMP-9表达水平比较差异有统计学意义(P<0.05),其中pPROM感染组宫颈分泌液MMP-2、MMP-9表达水平高于pPROM非感染组和tPROM非感染组,tPROM感染组宫颈分泌液MMP-2、MMP-9表达水平高于tPROM非感染组,差异有统计学意义(P<0.05)。四组绒毛膜羊膜炎及不良母婴结局总发生率比较差异有统计学意义(P<0.05),其中pPROM感染组绒毛膜羊膜炎发生率高于tPROM感染组和tPROM非感染组,不良母婴结局总发生率高于pPROM非感染组和tPROM非感染组,差异有统计学意义(P<0.05)。多因素logistic回归分析结果显示,生殖道感染及较高的宫颈分泌液MMP-2、MMP-9表达水平是PROM孕妇发生不良母婴结局的独立危险因素(P<0.05)。结论生殖道感染可增加足月和未足月PROM孕妇宫颈分泌液MMP-2、MMP-9表达水平,生殖道感染及较高的宫颈分泌液MMP-2、MMP-9表达水平是PROM孕妇发生不良母婴结局的独立危险因素。

CT灌注成像参数与血清CTRP-3、LDL-C及MMP-9对急性脑梗死后出血转化的评价

目的:探讨CT灌注成像参数与血清补体C1q/肿瘤坏死因子相关蛋白-3(CTRP-3)、低密度脂蛋白胆固醇(LDL-C)及基质金属蛋白酶-9(MMP-9)对急性脑梗死(ACI)后出血转化(HT)的评价。方法:选取2019年8月至2022年7月于简阳市人民医院诊治的206例ACI患者,根据患者静脉溶栓后是否发生HT分为HT组(45例)和非HT组(161例),对比两组CT灌注成像参数[血流量(BF)、血容量(BV)、平均通过时间(MTT)、表面通透性(PS)]、CTRP-3、LDL-C及MMP-9;采用受试者工作特征曲线(ROC)模型分析CT灌注成像参数、CTRP-3、LDL-C及MMP-9诊断HT的曲线下面积(AUC)值、灵敏度及特异度。结果:HT组的BF、BV低于非HT组,而MTT、PS高于非HT组,差异均有统计学意义(t=-5.941,t=-5.777,t=5.863,t=6.954;P<005)。HT组的CTRP-3、LDL-C均低于非HT组,而MMP-9高于非HT组,差异均有统计学意义(t=-3.788,t=-5.835,t=6.935;P<0.05)。ROC曲线分析显示,BF、BV、MTT、PS、CT综合参数、CTRP-3、LDL-C及MMP-9诊断HT的AUC值分别为0.790、0.779、0.738、0.775、0.949、0.692、0.777和0.785;灵敏度分别为88.90%、100.00%、53.30%、66.70%、100.00%、88.90%、66.70%和78.60%;特异度分别为64.60%、51.60%、91.30%、77.60%、81.40%、47.80%、78.90%和75.80%;CT灌注图像参数与CTRP-3、LDL-C和MMP-9的AUC比较,差异均有统计学意义(Z=6.202,Z=4.563,Z=3.704;P<0.05)。结论:CT灌注成像参数及血清CTRP-3、LDL-C及MMP-9水平与ACI后HT具有密切关联,监测其变化程度有助于为预测ACI患者溶栓后发生HT提供重要参考依据。

