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1.
目的 观察慢性乙型病毒性肝炎(乙肝)和乙肝后肝硬化患者血清中的基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-2组织抑制因子(TIMP-2)和肝纤维化指标(HA、LN、ⅣC)及其相关性。方法 检测36例慢性乙肝、36例乙肝后肝硬化和20例对照组的血清MMP-2及TIMP-2,同时检测上述肝病患者血清肝纤维化指标。分析MMP-2、TIMP-2和肝纤维化指标之间的相关性。结果 慢性乙肝重度、肝硬化A级、B级、C级患者血清MMP-2、TIMP-2分别较对照组、慢性乙肝轻度、中度明显升高(P〈0.001);而慢性乙肝轻度、中度患者MMP-2、TIMP-2与对照组比较无显著性差异(P〉0.05)。慢性乙肝轻、中度之间MMP-2、TIMP-2比较无明显差异(P〉0.05)。血清MMP-2、TIMP-2水平分别与HA、LN、ⅣC有良好相关性;MMP-2与后三者的r值分别为0.928、0.909和0.826;TIMP-2与后三者的r值分别为0.688、0.556和0.644,P值均〈0.001。结论 TIMP-2、MMP-2在慢性肝病患者血清中明显升高,并且分别与肝纤维化血清学指标(HA、LN、ⅣC)有良好的相关性。MMP-2和TIMP-2可作为评价纤维化的指标之一。  相似文献   

2.
创面修复是一个复杂而有序的生物学过程,许多重要过程均受细胞因子和蛋白酶的调节。研究表明糖尿病患者足部伤口中基质金属蛋白酶(MMPs)表达增加,其抑制因子基质金属蛋白酶组织抑制因子(TIMPs)表达减少,导致伤口难以愈合。MMPs与TIMPs的比例可能比它们的绝对浓度更重要,是预测伤口愈合的重要指标,与伤口愈合时间呈负相关。局部应用强力霉素、一些含蛋白酶抑制剂的敷料以及促有丝分裂的牛血清提取物等均可通过抑制MMPs促进创面愈合。  相似文献   

3.
[目的]观察胃肠安方对人胃癌裸鼠原位移植瘤转移的抑制作用及其对基质金属蛋白酶9 (matrix metalloproteinase-9,MMP-9)、基质金属蛋白酶抑制因子(matrix metalloproteinases tissue inhibitor,TIMP)-1、TIMP-2蛋白表达的影响.[方法]建立裸小鼠胃原位癌模型,分为胃肠安方组及模型组,观察裸小鼠胃癌种植后肿瘤转移灶情况以及与肿瘤生长与转移密切相关的MMP-9、TIMP-1、TIMP-2的影响.[结果]胃肠安方能够抑制胃癌生长与转移,与模型组比较,差异具有统计学意义(P<0.05).胃肠安方组MMP-9蛋白阳性表达明显弱于模型组,TIMP-1及TIMP-2蛋白阳性表达明显强于模型组.[结论]胃肠安方具有抑制人胃癌裸鼠原位移植瘤转移作用,其抑制胃癌转移的部分作用机制与抑制MMP-9蛋白表达及上调TIMP-1、TIMP-2蛋白表达有关.  相似文献   

4.
目的 探讨再狭窄血管中基质金属蛋白酶(MMPs)与组织型基质金属蛋白酶抑制因子(TIMPs)的表达及益心方对其的影响.方法 制备大鼠血管再狭窄模型,采用不同浓度的益心方药物浓度干预,观察颈总动脉形态学改变,免疫组化法检测颈总动脉MMPs与TIMPs的表达.结果 假手术组血管内膜和中膜处均可见少量散在分布的MMP-2、MMP-9、TIMP-1和TIMP-2的阳性染色表达颗粒,以MMP-2表达最为明显;与假手术组比较,球囊导管内皮剥脱术后,模型组血管中MMP-2、MMP-9、TIMP-1和TIMP-2表达均显著增加(P<0.05或P<0.01),主要在新生内膜中表达,胞浆和基质内出现大量特异性的阳性颗粒;与模型组比较,益心方治疗低、高剂量组能明显抑制血管壁MMP-2、MMP-9的表达(P<0.05或P<0.01),其特异性的阳性颗粒与模型组相比显著减少,对TIMP-1和TIMP-2的表达也有减少的趋势.结论 益心方抑制血管再狭窄,其机制与抑制血管平滑肌细胞MMPs与TIMPs表达有关.  相似文献   

