Atorvastatin reduces myocardial fibrosis in a rat model with post- myocardial infarction heart failure by increasing the matrix metaHoproteinase-2/tissue matrix metalloproteinase inhibitor-2 ratio

Background The cholesterol-lowering statin drugs have some non-lipid-lowering effects, such as inhibiting myocardial remodeling. However, the underlying mechanism is still unclear. Methods The left anterior descending coronary artery was ligated to establish a rat model of heart failure, and the rats were divided into a sham operation （SO） group, myocardial infarction model （MI） group, and MI-atorvastatin group. Changes in hemodynamic parameters were recorded after the final drug administration. Histological diagnosis was made by reviewing hematoxylin and eosin （HE） stained tissue. Real-time quantitative polymerase chain reaction （PCR） was performed to determine the expressions of type I and type III collagen, matrix metalloproteinase-2 （MMP-2）, and tissue matrix metalloproteinase inhibitor-2 （TIMP-2）. Further, primary rat cardiac fibroblasts were cultured and the MTT assay was performed to determine the effect of atorvastatin on cardiac fibroblast proliferation. Results The model of heart failure was established and the results of HE staining and Masson＇s trichrome staining revealed that the rats in the heart failure group showed obvious hyperplasia of fibrotic tissue, which was significantly reduced in the atorvastatin group. Real-time quantitative PCR showed that the MI group showed a significantly increased expression of type I and type III coltagen, MMP-2, and TIMP-2, but a significantly reduced MMP-2/T＇IMP- 2 ratio. Compared with the MI group, the atorvastatin group showed significantly reduced expression of type I and III collagen, unchanged expression of MMP-2, significantly reduced expression of TIMP-2, and an increased MMP-2/ TIMP-2 ratio. We further found that atorvastatin significantly inhibited the Ang II-induced fibroblast proliferation and the expression of type I and type III collagen in cardiac fibroblasts while increasing the MMP-2/TIMP-2 ratio. Conclusions These data suggest that atorvastatin can inhibit cardiac fibroblast proliferation and enhance collagen degradation by increasing the MMP-2/TIMP-2 ratio, thereby inhibiting the formation of myocardial fibrosis in rats with heart failure after myocardial infarction.

Expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic stellate cells during rat hepatic fibrosis and its intervention by IL-10

AIM: To investigate the expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10).METHODS: Hepatic fibrosis was induced by CCl4administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8rats), CCl4-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type Ⅳ collagenase through portal vein catheter and the suspension was centrifuged by 11%Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with β-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h.RESULTS: Compared to group N in the 7th wk, MMP-2and TIMP-1 mRNA increased in group C (P= 0.001/0.001)and group I (P = 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P= 0.001/0.001). In the 11th wk, MMP-2 mRNAin group I was still lower than that in group C (P = 0.005),but both dropped compared with that in the 7th week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P= 0.001), and increased in group C (P = 0.001) while decreased in group I (P = 0.042)compared with that in the 7th wk. Same results were found by immunocytochemistry.CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.

Correlation of matrix metalloproteinase－2, －9, tissue inhibitor－1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The ex-pression of matrix metalloproteinase-2,-9 (MMP-2,MMP-9), tissue inhibitor-1 of matrix metalloprote inase(TIMP-1) , cell adhesion molecule 44 variant 6 (CD44v6) , HER2/neu and p53 was investigated in 154 pa-tients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP-2, MMP-9, TIMP-1,CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68. 18%, 98.05%,55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there wasclose positive relationship ( P < 0.05) between the expression of MMP-2 and MMP-9, TIMP-1 and CD44v6,HER2/neu and MMP-9, MMP-2 and p53. Up-regulation of MMP-2 was accompanied by advanced T stage( P < 0.01 ) . There was also a trend of MMP-2 expression being related with tumor metastasis. Increased ex-pression of HER2/neu was found in patients with tumor recurrence( P < 0.05 ) . The expression of TIMP-1 washigher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non-keratlnizing SCC than that in basaloid SCC ( P < 0.05 ) . These findings suggested that MMP-2 and MMP-9, HER2/neu andMMP-9, MMP-2 and p53 had a coordinate function in aggression of tumor; that MMP-2 had a more important function than MMP-9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker forpoor prognosis in HNSCC.

Imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 may contribute to hemorrhage in cerebellar arteriovenous malformations

In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy （control group）. Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-I, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

Expression of Matrix Metalloproteinase and Its Tissue Inhibitor in Haemangioma

The action mechanism of matrix metalloproteinases-2 （MMP-2） and tissue inhibitor of metalloproteinases-2 （TIMP-2） in the genesis, development and degeneration of haemangioma was investigated by detecting their expression in the tissue of haemangioma in different phases by using the immunohistochemistry. Fifty paraffin-embedded specimens of skin capillary haemangioma were collected, which were documented in the Department of Pathology, Renmin Hospital of Wuhan University from 2000 to 2006. All samples were stained by regular HE method, and proliferative cell nuclear antigen （PCNA） was tested by immunohistochemical S-P method. The samples were classified according to the Mulliken criteria and the expression pattern of PCNA. Immunohistochemical S-P method was ap- plied to detect the expression of MMP-2 and TIMP-2 in proliferative and degenerative phases of cutaneous capillary haemangioma, and in normal skin tissues. In combination with the detection of the expression of factor Ⅷ-related antigen, it was verified that in haemangioma tissues, the cells expressing MMP-2 and TIMP-2 were vascular endothelial cells. The MMP-2 and TIMP-2 expression was quantitatively analyzed by image analysis system （HPIAS-1000）, and one-way ANOVA（107） and SNK（q） test were done to analyze average absorbance （A） and positive area rate of immunohistochemically positive particles by using SPSS11.5. The results showed： （1） Among 50 samples of haemangioma, there were 26 proliferative haemangiomas, and 24 degenerative haemangiomas, respectively; （2） The expression of MMP-2 was weak in normal vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression of MMP-2 in proliferative group was significantly higher than in degenerative group and control group （normal skin） （P〈0.05）, but there was no statistically significant difference between the latter two groups; （3） TIMP-2 was highly expressed in normal tissues, degenerative vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression level of TIMP-2 in proliferative phase was significantly lower than in degenerative phase （P〈0.05）, and the expression of TIMP-2 in proliferative phase was significantly different from that in degenerative phase and normal tissues （P〈0.05）. It was concluded that in proliferative phase of haemangioma, MMP-2 may promote over-proliferation of endothelial cells of haemangioma, and in degenerative phase, TIMP-2 can inhibit the proliferation of endothelial cells of haemangioma. The two substances play important roles in the genesis, development and degeneration of haemangiomas.