益气固本汤联合西药治疗小儿肺肾阳虚型支气管哮喘的疗效及其对血清MMP-9、TIMP-1、IL-6、IL-8和免疫功能的影响

【目的】探讨益气固本汤治疗小儿肺肾阳虚型支气管哮喘的疗效及其对血清基质金属蛋白酶9(MMP-9)、基质金属蛋白酶组织抑制物1(TIMP-1)、白细胞介素6(IL-6)、白细胞介素8(IL-8)和免疫功能的影响。【方法】将124例肺肾阳虚型支气管哮喘患儿随机分为对照组和观察组,每组各62例。2组患儿均接受抗炎、平喘、吸氧等基础治疗,对照组同时给予孟鲁司特钠口服治疗,观察组在对照组的基础上加用益气固本汤治疗,疗程为28 d。观察2组患儿治疗前后哮喘症状积分、血清MMP-9、TIMP-1、IL-6、IL-8水平及免疫功能指标、肺功能指标的变化情况,并评价2组治疗方案的安全性。【结果】(1)治疗过程中,2组各有2例患儿脱落,最终各有60例患儿完成全部疗程的治疗。(2)治疗后,2组患儿的日间哮喘症状积分及晚间哮喘症状积分均较治疗前明显降低(P<0.05),且观察组对日间哮喘症状积分及晚间哮喘症状积分的降低作用均明显优于对照组(P<0.01)。(3)治疗后,2组患儿的用力肺活量(FVC)、第一秒用力呼气容积(FEV1)及FVE1/FVC等肺功能指标均较治疗前明显改善(P<0.05),且观察组对FVC、FVE1、FVE1/FVC等肺功能指标的改善作用均明显优于对照组(P<0.01)。(4)治疗后,2组患儿血清MMP-9水平均较治疗前降低(P<0.05),血清TIMP-1水平均较治疗前升高(P<0.05),且观察组对血清MMP-9水平的降低作用及对血清TIMP-1水平的升高作用均明显优于对照组(P<0.01)。(5)治疗后,2组患儿血清IL-6、IL-8水平均较治疗前明显降低(P<0.05),且观察组对血清IL-6、IL-8水平的降低作用均明显优于对照组(P<0.01)。(6)治疗后,2组患儿血清免疫球蛋白M(IgM)、免疫球蛋白G(IgG)、免疫球蛋白A(IgA)水平均较治疗前明显升高(P<0.05),且观察组对血清IgM、IgG、IgA水平的升高作用均明显优于对照组(P<0.01)。(7)治疗过程中,2组患儿均未发生明显不良反应,具有较高的安全性。【结论】益气固本汤联合西药治疗肺肾阳虚型支气管哮喘患儿疗效确切,可有效缓解患儿哮喘症状,减轻炎性反应,增强免疫功能,改善肺功能,且用药安全性较高。

固定正畸矫治80例病人唾液基质金属蛋白酶8和基质金属蛋白酶9的水平变化

目的 探究固定正畸矫治病人唾液基质金属蛋白酶8(MMP-8)、基质金属蛋白酶9(MMP-9)水平的变化及临床意义。方法 选取2019年6月至2021年12月于保定市第二医院接受固定正畸矫治成年病人80例及健康受试者40例为研究对象。对病人固定矫治前(T1)、固定矫治1周(T2)、固定矫治1个月(T3)及健康受试者探诊出血(BOP)、菌斑指数(PLI)进行检测;收集健康受试者及病人T1、T2、T3时期唾液,采用ELISA检测唾液中MMP-8、MMP-9水平;流式细胞术对唾液白细胞含量进行检测;分别对MMP-8、MMP-9与牙龈BOP相关性进行分析;分离唾液白细胞,检测白细胞MMP-8、MMP-9表达水平变化。结果T2、T3时病人BOP[(21.36±8.79)%、(13.06±5.80)%]、PLI[(2.53±0.43)分、(1.89±0.39)分]及唾液中MMP-8[(0.43±0.11)μg/L、(0.32±0.10)μg/L]、MMP-9[(3.64±0.76)μg/L、(2.02±0.50)μg/L]、白细胞水平[(17 893.71±505.49)个、(8 532.18±421.89)个],显著高于T1水平[(5.05±2.11)%、(0.71±0.25)分、(0.16±0.08)μg/L、(0.25±0.13)μg/L、(2 308.66±178.04)个,P<0.05];唾液MMP-8、MMP-9水平与牙龈BOP、PLI呈正相关;进一步发现T2、T3时白细胞MMP-8、MMP-9表达水平显著高于T1水平(P<0.05)。受试者操作特征(ROC)曲线显示唾液MMP-8及MMP-9水平能较好预测牙龈炎程度。结论 正畸病人唾液MMP-8、MMP-9水平与牙龈炎病情呈正相关,唾液MMP-8、MMP-9可作为评估正畸病人牙龈炎的潜在生物标志物。