5.
背景:强力霉素对结肠癌细胞的分化和抑制作用已有报道,但其对胃癌细胞的作用尚未见报道。目的:观察强力霉素对人胃癌细胞SGC-7901的生长抑制作用及其对基质金属蛋白酶(MMP)-2和基质金属蛋白酶组织抑制因子(TIMP)-2表达的影响,探索胃癌治疗的新方法。方法:采用不同浓度的强力霉素作用于胃癌细胞SGC-7901,以噻唑蓝(MIT)法测定其细胞毒作用;逆转录聚合酶链反应(RT—PCR)法半定量测定MMP.2和TIMP-2mRNA的表达;免疫组化法观察MMP-2蛋白的表达。结果:强力霉素可抑制胃癌细胞SGC-7901的生长,具有浓度和时间依赖性(P〈0.01)。强力霉素可下调MMP-2mRNA和MMP-2蛋白的表达,上调TIMP-2mRNA的表达,具有浓度依赖性(P〈0.05)。结论:强力霉素能抑制胃癌细胞SGC-7901的生长,其作用机制可能与下调MMP-2表达、上调TIMP-2表达有关。  相似文献   

6.
目的评价血清基质金属蛋白酶-2(MMP-2)及其组织抑制因子-1(TIMP-1)水平与老年糖尿病足(DF)慢性溃疡的关系,探讨两指标的相关性。方法符合纳入标准的DF,≥60岁的52例患者作为老年DF组,60岁的36例为非老年DF组,30例非糖尿病的慢性溃疡患者为对照组(CON组)。应用ELISA法测定血清MMP-2、TIMP-1水平,并同时测定血脂、血糖等生化指标。结果 CON、非老年DF和老年DF三组血清MMP-2水平逐渐升高,分别为44.4(18.6)μg/L、59.1(18.2)μg/L和86.7(42.6)μg/L。两两比较差异具有统计学意义(P0.05);老年DF组血清TIMP-1水平低于其他两组,而非老年DF、CON组差异无统计学意义(P0.05)。血清TIMP-1、HbA1c、年龄及病程是MMP-2的独立影响因素。结论 DF血清MMP-2水平明显升高、TIMP-1水平下降,降低MMP-2水平可能会促进溃疡愈合。  相似文献   

7.
目的探讨2型糖尿病患者(T2DM)血清基质金属蛋白酶-2(MMP-2)及其组织抑制因子-1(TIMP-1)在糖尿病高血压、肾损害发病中的作用.方法随机收集T2DM患者64例,其中,无合并症者24例,合并高血压者20例,合并肾病者20例以及健康对照者24例.以ELISA法测定MMP-2、TIMP-1的含量.结果糖尿病患者尤其是合并高血压和肾病患者血清MMP-2明显低于健康对照组(P<0.01),并且随病情发展呈逐渐降低的趋势.而血清TIMP-1随病情的发展则呈现明显升高趋势,无合并症组、合并高血压组和合并肾病组TIMP-1水平明显高于健康对照组(分别为P<0.05,P<0.01和P<0.01).结论MMP-2和TIMP-1可能参与了糖尿病高血压、肾损害的发生发展过程,对其检测可能为糖尿病及其并发症的早期诊断和治疗提供新的依据.  相似文献   