血清MMP2/TIMP2比值与老年2型糖尿病患者并发AS的相关性分析

目的探讨血清基质金属蛋白酶-2/金属蛋白酶组织抑制因子-2(MMP2/TIMP2)比值与老年2型糖尿病(T2DM)患者并发主动脉硬化(AS)之间的关系。方法回顾性分析2022年1月至2023年4月万宁市人民医院收治的180例初次诊断为T2DM的老年患者的临床资料,并根据是否并发AS[颈动脉-股动脉脉搏波传导速度(cfPWV)>10 m/s]分为AS组(n=69)和非AS组(n=111)。另选取同时期来院体检健康者采用倾向性评分法匹配90例为对照组。比较3组对象的一般资料、实验室指标以及血清MMP2、TIMP2水平和MMP2/TIMP2比值。采用Spearman相关分析探究老年T2DM患者cfPWV与各项指标的相关性。采用多因素logistic回归模型分析,老年T2DM患者并发AS的影响因素。绘制受试者工作特征(ROC)曲线,分析并比较MMP2/TIMP2比值与多指标联合检测对老年T2DM患者并发AS的诊断价值。结果非AS组稳态模型胰岛素抵抗指数(HOMA-IR)、血清三酰甘油(TG)、MMP2水平及MMP2/TIMP2比值高于对照组,血清TIMP2水平低于对照组,差异有统计学意义(P<0.05)。AS组年龄、合并高血压比例高于非AS组(P<0.05)。AS组HOMA-IR、血清TG、MMP2水平及MMP2/TIMP2比值高于对照组和非AS组,血清TIMP2水平低于对照组和非AS组,差异均有统计学意义(P<0.05)。相关性分析结果显示,非AS组患者的cfPWV与HOMA-IR、TC、LDL-C、MMP2、MMP2/TIMP2比值呈正相关(r=0.217、0.264、0.216、0.197、0.703,P<0.05),与TIMP2呈负相关(r=-0.524,P<0.01);AS组患者cfPWV与MMP2、MMP2/TIMP2比值呈正相关(r=0.659、0.857,P<0.01),与TIMP2呈负相关(r=-0.532,P<0.01)。logistic回归分析显示,年龄增长(OR=1.108,95%CI:1.022~1.201,P=0.012)、高血压病(OR=2.877,95%CI:1.174~7.051,P=0.021)及MMP2/TIMP2比值升高(OR=5.147,95%CI:2.392~11.074,P<0.001)是老年T2DM患者并发AS的的独立危险因素。ROC曲线分析结果显示,MMP2/TIMP2比值及多指标联合检测诊断老年T2DM患者并发AS的曲线下面积分别为0.850(95%CI:0.789~0.899,P<0.01)和0.886(95%CI:0.831~0.929,P<0.01),灵敏度分别为73.91%、82.61%,特异度分别为89.19%、82.88%,约登指数分别为0.631、0.655。多指标联合检测的诊断效能明显大于MMP2/TIMP2比值,差异具有统计学意义(Z=2.233,P=0.026)。MMP2/TIMP2比值诊断老年T2DM患者并发AS的最佳截断值为3.23。结论MMP2/TIMP2比值升高为老年T2DM患者并发AS的独立危险因素,对老年T2DM并发AS的诊断有辅助价值,多指标联合检测可提高诊断效能。

Lichong decoction reduces Matrix Metalloproteinases-2 expression but increases Tissue Inhibitors of Matrix Metalloproteinases-2 ex-pression in a rat model of uterine leiomyoma

OBJECTIVE:To study the effect of Lichong decoction(LD) on expression of matrix metalloproteinase-2(MMP-2) and metalloproteinase-2(TIMP-2) in a rat model of uterine leiomyoma(UL).METHODS:UL was induced in rats using exogenous estrogen and progesterone.LD was administered(p.o.) for 4 weeks,and mifepristone(RU-486)used as a control.To observe the effect of LD on the uterine coefficient and uterine transverse diameter,a radioimmunoassay method was used to detect serum levels of sex hormones.Light microscopic analyses of pathologic changes in the tissues of UL rats were evaluated.Expression of the proteins of matrix metalloproteinases(MMPs) and tissue inhibitors of metalloproteinases(TIMPs) in uterine tissues was assessed by immunohistochemical staining and western blotting.RESULTS:A UL model in rats was established successfully.LD reduced uterine weight,uterine coefficient,and uterine transverse diameter compared with untreated controls.LD reduced levels of estradiol,progesterone,follicle-stimulating hormone,and luteinizing hormone in our UL models.LD improved the pathologic condition of uterine muscle.Expression of MMP-2 protein decreased to varying extents in LD-treated groups,but TIMP-2 levels were enhanced.LD appears to reduce MMP-2 expression and increase TIMP-2 expression in UL tissue.CONCLUSION:These data suggest that the mechanism of action of LD on ULs may involve reduction of MMP-2 expression and increase in TIMP-2 expression in rats.

Effects of benazepril on renal function and kidney expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in diabetic rats

Background Excessive deposition of extraceUular matrix （ECM） in the kidney is the hallmark of diabetic nephropathy. Increased matrix synthesis has been well documented but the effects of diabetes on degradative pathways, particularly in the in vivo setting. The renal protective effect of these pathways on matrix accumulation has not been fully elucidated. The present study was understaken to investigate the activity of matrix metalloproteinase-2 （MMP-2）, the expression of MMP-2 and tissue inhibitor of metalloproteinase-2 （TIMP-2） in kidney tissues of diabetic rats, and to explore the degradative pathway of type Ⅳ collagen （Ⅳ-C） and the renal protective effects of ACE inhibition- benazepril.