大鼠神经元通过NLGN3/mTOR/MMP-9通路促进U251细胞迁移

目的:探讨肿瘤微环境中神经元对胶质瘤细胞迁移能力的影响。方法:分离培养胚胎18 d(E18)大鼠神经元,利用表达靶向神经连接蛋白3(NLGN3)分子shRNA的重组慢病毒(Lv-NLGN3-shRNA)感染神经元,real time RT-PCR和酶联免疫吸附试验(ELISA)检测NLGN3的表达,收集神经元培养上清与胶质瘤细胞系U251细胞共培养,Transwell实验检测U251细胞迁移能力,Western Blot方法检测U251细胞中哺乳动物雷帕霉素靶蛋白(mTOR)和基质金属蛋白酶-9(MMP-9)的表达。结果:Lv-NLGN3-shRNA重组慢病毒感染能够降低大鼠原代神经元中NLGN3 mRNA和蛋白的的表达,神经元培养上清与U251细胞共培养可以增加后者的迁移能力并上调mTOR和MMP-9的表达。然而,NLGN3表达被Lv-NLGN3-shRNA抑制后,培养上清对U251细胞促迁移能力下降,同时mTOR和MMP-9表达降低。结论:大鼠原代神经元可以通过NLGN3/mTOR/MMP-9信号通路增强U251细胞的迁移能力,这一途径可能是胶质瘤细胞转移的机制之一。

扶正化瘀通络方对高血压脑出血恢复期(气虚血瘀证)患者MMP-9、S100-β、AKT及Th1/Th2平衡的影响

【目的】观察扶正化瘀通络方治疗高血压脑出血恢复期气虚血瘀证患者的临床疗效及对血清基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)、S100-β蛋白(S100-βprotein,S100-β)、苏氨酸蛋白激酶(threonine protein kinase,AKT)和Th1/Th2平衡的影响。【方法】将130例高血压脑出血恢复期气虚血瘀证患者随机分为对照组和观察组,每组各65例。对照组给予西医常规治疗,观察组在对照组的基础上联合扶正化瘀通络方治疗,疗程为4周。观察2组患者治疗前后美国国立卫生研究院卒中量表(NIHSS)评分、健康状况调查简表(SF-36)评分、中医证候积分(主要症状包括乏力、偏瘫、口眼歪斜,次要症状包括头部刺痛、气短)及血清MMP-9、S100-β、AKT和白细胞介素10(IL-10)、超敏C反应蛋白(Hs-CRP)、同型半胱氨酸(Hcy)、白细胞介素6(IL-6)水平的变化情况,并评价2组患者的临床疗效。【结果】(1)治疗4周后,观察组的总有效率为95.38%(62/65),对照组为78.46%(51/65),组间比较,观察组的疗效明显优于对照组(P<0.05)。(2)治疗后,2组患者的NIHSS评分和中医证候积分均较治疗前明显降低(P<0.05),SF-36评分均较治疗前明显升高(P<0.05),且观察组对NIHSS评分和中医证候积分的降低幅度及对SF-36评分的升高幅度均明显优于对照组(P<0.05)。(3)治疗后,2组患者的血清MMP-9、S100-β、AKT水平均较治疗前明显降低(P<0.05),且观察组对血清MMP-9、S100-β、AKT水平的降低幅度均明显优于对照组(P<0.05)。(4)治疗后,2组患者血清Hs-CRP、Hcy、IL-6水平均较治疗前明显降低(P<0.05),血清IL-10水平均较治疗前明显升高(P<0.05),且观察组对血清Hs-CRP、Hcy、IL-6水平的降低幅度及对血清IL-10水平的升高幅度均明显优于对照组,差异均有统计学意义(P<0.05)。【结论】对于高血压脑出血恢复期气虚血瘀证患者而言,在西医常规治疗基础上联合扶正化瘀通络方治疗,可有效促进Th1/Th2平衡恢复,减轻氧化应激失衡,提高临床疗效。