8.
应用ELISA法测定20例糖尿病足溃疡并感染患者(DF组)、10例糖尿病非感染手术患者(DM组)、及10例非糖尿病非感染手术患者(NC组)创面渗液样本中MMP-2、TIMP-2的浓度,并进行相关分析。结果 DF组渗液中MMP-2浓度显著高于DM组及NC组(P<0.05);DF组渗液中TIMP-2浓度低于DM组及NC组(P<0.05);DF组MMP-2/TIMP-2比值明显高于DM组及NC组(P<0.01),而DM组与NC组之间的差异不具有统计学意义(P>0.05);DF分组中混合感染组MMP-2的浓度较单一感染组升高(P<0.05),两组间TIMP-2的浓度及MMP-2/TIMP-2比值差异没有统计学意义(P>0.05);Ⅲ级溃疡组MMP-2的浓度及MMP-2/TIMP-2比值较Ⅱ级溃疡组升高(P<0.05),两组间TIMP-2的浓度差异没有统计学意义(P>0.05)。结论糖尿病足溃疡合并感染创面中MMP-2的浓度明显升高,TIMP-2的浓度明显下降,MMP-2/TIMP-2比值明显升高。  相似文献   

9.
目的 观察慢性间断性缺氧(chronic intermittent hypoxia,CIH)对小鼠肾脏结构,基质金属蛋白酶-1、9(matrixmetallo-proteinase-1、9,MMP-1、9)及其组织抑制因子-1(tissue inhibitor of metalloproteinase-1,TIMP-1)表达变化的影响,探讨其在睡眠呼吸暂停综合征(sAs)肾损害中的作用。方法 将30只ICR小鼠随机分为4组,空气模拟对照组(10只)、CIH2周组(5只)、CIH4周组(5只)、CIH8周组(10只)。采用光镜下病理检查和免疫组织化学方法观察实验小鼠肾组织结构变化和MMP-1、MMP-9及TIMP-1在肾脏的表达。结果 ①CIH各组见肾小管上皮细胞肿胀、空泡、颗粒变性,随缺氧时间延长,变性范围扩大,主要表现为近曲小管的病理改变,其中8周组可见部分肾小管坏死。②MMP-1、MMP-9及TIMP-1主要表达于肾小管上皮细胞。③与对照组比较,CIH各组MMP-1表达均明显减少(P均d0.01),2周时降至最低,随后MMP-1表达略有回升;CIH组间两两比较差异无显著性(P〉0.05)。MMP-9在2周组的表达水平与对照组相比均显著升高(P〈0.01),而在4、8周两组则显著降低(P均d0.01)。CIH各组TIMP-1均呈高表达(P均〈0.01),其中高峰表达在2周缺氧组。CIH各组MMP-1/TIMP-1均显著降低(P均〈0.05),其中2周组达最低(P〈0.01),CIH各组间两两比较差异无显著性(P〉0.05)。MMP-9/TIMP-1随间断缺氧时间的延长呈下降趋势,CIH4周、8周两组均低于对照组(P〈0.05),最低表达在8周组(P〈0.01)。④随间断缺氧时间延长,TIMP-1与MMP-1之间存在负相关关系(r=-0.769,Pd0.01);TIMP-1与MMP-9之间存在正相关关系(r=0.392,PdO.05)。结论 CIH可引起实验小鼠肾小管变性、坏死等病理变化;同时肾小管上皮细胞MMP-1、MMP-9、TIMP-1表达异常;MMP-1/TIMP-1与MMP-9/TIMP-1下降,这可能参与了SAS肾损害的发生发展过程。  相似文献   

10.
肺纤维化的主要病理改变为肺成纤维细胞 (LF)聚积和细胞外基质 (ECM)积聚。LF在肺纤维化过程中有着重要的作用。LF几乎能合成全部有ECM降解活性的基质金属蛋白酶 (MMPs)及其抑制剂 (TIMPs) ,特别是TIMP 1 [1 ] ,当LF在静止状态下只能合成较低水平的TIMP 1 ,但其被激活后表达、合成并分泌大量的TIMP 1 ,阻止ECM的降解 ,特别是其中胶原的降解 ,从而促进肺纤维化的形成和发展。因此 ,我们将人的正义和反义TIMP 1 (hTIMP 1 )全长cDNA导入小鼠成纤维细胞 (NIH3T3细胞 )中以期观察其对N…  相似文献   

