Serum metalloproteinases MMP-2, MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in patients on hemodialysis

Background  

We assessed the effect of hemodialysis (HD) and chronic kidney disease (CKD) on the serum levels of metalloproteinase-2 (MMP-2), MMP-9 and metalloproteinase tissue inhibitors (TIMP-1) and TIMP-2.     

Serum matrix metalloproteinases MMP-2 and MMP-9 and metalloproteinase tissue inhibitors TIMP-1 and TIMP-2 in diabetic nephropathy

BACKGROUND: The regulation of mesangial extracellular matrix (ECM) turnover engages a number of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). High glucose concentration affects ECM degradation and the activities of MMPs and TIMPs. ECM accumulation is involved in the pathogenesis of diabetic nephropathy. METHODS: Serum MMP-9, MMP-2, TIMP-2 and TIMP-1 were measured with ELISA in patients with either chronic renal failure (CRF, n=20), type 2 diabetes mellitus (DM2, n=16) or diabetic nephropathy (DM2+CRF, n=14), and healthy controls (n=20). RESULTS: Diabetic nephropathy was related with profound decrease of serum TIMP-2 (122.2 +/- 47.2 vs. 263.0 +/- 89.2 ng/mL), TIMP-1 (242.5 +/- 96.9 vs. 347.4 +/- 87.2 ng/mL) and MMP-2 (385.4 +/- 42.6 vs. 517.2 +/- 75.4 ng/mL) (p<0.001). Both TIMP-1 and TIMP-2 were reduced in diabetic nephropathy in comparison with either diabetes alone (p<0.01 and p<0.001; respectively) or CRF alone (p<0.001 for both). An approximately 2-fold increase of MMP-9/TIMP-1 and MMP-2/TIMP-2 ratio was found in diabetic nephropathy when compared with diabetes with normal renal function (p<0.01). Further, in DM2 patients, TIMP-2 was decreased when compared with CRF alone (219.2 +/- 71.8 vs. 296.8 +/- 58.4 ng/mL). MMP-2 was lowered in both groups of DM2 and CRF patients (413.8 +/- 59.0 ng/mL and 409.7 +/- 93.1 ng/mL, vs. normal control value of 517.2 +/- 75.4 ng/mL; p<0.001). CONCLUSIONS: These data indicate that circulating TIMP-1, TIMP-2 and MMP-2 are decreased in patients with diabetic nephropathy when compared with either CRF or diabetes.     

MMP-2、MMP-9、TIMP-1在星形细胞瘤中的表达及其意义

目的：探讨基质金属蛋白酶（MMPs）中MMP－2、MMP－9及MMP－9的抑制剂TIMP－1在星形细胞瘤中表达的相互关系及其意义。方法：57例星形细胞瘤标本，其中I级星形细胞瘤11例，Ⅱ级星型细胞瘤16例，Ⅲ级星形细胞瘤17例，Ⅳ级星形细胞瘤13例。正常对照脑组织标本8例。计算平均阳性率。结果：低级别星形细胞瘤与高级别星形细胞瘤MMPs的表达差异有非常显著性（P＜0．01），而TIMPs的表达差异无显著性（P＞0．05）。结论：基质金属蛋白酶MMPs的表达与星形细胞瘤恶性程度密切相关。MMPs与TIMPs表达的平衡与星形细胞瘤恶性程度密切相关。     