Clinical significance of matrix metalloproteinase-9 expression in esophageal squamous cell carcinoma

AIM: To evaluate the expression of matrix metalloproteinase-9 (MMP-9) and its clinical significance in esophageal squamous cell carcinoma (ESCC). METHODS: The expression of MMP-9 in 208 cases of ESCC was detected by immunohistochemistry (IHC) and its clinical significance in ESCC especially the relationship with the clinicopathological parameters was analyzed. RESULTS: The percentage of positive cases for MMP-9 detected by IHC was 49.0%. MMP-9 was mainly expressed in the cytoplasm of cancer cells especially in the invasive front. Only weak expression was detected in the stromal cells and no expression in non-cancerous mucosa. The expression of MMP-9 was positively correlated with poorer differentiation (P= 0.001<0.01), existence of vessel permeation (P= 0.027<0.05) and lymph node metastasis (P=0.027<0.05). CONCLUSION: The expression of MMP-9 correlates with the cancer cell differentiation, vessel permeation and lymph node metastasis. It may be a novel biomarker for the diagnosis and treatment of ESCC.

High matrix metalloproteinase-9 expression induces angiogenesis and basement membrane degradation in stroke-prone spontaneously hypertensive rats after cerebral infarction

Basement membrane degradation and blood-brain barrier damage appear after cerebral infarc- tion, severely impacting neuronal and brain functioning; however, the underlying pathogenetic mechanisms remain poorly understood. In this study, we induced cerebral infarction in stroke- prone spontaneously hypertensive rats by intragastric administration of high-sodium water （1.3% NaC1） for 7 consecutive weeks. Immunohistochemical and immunofluorescence assays demonstrated that, compared with the non-infarcted contralateral hemisphere, stroke-prone spontaneously hypertensive rats on normal sodium intake and Wistar-Kyoto rats, matrix metalloproteinase-9 expression, the number of blood vessels with discontinuous collagen IV expression and microvessel density were significantly higher, and the number of continuous collagen IV-positive blood vessels was lower in the infarct border zones of stroke-prone sponta- neously hypertensive rats given high-sodium water. Linear correlation analysis showed matrix metalloproteinase-9 expression was positively correlated with the number of discontinuously collagen IV-labeled blood vessels and microvessel density in cerebral infarcts of stroke-prone spontaneously hypertensive rats. These results suggest that matrix metalloproteinase-9 upregula- tion is associated with increased regional angiogenesis and degradation of collagen IV, the major component of the basal lamina, in stroke-prone spontaneously hypertensive rats with high-sodi- um water-induced focal cerebral infarction.

Picroside Ⅱ down-regulates matrix metalloproteinase-9 expression following cerebral ischemia/reperfusion injury in rats

Studies have shown that Picroside Ⅱ attenuates inflammatory reactions following brain ischemia through the inhibition of the TLR-4-NF-KB signal transduction pathway, and ameliorates cerebral edema through the reduction of aquaporin-4 expression. Matrix metalloproteinase-9 （MMP-9）, located downstream of the TLR-4-NF-KB signal transduction pathway, can degrade the neurovascular matrix, damage the blood-brain barrier to induce cerebral edema, and directly result in neuronal apoptosis and brain injury, Therefore, the present study further observed MMP-9 expression in the brain tissues of rats with cerebral ischemia/reperfusion injury following Picroside Ⅱ treatment. Results demonstrated that Picroside Ⅱ significantly reduced MMP-9 expression in ischemic brain tissues, as well as neuronal apoptosis and brain infarct volume, suggesting Picroside Ⅱ exhibits neuroprotection by down-regulating MMP-9 expression and inhibiting cell apoptosis.

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.