11.
目的:通过比较罗格列酮和辛伐他汀对兔动脉粥样硬化基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶抑制因子-2(TIMP-2)表达的影响,探讨罗格列酮抗动脉粥样硬化的作用机制。方法:将36只雄性新西兰兔随机分为对照组、模型组、辛伐他汀组和罗格列酮组;采用皮下注射同型半胱氨酸硫内酯及高脂饲养的方法建立兔动脉粥样硬化模型。检测血清氧化低密度脂蛋白(ox-LDL)、sCD40L水平和主动脉粥样硬化组织中MMP-2和TIMP-2的表达。结果:与对照组相比,其他3组MMP-2蛋白表达显著升高,而TIMP-2蛋白表达显著降低;与模型组比较,辛伐他汀和罗格列酮组MMP-2表达显著降低,TIMP-2表达显著增加,血清ox-LDL、sCD40L水平显著降低。辛伐他汀组和罗格列酮组比较,差异无统计学意义。结论:罗格列酮可通过下调兔主动脉粥样硬化组织中MMP-2、上调TIMP-2的表达,降低血清ox-LDL和sCD40L水平,减轻大动脉内膜的炎性反应,发挥抗动脉粥样硬化的作用。  相似文献   

12.
TIMP-1、MMP-2、MMP-9在大肠癌组织中表达的临床意义   总被引:1,自引:0,他引:1  
目的 研究TIMP-1、MMP-2和MMP-9在大肠癌组织中表达的临床意义.方法 采用免疫组化SP法检测50例大肠癌、10例正常大肠黏膜组织中TIMP-1、MMP-2和MMP-9的表达.结果 TIMP-1、MMP-2、MMP-9在正常组织中的表达均较低,而它们在大肠癌组织中阳性率均较高(P<0.05).结论 TIMP-1、MMP-2、MMP-9与大肠癌临床病理参数有关系.TIMP-1、MMP-2和MMP-9可能是大肠癌侵袭转移的分子标记物.  相似文献   

13.
目的:研究基质金属蛋白酶2(MMP-2)及金属蛋白酶抑制剂-2(TIMP-2)表达在胃癌、肠癌转移及预后判断中的作用。方法:采用逆转录荧光实时定量PCR的方法检测58例结肠癌患者,52例胃癌患者外周血中MMP-2和TIMP-2 mRNA的表达水平。结果:胃癌、肠癌患者MMP-2表达均高于正常对照(P〈0.01);其中,有局部浸润、淋巴结肿大、远处脏器转移者的MMP-2 mRNA和TIMP-2/MMP-2比值与未转移者差异有统计学意义(P〈0.01);TIMP-2/MMP-2比值对判断胃癌、肠癌瘤转移的灵敏度分别为86.6%、89.2%,特异性为81.8%、83.3%。结论:基质金属蛋白酶2的表达升高与恶性肿瘤的转移密切相关,TIMP-2/MMP-2比值是恶性肿瘤转移和预后判断的良好指标。  相似文献   

14.
Background. A 1 cm margin seen at operation is typically the minimally acceptable margin for liver resections. Patients who fail to achieve this margin are routinely treated with edge cryotherapy at our unit. This paper aims to assess the benefit of edge cryotherapy on survival in patients with such suboptimal margins. Patients and methods. Between January 1990 and February 2006, 608 patients underwent liver resection and/or cryotherapy for colorectal cancer metastases. All liver resections were performed using the CUSA transection method. Data on marginal status were available for 398 patients. Patient demographics, number and size of liver lesions, preoperative and postoperative carcinoembryonic antigen (CEA), extent of liver resection, margin status, site and date of recurrence, date of last follow-up and death were examined. Results. There were 175 patients in the R0 group (>1 cm macroscopic and ≥1 mm microscopic margin), 103 patients in the R1 group (>1 cm macroscopic and <1 mm microscopic margin) and 120 patients in the R2 group (≤1 cm macroscopic margin and received edge cryotherapy). After a median follow-up of 63 months, there were no significant difference between the 5-year survival rates for R0, R1 and R2 (40%, 30% and 28%, respectively). Conclusion. As long as the surgical margin is clear macroscopically, the microscopic margin width does not affect survival. In patients with suboptimal margins, the addition of edge cryotherapy improves the prospect for long-term survival and may lower recurrence risk.  相似文献   

