羟苯磺酸钙对糖尿病大鼠肾小球MMP9/TIMP1的影响

目的 观察羟苯磺酸钙对糖尿病(DM)大鼠肾小球基质金属蛋白酶9(MMP9)、金属蛋白酶组织抑制因子1(TIMP1)、胶原Ⅳ以及肾小球基底膜超微结构的影响。方法 糖尿病模型由Spregue-Dawley(SD)大鼠单肾切除联合腹腔注射链脲佐菌素(STZ)诱导,糖尿病给药组(DD组)每天给予羟苯磺酸钙100mg／kg。12周后观察各组大鼠肾脏超微结构的改变以及免疫组化检查肾组织MMP9、TIMP1和胶原Ⅳ表达的变化。结果 12周后电镜检查显示DD组肾小球毛细血管基底膜增厚轻于糖尿病对照组(DM组),无胶原纤维的增生,内皮细胞孔距不及单肾切除对照组(NC组)均匀,但较DM组均匀,足细胞突起排列尚整齐,免疫组织化学显示DD组TIMP1、胶原Ⅳ明显低于DM组。结论 羟苯磺酸钙能抑制胶原Ⅳ过度积聚、减轻肾小球基底膜增厚,这可能与抑制糖尿病大鼠肾脏TIMP1表达、上调MMP9／TIMP1比值有关。     

糖基化终末产物对大鼠肾皮质基质金属蛋白酶2活性和表达的影响

的　研究糖基化终末产物 (AGEs)对肾皮质基质金属蛋白酶 2 (MMP 2 )活性及其mRNA表达的影响。方法　用链脲佐菌素制备大鼠糖尿病模型。大鼠血清蛋白与 0 .5mol/L葡萄糖孵育制备AGEs,分静脉注射AGEs(AGEs组 )、静脉注射大鼠正常血清 (阴性对照组 )和未注射大鼠 (对照组 ) 3组进行观察。ELISA测定肾皮质和血清AGEs含量 ,RT PCR检测MMP 2、金属蛋白酶组织抑制物 2 (TIMP 2 )mRNA表达水平 ,酶谱法测定MMP 2活性。结果　糖尿病大鼠肾皮质AGEs含量明显升高 ,MMP 2mRNA表达下降 ,TIMP 2mRNA表达上调 (均P <0 .0 1)。AGEs处理组大鼠肾皮质AGEs含量明显升高 (P <0 .0 1) ,MMP 2活性也明显下降 (均P <0 .0 5)。结论　AGEs通过降低大鼠肾皮质MMP 2的活性及其mRNA表达及增加TIMP 2mRNA表达 ,由此减少肾小球细胞外基质 (ECM )降解 ,可能是导致糖尿病肾病ECM积聚的原因之一     

基质金属蛋白酶在类似人类2型糖尿病大鼠肾病中的研究

目的 动态研究基质金属蛋白酶－2（MMP－2）和其体内特异的抑制物－金属蛋白酶组织抑制剂－2（TIMP－2）在类似人类2型糖尿病大鼠肾组织的改变。方法 利用免疫组织化学观察Ⅳ型胶原在肾小球的表达,酶谱法测定肾皮质MMP－2的活性,蛋白印迹法检测肾皮质TIMP－2的含量,Northern Blot观察肾皮质MMP－2和TIMP－2的基因表达。结果 类似人类2型糖尿病大鼠肾小球Ⅳ型胶原成分表达增强,肾皮质MMP－2基因表达减弱（P＜0．01）;其活性进行性减少（P＜0．0001）,而TIMP－2基因表达（P＜0．01）及其含量逐渐增加（P＜0．01）。结论 类似人类2型糖尿病大鼠肾组织MMP－2活性进行性降低、TIMP－2含量增加,两者比例失衡为肾小球ECM成份沉积的重要原因之一,基质降解减弱也参与了2型糖尿病大鼠肾脏病变的发生和发展。     