自体静脉移植再狭窄与MMP-1、MMP-2及TIMP-2的表达

目的：通过测定自体静脉移植术后移植静脉管腔狭窄度、金属基质蛋白酶-1（MMP-1），MMP-2金属蛋白酶特异性抑制剂-2（TIMP-2）的表达，探讨自体静脉移植术后再狭窄与金属蛋白酶家族，（MMps）及其特异性抑制剂（TIMP）s的关系。方法：60只Wister大鼠均行颈静脉腹主动脉移植术，在术后28d后取出移植静脉行病理学检查测量移植静脉管腔狭窄度，根据移植静脉管腔狭窄程度，分成正常、轻、中、重4组，并采用免疫组织化学方法（ABC法）行MMP-1，MMP-2及TIMP-2的检测。结果：静脉移植后，移植静脉出现不同程度的狭窄。在狭窄的移植静脉， MMP-1、MMP-2和TIMP-2高水平表达；静脉狭窄程度越重，MMP-1、MMP-2和TIMP-2表达强度越高，MMP-1、MMP-2的升高幅度高于TIMP-2的升高幅度。结论：自体静脉移植术后移植血管再狭窄的发生和发展与MMPs及TIMPs的表达失衡密切相关。     

激素性股骨头坏死患者骨组织MMP-2、MMP-9、TIMP-1、TIMP-2蛋白的表达

目的观察激素性股骨头坏死患者股骨头骨组织中基质金属蛋白酶-2（MMP-2）、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）、基质金属蛋白酶组织抑制剂-2（TIMP-2）蛋白表达情况,探讨糖皮质激素对MMPs/TIMPs系统的影响,及其与股骨头坏死的相互关系。方法 2007年3月-2008年3月,取激素性股骨头坏死患者股骨头骨组织35例和股骨颈骨折患者股骨头骨组织21例,分别作为试验组和对照组。两组男女比例均为4：3;年龄41～70岁,其中试验组平均55.34岁,对照组平均55.33岁;试验组最近2年内接受过皮质激素治疗超过3周或超过1周的大剂量冲击治疗,对照组从未接受过超过1周的激素治疗。所有标本行多聚甲醛固定后石蜡包埋,HE染色及蛋白提取,采用蛋白免疫印迹（Westernblot）技术检测MMP-2、MMP-9、TIMP-1、TIMP-2蛋白的表达水平并求出MMPS/TIMPS比值。结果 HE染色：试验组未见完整的骨小梁和骨单位,可见不连续的骨碎片,碎片骨陷窝内骨细胞大部分消失,周围有大量炎性肉芽组织。对照组可见完整骨单位由板层骨构成,板层骨连续完整,围绕血管呈同心圆排列,小梁骨陷窝内可见骨细胞。Westernblot检测：激素组与对照组比较,MMP-2、MMP-9蛋白表达增高,TIMP-1、TIMP-2蛋白表达水平降低,差异有统计学意义（P〈0.05）。结论长期应用糖皮质激素致股骨头坏死的效应可能与其调控MMPs/TIMPs系统表达有关。     

The expression of MMP-2, MMP-7, MMP-9, and TIMP-1 in chronic rhinosinusitis and nasal polyposis

OBJECTIVES: To investigate the expression and clinical significance of MMP-2, MMP-7, MMP-9, and TIMP-1 in patients with nasal polyposis (NP) and chronic rhinosinusitis (CRS). STUDY DESIGN: Prospective study. SUBJECTS AND METHODS: This study involved 54 patients. There were three groups: nasal polyposis group, chronic rhinosinusitis group, and control group. Specimens were collected during endoscopic sinus surgery. Each sample was immunohistochemically examined. RESULTS: Expression of MMP-2 was found significantly increased in NP, whereas MMP-7 expression was found significantly increased in CRS (P < 0.001). TIMP-1 was significantly high in control group compared to CRS and NP (P < 0.001 and P = 0.002, respectively). CONCLUSIONS: Different regulation type of activation of MMPs has been found in these two diseases. If MMP-2 expression is intense in the mucosa, then this ends with polyp formation; if MMP-7 expression is intense, it ends with CRS or stays as CRS.     

Increased Plasma Matrix Metalloproteinase-2 (MMP-2), Tissue Inhibitor of Proteinase-1 (TIMP-1), TIMP-2, and Urine MMP-2 Concentrations Correlate With Proteinuria in Renal Transplant Recipients

Background

The most frequent cause of kidney allograft loss is chronic allograft injury, often with proteinuria as the clinical feature. Occurrence of proteinuria late after kidney transplantation is associated with worse graft function and patient survival.