Effects of Saikosaponin-D on syndecan-2,matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 in rats with hepatocellular carcinoma

OBJECTIVE:To investigate effects of Saikosaponin D(SSd) on syndecan-2,matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinases-2(TIMP-2) in livers of rat with hepatocellular carcinoma(HCC).METHODS:Male SD rats were divided into control(n=10),model(n=20) and SSd(n=20) groups,and model and SSd groups given intragastric 0.2%(w/v) N-diethylnitrosamine to induce HCC.SSd group received 0.03%(w/v) SSd in saline.Liver samples were analysed immunohistochemically for syndecan-2,MMP-2,MMP-13 and TIMP-2 at 16 weeks.RESULTS:The model group had more malignant nodules than the SSd group;all model-group HCC cells were grade III;SSd-group HCC cells were grades I-II.Controls showed normal hepatic cell phenotypes and no syndecan-2 + staining.Syndecan-2 + staining was greater in the model group(35.2%,P≤0.001) than in controls or the SSd group(16.5%,P ≤ 0.001).The model group had more intense MMP-2 + staining than controls(0.37 vs 0.27,P≤0.01) or the SSd group(0.31 vs 0.37,P≤0.05);and higher MMP-13 + staining(72.55%) than in controls(12.55%,P≤0.001) and SSd group(20.18%,P≤0.01).The model group also had more TIMP-2 + staining(57.2%) than controls(20.9%,P≤0.001) and SSd group(22.7%,P≤0.001).Controls and SSd group showed no difference in TIMP-2 + rates.CONCLUSION:SSd inhibited HCC development,and downregulated expression of syndecan-2,MMP-2,MMP-13 and TIMP-2 in rat HCC liver tissue.

Effects of irbesartan on the expression of matrix metalloproteinase-2/ tissue inhibitor of metalloproteinase-2 in streptozotocin-induced diabetic rat kidney

Glomerular hypertrophy and progressive expansion of extracelluar matrix (ECM) have been regarded as the early feature of diabetic nephropathy (DN), which leads to accumulation of ECM and thickening of glomerular basement membrane, and subsequently induces renal fibrosis. Both increasing synthesis and decreasing degradation of matrix components are responsible for matrix accumulation. The later may play more important role in DN that involves a number of matrix metalloproteinases (MMPs). MMPs are a family of proteolytic enzymes whose activity is tightly regulated by tissue inhibitor of metalloproteinases (TIMPs), and the MMP/TIMP ratio is critical for coordinating matrix production and degradation. 1 Recently, considerable evidence suggests that the intrarenal renin-angiotensin system plays an important role in the development of DN. 2 Blockade of the renin-angiotensin system (RAS) by angiotensin-coverting enzyme inhibitor (ACEI) or angiotensin Ⅱ receptor antagonist (AIIRA) delays the progression of renal injury associated with diabetes. 3 AIIRA has been regarded as the first line choice for DN therapy. However, the potential mechanism for AIIRA in the ECM degradative pathway has not been fully elucidated. The present study is to investigate the effect of Irbesartan (Irb), a newly developed AIIRA, on renal expression of MMP-2 and TIMP-2 in streptozotocin (STZ)-induced diabetic rats.

Correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2

Background The relationship between the presence of metalloproteinases and thyroid cancer remains unknown, and many controversies still exist in this field. The objective of this study was to investigate the correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metall0Proteinase-2. Methods The correlations were studied bY detecting the levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloProteinase-1, and tissue inhibitor of metalloproteinase-2 by enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the peripheral blood of 30 patients with papillary thyroid carcinoma, 27 patients with benign thyroid disease, and 25 hea !hy vo!unteers. Results The leve!s of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood of patients with papillary thyroid carcinoma were significantly higher than those in the peripheral blood of patients with benign thyroid disease and healthy volunteers （P 〈0.05）. However, there were no significant differences between patients with benign thyroid disease and healthy volunteers （P 〉0.05）. The accuracy of detection by both enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the papillary thyroid cancer group was 83.33%. Conclusions The levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood are helpful in identifying thyroid carcinoma and aid in preoperative assessment.