洛沙坦降低糖尿病大鼠肾组织膜3型基质金属蛋白酶mRNA的表达

目的　研究洛沙坦对糖尿病大鼠肾组织膜 3型基质金属蛋白酶 (MT3 MMP)mRNA表达的影响。方法　雄性Wistar大鼠分为 3组 ,A组 (11只 )为正常对照组 ,B组 (11只 )为糖尿病未干预组 ,C组 (9只 )为糖尿病大鼠洛沙坦 (血管紧张素Ⅱ 1型受体阻断剂 )干预组。以链脲佐菌素 (STZ)制备糖尿病大鼠模型。大鼠饲养 18周后取出肾脏检测MT3 MMPmRNA表达、电镜检测大鼠肾小球基底膜厚度及系膜基质密度 (系膜基质面积 /系膜面积 ) ;收集 2 4h尿测定尿白蛋白排泄量 (UAE)。mRNA表达采用RT PCR ,以 β actin作为内对照。UAE测定采用大鼠白蛋白特异的酶免疫分析试剂盒。结果　肾组织MT3 MMPmRNA表达在B组大鼠 (1.37± 0 .96 )显著高于A组 (0 .75± 0 .34,P <0 .0 5 )和C组 (0 .75± 0 .30 ,P <0 .0 5 ) ,而后两组比较差异无显著性。UAE、肾小球基底膜厚度及系膜基质密度在B组大鼠均显著高于A组和C组 (P <0 .0 5 )。结论　STZ糖尿病大鼠肾组织MT3 MMPmRNA表达明显增加 ,洛沙坦处理能延缓糖尿病肾病的发生 ,与此同时降低MT3 MMPmRNA表达。提示MT3 MMP与糖尿病肾病发病可能有一定关系。     

基质金属蛋白酶在大鼠心肌梗死模型心室重塑中的作用

目的:研究心肌梗死(MI)后基质金属蛋白酶2,9(MMP2,9)和组织金属蛋白酶抑制酶1(TIMP1)的变化规律,以及在左心室重塑过程中的作用。方法:通过结扎SD大鼠冠状动脉前降支建立MI模型。另设空白对照组、手术对照组。取MI术后第1天,术后1、2、4周各组心肌组织,采用免疫组化法测定其胶原含量和Ⅰ/Ⅲ胶原比例,酶谱法测定MI后MMP2,9活性蛋白的表达规律,WesternBlotting进一步确定酶谱法中所消化条带蛋白的属性,逆转录聚合酶链反应法(RTPCR)测定MI后MMP2、9和TIMP1mRNA的变化规律。结果:SD大鼠心肌内胶原含量在MI后第2、4周增加(P<0.01),Ⅰ/Ⅲ胶原比例同时期下降(P<0.05),MMP2、9蛋白水平和mRNA水平在MI后活性增强、表达增加,TIMP1蛋白含量减少。结论:SD大鼠MI后心肌组织内MMP2、9mRNA转录增加,TIMP1mRNA转录减少,MMP2、9活性增高和蛋白含量增加,TIMP1蛋白表达减少,胶原含量增加,Ⅰ/Ⅲ胶原比例下降,是参与心室重塑机制的重要组成部分。     