15.
The optimal treatment for recurrent lesions after hepatectomy for colorectal liver metastases is controversial. We report the outcome of aggressive surgery for recurrent disease after the initial hepatectomy and the influence on quality of life of such treatment. Forty-five (70%) of the 64 surviving patients developed recurrence after the initial hepatectomy for liver metastases. The determinants of hepatic recurrence were the distribution and the number of liver metastases. Twenty-eight (62%) of patients with recurrence underwent resection. A second hepatectomy was performed in 20 patients, and a third hepatectomy was done in 5 patients. Ten patients with pulmonary metastasis underwent partial lung resection on 14 occasions, while resection of brain metastases was performed in 3 patients on 5 occasions. There were no operative deaths after resection of recurrent disease. The morbidity rate was 28% after repeat hepatectomy, 21% after pulmonary resection, and 0% after resection of brain metastasis. The Karnofsky performance status (PS) after the last surgery was not significantly different from that after the initial hepatectomy. The 3- and 5-year survival rates after the second hepatectomy were 54% and 14%, respectively. The 3-and 5-year survival rates of the patients undergoing resection of extrahepatic recurrence were both 17%. The survival rate after resection of recurrent disease (n=28) was significantly better than that of patients (n=17) with unresectable recurrence (P < 0.05). For the 66 patients with colorectal liver metastases, the 5-year survival rate after initial hepatectomy was 50%. The distribution and the number of liver metastases and the presence of extrahepatic disease, as single factors, significantly affected prognosis after the initial hepatectomy. Multivariate analysis revealed that only the presence of extrahepatic metastasis and a disease-free interval of less than 6 months were independent predictors of survival after the initial and second hepatectomy, respectively. It is concluded that aggressive surgery is an effective strategy for selected patients with recurrence after initial hepatectomy. Careful selection of candidates for repeat surgery will yield increased clinical benefit, including long-term survival.  相似文献   

16.
Objective: The aim of this study was to evaluate the accuracy of intra‐operative ultrasound (IOUS) imaging in detecting liver secondaries at the time of primary colorectal surgery and to evaluate the impact of IOUS on patient management. Methods: Data from 167 patients with primary colorectal cancer who were admitted for elective surgery between January 1995 and December 2003 were prospectively evaluated and analysed. All patients underwent pre‐operative abdominal ultrasonography (US) and computed tomography (CT), as well as IOUS. The final diagnosis of liver metastases was made by means of histological examination of either biopsy or surgical specimens. The sensitivities of pre‐operative US and CT were compared with the sensitivity of IOUS, referred to histology. Changes in surgical management owing to IOUS findings were noted. Results: IOUS supplied additional information in the case of 31 patients. In 28 of these patients, this information had a major impact on the intra‐operative strategy, in that the procedure was altered. Conclusions: IOUS is safe, simple to perform and more accurate than pre‐operative imaging. It reduces the number of patients subjected to superfluous surgery. The use of IOUS is therefore encouraged during colorectal cancer surgery.  相似文献   