Aim

The aim of the study was to assess plasma and urine matrix metalloproteinases (MMP-2 and MMP-9) and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in proteinuric renal transplant recipients (RTRs). The factors were determined by enzyme-linked immunosorbent assay in 150 RTRs (51 women and 99 men), aged 49.2 ± 11.5 years, at mean 73.4 ± 41.2 months after kidney transplantation (range: 12 to 240 months).

Results

Proteinuric RTRs compared with non-proteinuric RTRs had higher median plasma MMP-2 (P = .012), TIMP-1 (P = .0003), and TIMP-2 (P = .0021) concentrations, as well as higher urine MMP-2 (P < .0001) excretion. The presence of proteinuria had no impact on plasma MMP-9 and urine MMP-9, TIMP-1, and TIMP-2. Proteinuria and estimated daily proteinuria (uPr:uCr) correlated positively with plasma MMP-2 (r_s = 0.226, P = .0054 and r_s = 0.241, P = .003), TIMP-1 (r_s = 0.305, P = .00015 and r_s = 0.323, P = .000055), TIMP-2 (r_s = 0.273, P = .0007 and r_s = 0.269, P = .001) and urine MMP-2 (r_s = 0.464, P < .0001 and r_s = 0.487, P < .0001), respectively. Proteinuric RTRs had impaired graft function with higher median serum creatinine concentrations (1.91 [1.60–2.43] mg/dL versus 1.41 [1.20–1.65] mg/dL, P < .00001) and lower estimated glomerular filtration rate (36 [28–45] mL/min/1.73 m² versus 53 [43–61] mL/min/1.73 m², P < .00001) than RTRs without proteinuria.

Conclusions

Our research revealed that in RTRs, proteinuria was significantly associated with increased concentrations of enzymes involved in extracellular matrix (ECM) degradation: plasma MMP-2, TIMP-1, TIMP-2, and urine MMP-2. Findings strongly emphasize increased plasma TIMPs in proteinuric RTRs that inhibit degradation of ECM by MMPs and favor excessive deposition of ECM proteins.     

Anesthetic management in a child with Rolland-Desbuquois type dyssegmental dysplasia

A case of a 17-month-old boy with dissegmental dysplasia of the Rolland-Desbuquois type, who was scheduled for bilateral inguinal herniotomy, is presented. Preoperative assessment showed limited mouth opening, head extension, and kyphosis. Intubation with a size 4 mm endotracheal tube (ETT) was achieved with fiberoptic bronchoscopy, after which surgery proceeded uneventfully and the ETT was carefully removed. Copious airway secretions required frequent suctioning. On the second postoperative day, respiratory status stabilized, and the patient was discharged home.     

基质金属蛋白酶家族在骨关节炎软骨组织中表达的研究

[目的]观察骨关节炎关节软骨中MMP-7、MMP-9、MMP-13和TIMP-1的表达,探讨其与软骨退变的关系及可能的作用机制。[方法]选取20例因骨关节炎行关节置换的软骨组织,常规HE染色观察其组织学形态,ABC免疫组化法观察关节软骨MMP-7、MMP-9、MMP-13和TIMP-1的表达,2例因意外受伤截肢患者的正常膝关节软骨标本作为对照。统计采用Mann-Whitney U非参数检验及相关分析。[结果]骨关节炎关节软骨出现裂隙、纤维化,软骨细胞增多、排列紊乱,并出现大量簇聚软骨细胞和肥大软骨细胞。MMP-7和MMP-13在正常软骨全层均呈低表达,但在退变软骨中的表达则明显增多,光密度值行U检验,两组差异有显著性(P<0.01)。在正常与OA软骨的浅层,MMP-9和TIMP-1的表达无显著性差异(P>0.05);但在深层软骨中,OA软骨MMP-9和TIMP-1的表达较正常软骨明显增多,两组差异有显著性(P<0.01)。[结论]MMP-7,13在OA软骨全层表达均多于正常软骨;MMP-9,13仅在OA软骨深层出现过多表达。MMPs与TIMPs的失衡是导致关节软骨发生组织学退变的原因之一。     

MMP-2 and TIMP-1 are derived from, not in response to, pancreatic cancer.