Duodenal-jejunal bypass surgery on type 2 diabetic rats reduces the expression of matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in the thoracic aorta

Background Bariatric surgery offers a productive resolution of type 2 diabetes mellitus （T2DM）.The development of T2DM vasculopathy is due to chronic inflammation,which increases matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of matrix metalloproteinase-1 （TIMP-1） expression.This study sought to examine MMP-9 and TIMP-1 expression in the thoracic aorta after duodenal-jejunal bypass （DJB） surgery on a T2DM rat model induced by a high-fat diet and low dose streptozotocin （STZ）.Methods Twenty-one T2DM Wistar rats induced by high-fat diet and low dose STZ were randomly divided into DJB and sham duodenal-jejunal bypass （S-DJB） groups.Ten Wistar rats were fed a normal diet as a control.Recovery of gastrointestinal function post-operation and resumption of a normal diet completed the experiment.Body weight,blood glucose,blood lipid levels,and MMP-9 and TIMP-1 expression levels in aortic endothelial cells were measured throughout.Results DJB rats showed significant weight loss 2 weeks post-operation compared with S-DJB rats.After surgery,DJB rats showed significant improvement and steady glycemic control with improved insulin sensitivity and glucose tolerance.They also exhibited improved lipid metabolism with a decrease in fasting free fatty acids （FFAs） and triglycerides （all P ＜0.05）.Immunohistochemistry showed decreased MMP-9 and TIMP-1 expression 12 weeks after surgery （P ＜ 0.01）.Conclusions DJB surgery on an induced T2DM rat model improves blood glucose levels and lipids,following a high-fat diet and low dose STZ treatment.In addition,DJB decreased MMP-9 and TIMP-1 expression in vascular endothelial cells,which may play an important role in delaying the development of T2DM vascular disease.

血清TIMP-2、PLGF与高龄子痫前期患者胎儿生长受限的关系

目的 分析血清基质金属蛋白酶抑制因子(TIMP)-2、胎盘生长因子(PLGF)与高龄子痫前期(PE)患者发生胎儿生长受限(FGR)的关系。方法 采用前瞻性队列研究法选取2020年3月至2022年2月于新疆医科大学第一附属医院产检的138例高龄PE患者作为研究对象,纳入PE组;另选取同期在同一医院接受产检的138例高龄孕妇作为对照组。检查所有研究对象的肝肾功能[血肌酐(Scr)、谷丙转氨酶(ALT)、谷草转氨酶(AST)]、孕激素及血清TIMP-2、PLGF等。统计患者FGR发生情况,并分为FGR组和N-FGR组,采用Logistic回归分析血清TIMP-2、PLGF与高龄PE患者发生FGR的关系。结果 PE组血清TIMP-2水平高于对照组,血清PLGF水平低于对照组,差异均具有统计学意义(P<0.05)。138例高龄PE患者发生流产8例,胎停3例,退出研究2例,最终125例患者获得随访结果,胎儿娩出时确诊为FGR 27例。FGR组收缩压(SBP)、舒张压(DBP)、Scr及血清ALT、AST、TIMP-2水平均高于N-FGR组,血清PLGF水平低于N-FGR组,差异均具有统计学意义(P<0.05)。Logistic回归分析结果显示,血清TIMP-2高表达、PLGF低表达与高龄PE孕妇发生FGR有关(P<0.05)。结论 FGR患者血清TIMP-2显著升高,而PLGF水平显著降低;血清TIMP-2高表达、PLGF低表达是导致高龄PE孕妇FGR风险增加的危险因素。