Matrix metalloproteinase-9-1562C>T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer

AIM. To explore the role of the matrix metalloproteinase-9 （MMP-9） polymorphism in colorectal cancer （CRC） in a northeast Chinese population.METHODS： Genotyping of MNP-9-1562C〉T and 279R〉Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Multivariate logistic regression models were used to calculate adjusted odds ratios （OR） and 95% confidence intervals （95% CI）.RESULTS： The distribution of IVllVlP-9 -2562C〉T and 279 R〉Q genotype was not significantly associated with the risk of CRC. However, the risk of Ilymph node metastasis of CRC was increased in patients with the -1562T allele （OR = 2.601; 95% CI = 1.160-5.835; P = 0.022）. The frequency of MMP-9 279RR ＋ RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old （OR = 0.102, 95% CI = 0.013-0.812; P = 0.012）.CONCLUSION： Our results indicated that the MMP-9- 1562C〉T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer.

Huoxue Rongluo Tablet reduces matrix metalloproteinase-9 expression in infarcted brain tissue

Huoxue Rongluo Tablet was made of tall gastrodis tuber, dahurian angelica root, honeysuckle stem, grassleaf sweetflag rhizome, common flowering quince fruit, figwort root, red peony root and peach seed at a ratio of 3：2：6：2：3：3：3：3. Huoxue Rongluo Tablet is a well-established and common pre- scription for the treatment of cerebral infarction. In this study, a rat model of cerebral ischemia was established and the animals were intragastrically administered Huoxue Rongluo Tablet. This treat- ment reduced infarct volume, decreased matrix metalloproteinase-9 expression, and improved neurological function. Moreover, the effects of Huoxue Rongluo Tablet were better than those of buflomedil pyridoxal phosphate. These results indicate that Huoxue Rongluo Tablet is effective in treating cerebral infarction by regulating matrix metalloproteinase-9 protein expression.

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.

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.

Matrix metalloproteinase-9 expression and blood brain barrier permeability in the rat brain after cerebral ischemia/reperfusion injury

BACKGROUND： The integrity of the blood brain barrier （BBB） plays an important role in the patho-physiological process of cerebral ischemia/reperfusion injury. It has been recently observed that metalloproteinase-9 （MMP-9） is closely related to cerebral ischemia/reperfusion injury OBJECTIVE： This study was designed to observe MMP-9 expression in the rat brain after cerebral ischemia/reperfusion injury and to investigate its correlation to BBB permeability. DESIGN, TIME AND SETTING： This study, a randomized controlled animal experiment, was performed at the Institute of Neurobiology, Central South University between September 2005 and March 2006. MATERIALS： Ninety healthy male SD rats, aged 3-4 months, weighing 200-280 g, were used in the present study. Rabbit anti-rat MMP-9 polyclonal antibody （Boster, Wuhan, China） and Evans blue （Sigma, USA） were also used. METHODS： All rats were randomly divided into 9 groups with 10 rats in each group： normal control group, sham-operated group, and ischemia for 2 hours followed by reperfusion for 3, 6, 12 hours, 1, 2, 4 and 7 days groups. In the ischemia/reperfusion groups, rats were subjected to ischemia/reperfusion injury by suture occlusion of the right middle cerebral artery. In the sham-operated group, rats were merely subjected to vessel dissociation. In the normal control group, rats were not modeled. MAIN OUTCOME MEASURES： BBB permeability was assessed by determining the level of effusion of Evans blue. MMP-9 expression was detected by an immunohistochemical method. RESULTS： All 90 rats were included in the final analysis. BBB permeability alteration was closely correlated to ischemia/reperfusion time. BBB permeability began to increase at ischemia/reperfusion for 3 hours, then it gradually reached a peak level at ischemia/reperfusion for 1 day, and thereafter it gradually decreased. MMP-9 expression began to increase at ischemia/reperfusion for 3 hours, then gradually reached its peak level 2 days after perfusion, and thereafter it gradually decreased. CONCLUSION： MMP-9 expression increases in rat brain tissue after focal cerebral ischemia/reperfusion injury, which correlates with increased permeability of the BBB.

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.