INTRODUCTION: Genetic therapy aimed at disturbing the balance between matrix metalloproteinases (MMP) and their natural tissue inhibitors (TIMP) in treatment of pancreatic cancer requires an understanding of whether MMP and TIMP are tumor- or host-derived. This study was undertaken to determine whether production of MMP-2 and TIMP-1 is by, or in response to, pancreatic cancer. METHODS: PANC-1 (poorly differentiated human pancreatic cancer) or CD-1 (PANC cells transfected to overproduce TIMP-1) cells were implanted into the pancreata of 20 nude mice. After sacrifice, tumors and peritumoral stroma underwent immunohistochemical staining for human and murine MMP-2 and TIMP-1. Normal murine pancreas served as control. All stains were reviewed in a "blinded" manner by a pathologist and graded relative to normal control pancreata. RESULTS: Control pancreata displayed faint murine MMP-2 and TIMP-1 staining and no human MMP-2 or TIMP-1. MMP-2 was most prominent in peritumoral stroma, while TIMP-1 was most prominent in tumors. CD-1 tumors contained very high levels of TIMP-1 compared to PANC-1 tumors and control pancreata. Tumoral and peritumoral MMP-2 were overwhelmingly human. As well, tumoral TIMP-1 was predominantly human. CONCLUSIONS: In a murine model for human pancreatic cancer, nearly all TIMP-1 and MMP-2 expression is tumor-derived (i.e., human). Pharmacologic and gene therapy aimed at disturbing the MMP/TIMP balance in pancreatic cancer should be targeted toward tumor-specific mechanisms and warrants continued investigation.     

MMP-2和TIMP-2在大肠癌组织中的表达及其意义

目的探讨基质金属蛋白酶-2(MMP-2)和组织基质金属蛋白抑制剂-2(TIMP-2)在大肠癌组织中的表达及其意义。方法应用免疫组织化学SP法对60例大肠癌组织MMP-2和TIMP-2表达情况进行检测。结果MMP-2和TIMP-2在大肠癌组织中表达的阳性率分别为64.3%和30.3%。MMP-2的表达与大肠癌的病理分期和淋巴转移呈正相关(P<0.05),而TIMP-2的表达与其呈负相关,MMP-2和TIMP-2的表达呈负相关(P<0.05)。结论MMP-2和TIMP-2的表达与大肠癌的病理分期和淋巴转移密切相关,可作为判断大肠癌生物学行为的参考指标。     

beta2-microglobulin induces MMP-1 but not TIMP-1 expression in human synovial fibroblasts

BACKGROUND: beta2-Microglobulin (beta2m) amyloidosis is a destructive articular disease that causes significant morbidity in patients undergoing hemodialysis. The amyloid deposits contain beta2m, some of which is altered with advanced glycation end products (AGE-beta2m). The deposits are located principally in joint structures, with adjacent degradation of cartilage and bone. We hypothesized that one of the mechanisms by which beta2m induces joint destruction is to induce the release of matrix metalloproteinase-1 (MMP-1), but not tissue inhibitor of metalloproteinase-1 (TIMP-1), from synovial fibroblasts. METHODS: To test this hypothesis and determine the role of AGE-beta2m, we incubated human osteoarthritic synovial fibroblasts in the presence and absence of beta2m and AGE-beta2m and measured the release of interstitial collagenase (MMP-1) and/or TIMP-1 by enzyme-linked immunosorbent assay and Northern blot analysis. RESULTS: beta2m and AGE-beta2m at 10 and 25 microg/mL induced the release of MMP-1 from human osteoarthritic synovial fibroblasts at 24 hours. In contrast, there was no increased release of TIMP-1, leading to an increase in the MMP-1/TIMP-1 ratio indicative of uncontrolled collagenolysis. A similar dose response was observed at 48 hours, except that AGE-beta2m had no effect over control cultures. MMP-1 mRNA expression by Northern blot analysis paralleled these findings. The source of the fibroblasts did not alter the results. Finally, we demonstrated that doxycycline, a treatment for arthritis, can inhibit the release of MMP-1 from synovial fibroblasts incubated with beta2m. CONCLUSION: beta2m, at physiologically relevant concentrations, induces the release of MMP-1 without concomitant release of TIMP-1 from human synovial fibroblasts, leading to uncontrolled collagenolysis. The alteration of beta2m with AGE did not alter this effect at 24 hours, but blocked the effect at 48 hours. These findings may account for the tissue destruction seen in beta2m amyloidosis.     