重型颅脑损伤病人血清NF-L和TIMP-2水平变化及临床意义

目的探讨重型颅脑损伤(TBI)病人血清神经丝蛋白轻链多肽(NF-L)、组织基质金属蛋白酶抑制因子-2(TIMP-2的水平变化及临床意义。方法2019年8月~2021年8月前瞻性收集重型TBI共122例,采用酶联免疫吸附试验检查入院血清NF-1和TIMP-2水平;伤后6个月,应用GOS评分评估预后,其中4~5分为预后良好,1~3分为预后不良。结果伤后6个月,预后良好72例,预后不良50例。预后不良组血清NF-L以及TIMP-2水平明显高于预后良好组(P<0.05)。入院血清NF-L水平(r=-0.585)、TIMP-2水平(r=-0.542)与入院GCS评分呈明显负相关(P<0.05)。多因素Cox回归分析显示,血清NF-L、TIMP-2水平增高是重型TBI伤后6个月预后不良的独立危险因素(P<0.05)。ROC曲线分析显示血清NF-L1≥54.60 pg/ml联合血清TIMP-2≥42.59 ng/ml预测重型TBI伤后6个月预后不良的曲线下面积为0.854(95%CI 0.789~0.919),灵敏度为82.0%,特异度为70.8。结论重型TBI病人血清NF-L、TIMP-2水平明显增高,是伤后6个月预后不良的危险因素;两者联合应用对病人预后具有较高的预测价值。

葛根素对糖尿病大鼠肾功能及肾组织MMP-2与TIMP-2表达的影响

目的 探讨葛根素对糖尿病大鼠肾功能及肾组织基质金属蛋白酶 2 (MMP 2 )及其组织抑制剂 2 (TIMP 2 )表达的影响。方法 单侧肾切除大鼠ip链脲佐菌素诱发糖尿病模型。用原位杂交法检测肾小球MMP 2及TIMP 2mRNA表达 ,流式细胞术和免疫组织化学检测肾皮质TGFβ1,MMP 2 ,TIMP 2 ,IV型胶原及层粘连蛋白表达。 结果糖尿病组较对照组肾小球MMP 2mRNA及蛋白表达降低而TIMP 2mRNA及蛋白表达升高 ,TGFβ1,IV型胶原及层粘连蛋白表达亦增加 ,肾功能恶化 ;葛根素用药组较糖尿病组肾小球MMP 2mRNA及蛋白表达升高 ,而TGFβ1,TIMP 2 ,IV型胶原及层粘连蛋白表达减少 ,肾功能改善。结论 葛根素对糖尿病大鼠肾功能具有保护作用 ,除降低血糖外 ,调节肾小球MMP 2及TIMP 2表达 。

子宫颈腺癌中COX-2与p27^(kip1)、MMP-2蛋白表达的关系

目的探讨子宫颈腺癌组织中环氧化酶2(COX2)与细胞周期调控因子p27kip1、基质金属蛋白酶2(MMP2)的表达关系。方法采用组织微阵列技术结合免疫组化SP法检测106例子宫颈腺癌组织和22例慢性子宫颈炎组织中COX2与p27kip1、MMP2的表达。结果106例子宫颈腺癌组织COX2和MMP2的阳性表达率分别为86.8%和70.8%,均高于慢性子宫颈炎组织(P<0.01);p27kip1阳性表达率为58.5%,低于慢性子宫颈炎组织81.8%(P<0.05)。COX2和MMP2在子宫颈腺癌的病理分级中,G3组阳性表达率均明显高于G1组(P<0.05)。MMP2和p27kip1表达与子宫颈腺癌组织学类型有关,透明细胞腺癌MMP2阳性表达率高于子宫颈内膜腺癌和子宫内膜样腺癌(P<0.05),p27kip1阳性表达率低于子宫颈内膜腺癌和子宫内膜样腺癌(P<0.05)。COX2阳性表达强度与MMP2的阳性表达强度呈正相关(P<0.01)。COX2阳性表达强度与p27kip1的阳性表达强度呈负相关(P<0.05)。结论COX2与p27kip1、MMP2在子宫颈腺癌组织中的表达密切相关,p27kip1低表达与COX2、MMP2增强表达在子宫颈腺癌的发生发展中起重要作用,三者可能作为子宫颈腺癌恶性化的分子标志。