17.
18.
目的:观察STZ鼠肾组织及高糖状态下正常人类系膜细胞(NHMC)中金属基质蛋白酶9(MMP-9)、金属基质蛋白酶组织抑制物1(TIMP-1)表达状况及磷酸肌酸激酶(PKC)抑制剂对其表达的影响,探讨糖尿病肾病(DN)时PKC抑制剂在细胞外基质降解中的作用。方法:Wistar大鼠随机分为正常对照组、DN模型组、PKC抑制剂组。PKC抑制剂组采用根皮素10mg/(kg.d)混悬液灌胃进行干预。第8周处死大鼠(每组6只)。检测24h尿蛋白定量、血肌酐水平。用免疫组化方法检测肾脏组织MMP-9、TIMP-1的表达。用ELISA方法检测肾脏组织PKC活性。体外实验,将NHMC置37℃,5%CO2培养箱中进行培养。并将NHMC分为N组(对照组):糖浓度5mmol/L,H组(高糖组):糖浓度30mmol/L,P组(高糖加PKC抑制剂):糖浓度30mmol/L加chelery thrine chloride 10-5mmol/L,M组(甘露醇组):甘露醇30mmol/L。于培养24、48、72h后用MTT法测定细胞增值。采用ELISA方法检测四组PKC活性。分别用RT-PCR及Western Blot检测各组MMP-9、TIMP-1mRNA及蛋白表达。结果:DN模型组尿蛋白排泄明显增加(P<0.01),血肌酐上升(P<0.05),PKC活性明显增高,MMP-9和TIMP-1出现表达,MMP-9/TIMP-1比值降低。PKC抑制剂干预后其尿蛋白排泄明显减少,血肌酐水平降低,PKC活性下降,MMP-9、TIMP-1表达上调,其MMP-9/TIMP-1比值增高。体外实验中,高糖能促进NHMC增殖,且NHMC的增殖状况随时间的递增而明显增加。高糖(30mmol/L)能增加系膜细胞PKC的活性,MMP-9、TIMP-1较高表达,MMP-9/TIMP-1比值降低。而PKC抑制剂使PKC的活性降低同时,MMP-9、TIMP-1表达上调,MMP-9/TIMP-1比值增高。结论:高糖可诱导PKC活性,PKC抑制剂能使MMP-9、TIMP-1表达上调,MMP-9/TIMP-1表达比值升高,推测PKC的活性状况可影响DN细胞外基质降解过程。  相似文献   

19.
Seven (3.3%) of 213 patients who underwent surgery for early colorectal cancer (invasion limited to no deeper than the submucosa) at the National Cancer Center Hospital, Tokyo, between 1986 and 1995 had synchronous (2 patients) or metachronous (5 patients) liver metastases. The average period from surgical resection of the primary colorectal cancer to the diagnosis of liver metastases was 25 months (range, 0–52 months). The clinicopathologic and immunohistochemical features of the primary lesions in these patients were compared with these features in the lesions in consecutive patients with early colorectal cancer who had no evidence of liver metastases within at least 5 years after colorectal resection. Venous invasion was more frequent in the primary lesions with liver metastases than in those without liver metastases (57% vs 0%; P = 0.0035). Expression of p53 and CD44v9 was more frequent in the primary lesions with liver metastases (71% and 100%) than in those without metastases (56% and 72%). In contrast, MUC2 expression was more frequent in the primary lesions without liver metastases (72%) than in those with metastases (43%). Venous invasion is considered to be closely related to liver metastasis, and the immunohistochemical expression of p53 and CD44v9 provides useful information for identifying those patients with early colorectal cancer who have a high risk of developing liver metastases. Received: June 16, 1998/Accepted: October 23, 1998  相似文献   

20.

Background:

Traditionally a 1-cm margin has been accepted as the gold standard for resection of colorectal liver metastases. Evidence is emerging that a lesser margin may provide equally acceptable outcomes, but a critical margin, below which recurrence is higher and survival poorer, has not been universally agreed. In a recent publication, we reported peri-operative morbidity and clear margin as the two independent prognostic factors. The aim of the current study was to further analyse the effect of the width of the surgical margin on patient survival to determine whether a margin of 1 mm is adequate.

Methods:

Two hundred and sixty-one consecutive primary liver resections for colorectal metastases were analysed from 1992 to 2007. The resection margins were assessed by microscopic examination of paraffin sections. The initial analysis was performed on five groups according to the resection margins: involved margin, 0–1 mm, >1–<4 mm, 4–<10 mm and ≥ 10 mm. Subsequent analysis was based on two groups: margin <1 mm and >1 mm.

Results:

With a median follow-up of 4.7 years, the overall 5-year patient and disease-free survival were 38% and 22%, respectively. There was no significant difference in patient- or disease-free survival between the three groups with resection margins >1 mm. When a comparison was made between patients with resection margins ≤1 mm and patients with resection margins >1 mm, there was a significant 5-year patient survival difference of 25% versus 43% (P < 0.04). However, the disease-free survival difference did not reach statistical significance (P= 0.14).

Conclusions:

In this cohort of patients, we have demonstrated that a resection margin of greater than 1 mm is associated with significantly improved 5-year overall survival, compared with involved margins or margins less than or equal to 1 mm. The possible beneficial effect of greater margins beyond 1 mm could not be demonstrated.  相似文献   

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