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目的　探讨基质金属蛋白酶 2 (MMP 2 )、基质金属蛋白酶 9(MMP 9)和金属蛋白酶抑制因子 (TIMP 1)与结直肠癌术后肝转移的关系 ,评价其在预测结直肠癌肝转移中的作用。方法　 1997年 1～ 12月行结直肠癌根治术 59例 ,将组织石蜡块切片后 ,分别采用MMP 2、MMP 9和TIMP 1鼠单克隆抗体进行免疫组化染色。结果　结直肠癌术后肝转移率为 2 7 1%。转移组与未转移组MMP 9和TIMP 1两者相比差异有极显著意义 (P <0 0 0 1)。结论　对于预测结直肠癌手术后肝脏转移 ,MMP 9和TIMP 1有一定的价值 ,而三者联合应用可以提高诊断的灵敏度和特异度     

MMP-2、MMP-9及其抑制因子TIMP-2、TIMP-1在非黑色素性皮肤癌中的表达及意义

目的：分析MMP-2、MMP-9及其抑制因子TIMP-2、TIMP-1在非黑色素性皮肤癌中的表达情况及临床意义。方法：选取病理证实的SCC患者26例（SCC组）,BCC患者22例（BCC组）。手术切除病变组织,采用SABC法行免疫组化检测,记录各因子表达阳性率、染色强度和表达强度。同时,取20例正常皮肤为对照组。比较SCC组、BCC组患者及对照组各因子表达情况差异。结果：SCC组和BCC组与对照组MMP-2、MMP-9相比,表达阳性率、染色强度和表达强度显著增高,SCC组和BCC组与对照组TIMP-2、TIMP-1的表达阳性率、染色强度和表达强度明显降低（P〈0.05）。SCC组MMP-2、MMP-9的表达强度显著高于和BCC组,而TIMP-1、TIMP-2表达强度显著低于BCC组（P〈0.05）。结论：MMP-2、MMP-9及其抑制因子TIMP-2、TIMP-1与NMSC发生发展密切相关,其可能在NMSC侵袭与转移中发挥重要作用。     

基质金属蛋白酶-2及其组织抑制因子在大肠癌组织中表达及临床意义

目的 检测基质金属蛋白酶-2(MMP-2)及其组织抑制因子(TIMP-2)在大肠癌组织中的表达,探讨其临床意义.方法 采用免疫组织化学方法 、Western blot及实时定量PCR法检测50例大肠癌组织及其邻近的癌旁组织、50例正常大肠组织中MMP-2和TIMP-2的表达,并分析大肠癌组织中MMP-2和TIMP-2的表达与病理分级、临床分期及转移的关系.结果 大肠癌MMP-2蛋白阳性表达率为72.0%,显著高于癌旁组织的40.0%,正常组织的20.0%,呈递减趋势(P<0.01).TIMP-2蛋白阳性表达率在大肠癌为36.0%,显著低于癌旁组织的62.0%和正常组织的80.0%,呈递增趋势(P<0.01).Western blot结果 与免疫组织化学一致,灰度分析结果 显示差异有统计学意义(P<0.01).实时定量PCR结果 显示大肠癌MMP-2和TIMP-2扩增倍数值为(2.49±0.48)、(0.34±0.18),癌旁组织为(1.47±0.23)、(0.63±0.21),两组表达差异有统计学意义(P<0.01).大肠癌MMP-2的高表达和肿瘤分化程度、TNM分期、淋巴结转移呈正相关,而TIMP-2却相反.结论 大肠癌组织中MMP-2的高表达和TIMP-2的低表达,提示MMP-2和TIMP-2两者之间的平衡失调可能是肿瘤侵袭、转移的最终机制.     