硫化氢通过调控转化生长因子-β及基质金属蛋白酶-9/基质金属蛋白酶抑制剂-1改善糖尿病大鼠肾小管间质纤维化

目的探讨硫化氢(H_2S)气体信号分子对糖尿病大鼠肾小管间质纤维化及转化生长因子(TGF)-β、基质金属蛋白酶(MMP)-9/基质金属蛋白酶抑制剂(TIMP)-1表达的影响。方法单次腹腔注射链脲佐菌素(STZ)建立糖尿病模型将成年雄性SD大鼠64只随机分为正常对照组(Control组)、STZ组、STZ+H_2S组、H_2S组。造模72 h后采尾静脉血检测,若血糖>16.7 mmol/L表明造模成功。H_2S组和STZ+H_2S组大鼠腹腔注射Na HS溶液100μmol·kg~(-1)·d~(-1),Control组和STZ组腹腔注射同等量生理盐水。8 w后取标本,Masson染色观察大鼠肾脏组织病理形态学改变,Western印迹检测大鼠肾脏TGF-β、MMP-9、TIMP-1、Ⅳ型胶原蛋白的表达水平。结果与Control组相比,STZ组存在明显肾小管间质纤维化,同时肾脏组织中Ⅳ型胶原、TGF-β、TIMP-1蛋白的表达升高,MMP-9蛋白的表达水平下降(P<0.05);与STZ组大鼠相比,STZ+H_2S组肾小管间质纤维化减轻,肾组织TGF-β、TIMP-1、Ⅳ型胶原蛋白的表达降低,MMP-9蛋白表达水平升高(P<0.05)。结论 H_2S可改善糖尿病大鼠肾小管间质纤维化,其机制可能与调控MMP-9/TIMP-1失衡以及TGF-β蛋白的表达水平有关。     

基质金属蛋白酶-9和金属蛋白酶组织抑制物-1在IgA肾病肾组织中的表达

目的 探讨基质金属蛋白酶－9（MMP－9）／金属蛋白酶组织抑制物－1（TIMP－1）系统在IgA肾病肾组织中的表达及其对IgA肾病的进展的影响。方法 采用免疫组织化学和原位杂交技术,分别在蛋白质和基因水平检测38例IgA肾病患者肾组织中的MMP－9和TIMP－1的变化。结果 MMP－9在正常肾脏肾小球的脏层上皮细胞和内皮细胞有少量表达,在肾小管上皮细胞和间质血管壁也有少量表达;在IgA肾病中,MMP－9在系膜增殖性肾小球和间质血管壁的表达均明显增多（P＜0．001）,而在硬化肾小球内的表达则明显减少,肾小管细胞的MMP－9表达无明显变化。TIMP－1在正常肾组织中不能检出,在IgA肾病患者具有系膜增殖性病变的肾小球中有微量表达,在增殖在很重但尚未完全硬化的肾小球内表达增多,在肾小管间质表达最为明显（P＜0．001）,其主要见于肾小管细胞、间质细胞和血管内皮细胞。肾组织中的TIMP－1表达与血清肌酐水平呈显著相关（P＜0．05）,与肾小管间质的纤维化和炎细胞浸润程度亦明显相关（P值均＜0．01）。肾小球中的MMP－9表达与尿蛋白无明显相关性,但与血清肌酐水平呈显著负相关（P＜0．05）。结论 MMP－9和TIMP－1的异常表达可能是影响IgA肾病进展的因素之一。     

基质金属蛋白酶/组织金属蛋白酶抑制物表达失衡在大鼠肾脏衰老过程中的意义

目的:探讨基质金属蛋白酶(MMPs)及其抑制物(TIMPs)在大鼠肾脏衰老过程中的作用。方法:选用3、12和24月龄大鼠，采用免疫组化技术分别检测基质金属蛋白酶—2、9(MMP—2、9)、组织金属蛋白酶抑制物—1、2(TIMP—1、2)、转化生长因子—β1(TGF—β1)等在不同月龄大鼠肾组织中的表达。结果TIMP—1、TIMP—2及TGF—β1主要表达在肾小球、肾小管、间质及血管，并随增龄表达增强(P＜O．01)；MMP—9、MMP—2主要表达在肾小管上皮细胞，随增龄表达无变化；TIMP—1与TGF—β1与肾小球硬化面积有相关性(r分别为O．751、O．771，P＜O．05)；TIMP—1与TIMP—2与小管间质纤维化面积有相关性(r分别为O．783、O．766，P＜O．O5)。结论:MMPs／TIMPs表达失衡在肾脏衰老过程中可能起重要作用。     