MMP-2、MMP-14、TIMP-2在胃癌组织中的表达及意义

目的探讨基质金属蛋白酶(matrix metalloproteinase,MMP)-2、14及基质金属蛋白酶组织抑制因子-2(tissueinhibitor of metalloproteinase,TIMP-2)在胃癌中的表达及其意义。方法用免疫组织化学方法(SP法)检测80例胃癌手术患者胃癌组织及30例同期癌旁≥5cm正常组织中MMP-2、MMP-14及TIMP-2的表达。结果①在胃癌、正常胃组织中,MMP-2阳性表达率分别为75.00%和36.67%,MMP-14阳性表达率分别为82.50%和33.33%,差异有统计学意义(均P<0.01);TIMP-2阳性表达率分别为45.00%和40.00%,差异无统计学意义。②癌组织中,MMP-2、MMP-14的表达与肿瘤分化程度、浸润深度、淋巴结有无转移和TNM临床分期密切相关(均P<0.01)。TIMP-2的表达仅与淋巴结有无转移相关(P<0.05)。③生存期<2年患者的MMP-2、MMP-14表达率明显高于生存期≥2年患者(均P<0.01)。结论胃癌组织中,MMP-2、MMP-14高表达,联合检测MMP-2、MMP-14或MMP-2、MMP-14、TIMP-2可作为胃癌恶性程度及预后判断的指标。

黄酒多酚对LDLR^(-/-)小鼠MMP-2、MMP-9、TIMP-1、TIMP-2表达和动脉粥样硬化斑块的影响

目的观察黄酒是否可以通过黄酒多酚发挥对动脉粥样硬化斑块的抑制作用并探讨其可能机制。方法40只6周龄雄性低密度脂蛋白受体敲除(LDLR-/-)小鼠,高脂饲料喂养诱导形成动脉粥样硬化模型,随机分为高脂对照组、瑞舒伐他汀组、黄酒多酚10 mg/(kg·d)组、黄酒多酚30 mg/(kg·d)组和黄酒多酚50 mg/(kg·d)组,每组8只,分别予以无菌水、10 mg/(kg·d)瑞舒伐他汀和10、30、50 mg/(kg·d)黄酒多酚干预。16周后处死小鼠,检测血脂,观察胸腹主动脉粥样硬化情况,Western blot测定胸主动脉组织内基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)、组织型基质金属蛋白酶抑制剂1(TIMP-1)及组织型基质金属蛋白酶抑制剂2(TIMP-2)的表达,明胶酶谱法测定主动脉弓动脉粥样硬化处MMP-2和MMP-9的活性。结果与高脂对照组相比,总胆固醇(TC)和低密度脂蛋白胆固醇(LDLC)在黄酒多酚组和瑞舒伐他汀组明显下降(P<0.01),甘油三酯(TG)在瑞舒伐他汀组明显下降(P<0.01),在黄酒多酚组差异不明显(P>0.05),在黄酒多酚组与瑞舒伐他汀组差异明显(P<0.05);5组间高密度脂蛋白胆固醇(HDLC)水平差异无统计学意义(P>0.05)。与高脂对照组相比,主动脉粥样硬化面积在瑞舒伐他汀组和黄酒多酚10、30、50 mg/(kg·d)组分别减少74.14%、18.51%、40.09%、38.42%(P<0.01),不同浓度黄酒多酚组主动脉粥样硬化面积与瑞舒伐他汀组比较差异显著(P<0.01)。黄酒多酚和瑞舒伐他汀均能明显抑制MMP-2、MMP-9的表达和活性(P<0.01),增强TIMP-1、TIMP-2的表达(P<0.01)。结论黄酒多酚具有类似瑞舒伐他汀的作用,能够调节血脂,在抑制MMP-2、MMP-9表达和活性的同时增强TIMP-1、TIMP-2的表达,减轻动脉粥样硬化斑块的形成,这可能是黄酒对心血管系统的保护机制之一。