MMP-2、MMP-9、TIMP-1在血管成形术后再狭窄中的表达及其意义的实验研究

目的观察PTA后MMP-2、MMP-9和TIMP-1在血管壁各层随时间的演变规律,探讨其在血管再狭窄过程中的表达及意义。方法48只大鼠制作成颈动脉再狭窄动物模型,选取30只内膜增生满意的标本,分别代表动脉损伤后1、3、7、14、28、42天6个观察时间点,对胶原纤维进行Masson染色。MMP-2、TIMP-1、PCNA进行免疫组织化学染色,MMP-9进行免疫组织化学和原位杂交两种染色。分析它们的表达与内膜增生和血管重塑的关系。结果正常血管不表达MMP-9mRNA及蛋白,损伤后第3天中膜、外膜mRNA表达达高峰,第7天内膜表达达高峰。MMP-9蛋白第7天内膜表达达高峰,且阳性细胞率高于中膜和外膜。第14、28天,血管壁各层表达逐渐下降至基线水平,内膜的阳性细胞主要集中在新生内膜靠近管腔的一侧。内膜MMP-2表达高峰出现晚至第14天,且近内弹力板处MMP-2也有明显的表达。正常血管壁不表达TIMP-1,损伤后第3天,中膜和外膜表达达高峰。第7天,新生内膜表达达高峰,中膜和外膜仍有较高水平表达。结论MMP-9、MMP-2、TIMP-1参与再狭窄,内膜MMP-9表达与早期增殖的细胞向内膜迁移形成新生内膜有关。MMP-2表达与晚期内膜形成、内膜重塑有关。TIMP-1的表达对内膜增生和重塑没有直接作用,其表达升高是机体为适应MMPs升高做出的代偿反应,在维持自身平衡中起作用。     

检测金属基质蛋白酶及其抑制物对判断膀胱癌浸润和转移的意义

目的　探讨金属基质蛋白酶 (MMP)及其抑制物检测在判断膀胱癌恶性度及预后中的作用。　方法　采用Westernblot和RT PCR方法 ,检测人膀胱肿瘤组织中MMP 2、MMP 9、TIMP 2蛋白表达和MMP 2、TIMP 2基因表达 ,应用计算机图像分析测定表达电泳条带的吸光度A值。　结果　膀胱肿瘤组织MMP 2、MMP 9、TIMP 2蛋白与基因表达与正常膀胱组织比较 ,差别有显著性意义 (P <0 .0 1) ;膀胱肿瘤组织TIMP 2蛋白与基因的吸光度A平均值与正常膀胱组织比较 ,差别无显著性意义 (P >0 .0 5 )。表浅膀胱癌组织的MMP 2 /TIMP 2蛋白、基因吸光度A平均值比率与正常膀胱组织比较 ,差别有显著性意义 (P <0 .0 5 ) ;浸润性膀胱癌的MMP 2 /TIMP 2蛋白、基因吸光度A平均值比率与正常膀胱组织相比 ,差别有显著性意义 (P <0 .0 1)。G2 、G3 与G1的MMP 2 /TIMP 2平均吸光度A值比率差别有显著性意义 (P <0 .0 1)。　结论　MMP 2、MMP 9表达和MMP 2 /TIMP 2比率对判断膀胱肿瘤浸润及转移有一定意义。检测MMP 2 /TIMP 2比率失衡较单纯检测MMP 2、TIMP 2的蛋白与基因表达更有意义     

MMP-9和TIMP-1在人结核性淋巴结中的表达及临床意义

目的探讨基质金属蛋白酶9(MMP9)及其组织抑制物(TIMP1)在人结核性淋巴结中的表达及其临床意义。方法免疫组化SP法检测MMP9和TIMP1蛋白在20例活动性淋巴结结核、20例陈旧性结核性淋巴结病灶和20例慢性非特异性淋巴结炎中的表达,采用图象分析技术对免疫组化结果进行定量分析。结果MMP9和TIMP1在三组淋巴结病变均有表达,其中MMP9在活动性淋巴结结核的肉芽肿、坏死周围炎性区呈强表达,在非特异性淋巴结炎和陈旧性结核病灶呈弱表达。MMP9,TIMP1及MMP9/TIMP1在活动性结核组表达显著高于非特异性淋巴结炎和陈旧性结核病灶(均为P<0.01),在单纯活动性淋巴结核组和合并活动性肺结核组表达无显著性差异(均为P>0.05)。结论MMP9、TIMP1高表达可能在结核性淋巴结炎发病机制中发挥重要作用,MMP9/TIMP1失衡可能预示疾病进展和结核播散。     

基质金属蛋白酶-9和组织金属蛋白酶抑制剂-1在骨肉瘤中的表达及其意义

目的　检测骨肉瘤组织中基质金属蛋白酶 (MMP) 9、组织金属蛋白酶抑制剂(TIMP) 1的表达 ,探讨它们与骨肉瘤侵袭的关系及临床意义。方法　对 70例骨肉瘤、15例骨软骨瘤和 15例正常骨组织进行免疫组织化学染色 ;对 60例病例随访资料进行生存分析。结果　MMP 9与TIMP 1在骨肉瘤中呈普遍阳性表达 ,明显高于骨软骨瘤及正常骨组织 ;MMP 9与TIMP 1的表达与肿瘤浸润软组织及预后存在相关性 ;MMP 9阳性而TIMP 1阴性者发生软组织浸润的比率高 ,预后差。结论　MMP 9、TIMP 1在骨肉瘤中呈普遍表达 ,可作为骨肉瘤侵袭的分子生物学标志和骨肉瘤诊断的辅助指标。MMP 9、TIMP 1的表达与骨肉瘤的软组织浸润有关 ,直接或间接影响患者的预后。     

膀胱癌组织MMP-9和TIMP-1的表达及其意义

目的　研究金属蛋白酶 9(MMP 9)及其抑制因子 (TIMP 1)在膀胱癌中的表达及其临床意义。方法　应用免疫组化方法检测MMP 9及TIMP 1在 6 5例膀胱癌和 19例非肿瘤性膀胱组织中的表达。结果　MMP 9在膀胱癌细胞和间质组织中均有表达 ,而TIMP 1主要表达在膀胱癌细胞中 ,在间质组织中很少表达。TIMP 1在膀胱癌细胞中的表达低于非肿瘤性膀胱组织中移行上皮的表达 ,两者差别有统计学意义 (P <0 .0 5 ) ,但与膀胱癌的病理分级、分期无统计学相关性 (P >0 .0 5 )。MMP 9在膀胱癌细胞及间质中的表达均高于非肿瘤性膀胱组织 ,两者差别有统计学意义 (P <0 .0 5 ) ,而且与膀胱癌的病理分级、分期均呈正相关 (P <0 .0 5 )。膀胱癌细胞表达TIMP 1与间质组织表达MMP 9呈负相关 (P <0 .0 5 ) ,MMP 9及TIMP 1的表达与肿瘤的复发、多发均无相关性 (P >0 .0 5 )。结论　MMP 9和TIMP 1参与膀胱癌的浸润和转移 ,对预后判断、诊断及治疗具有一定的意义。