解聚复肾宁对糖尿病大鼠肾组织基质金属蛋白酶-9、金属蛋白酶组织抑制剂-1表达的影响

目的观察解聚复肾宁(JJFSN)对糖尿病(DM)大鼠肾组织基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)表达及肾脏保护作用机制。方法建立STZ诱导的DM SD大鼠模型,将成模DM大鼠随机分成4组:模型组、JJFSN组、厄贝沙坦组、JJFSN+厄贝沙坦组,同时设正常对照组。各组大鼠采用相应的干预措施处理12 w。检测各组大鼠第12周时肾重/体重、血糖、尿素氮、血肌酐、尿白蛋白排泄率(UAER),免疫组化法检测肾组织MMP-9、TIMP-1表达,透射电镜观察肾脏超微结构。结果模型组肾脏超微结构改变明显,血糖、UAER、尿素氮、血肌酐、肾重/体重显著增高。模型组大鼠肾组织TIMP-1的表达较正常对照组明显上调(P<0.01),JJFSN组、厄贝沙坦组、JJFSN+厄贝沙坦组肾组织TIMP-1表达明显下调(P<0.01),但仍高于正常对照组(P<0.01),JJFSN+厄贝沙坦组下调最明显(P<0.01)。DM模型组大鼠肾组织MMP-9的表达较正常对照组明显下调(P<0.01),解聚复肾宁组、厄贝沙坦组、解聚复肾宁+厄贝沙坦组肾组织MMP-9表达明显上调(P<0.01),但仍低于正常对照组(P<0.01),解聚复肾宁+厄贝沙坦组上调最明显(P<0.01)。结论 MMP-9、TIMP-l的表达变化与肾小球细胞外基质(ECM)降解减少相关,可能促进了糖尿病肾病(DN)的发生,JJFSN可能通过干预这种表达变化,减缓DN的发生和发展。     

棉酚对糖尿病大鼠肾脏转化生长因子β1和纤维连接蛋白及11β类固醇脱氢酶表达的影响

目的 观察棉酚对2型糖尿病大鼠肾脏病理变化影响,并探讨其作用机制. 方法 雄性SD大鼠随机分成正常组、糖尿肾病组及棉酚干预组.检测各组的血糖、胆固醇、低密度脂蛋白胆固醇水平;用光镜及电镜观察大鼠肾脏的组织形态学改变;反转录聚合酶链反应(RT-PCR)法检测肾脏组织转化生长因子β1(TGF-β1)、纤维连接蛋白(FN)、11β类固醇脱氢酶(11β-HSD1)、11β-HSD2mRNA含量;免疫组织化学法测定大鼠肾脏TGF-β1、FN表达水平. 结果 糖尿病组大鼠血糖、胆固醇、血低密度脂蛋白胆固醇水平高于正常组(P<0.01),肾小球体积增大,肾小球毛细血管基底膜不规则增厚,足细胞突起、肿胀,可见足突融合,阳性基质增多.肾组织TGF-β1、FN基因mRNA表达及蛋白表达高于正常组(P<0.01),11β-HSD2mRNA表达低于正常组(P<0.05);棉酚干预组血糖低于糖尿病组(P<0.01),血胆固醇、低密度脂蛋白胆固醇水平有下降趋势;肾脏组织病理改变减轻,TGF-β1、FNmRNA表达及蛋白低于糖尿病组(0.16±0.02、0.22±0.05和0.24±0.06、0.33±0.07,P<0.05),11β-HSD1、11β-HSD2mRNA表达与糖尿病组比较无明显改变. 结论 棉酚可改善2型糖尿病大鼠肾脏的病理改变,其作用机制与降血糖,进而抑制糖尿病大鼠肾脏TGF-β1、FN表达,阻止细胞外基质的堆积有关.     

糖尿病大鼠血红蛋白糖基化终产物与肾脏改变的关系及意义

目的　探讨糖尿病大鼠血红蛋白糖基化终末产物 (Hb AGE)与肾脏改变的关系。方法采用竞争性酶联免疫吸附分析法 (ELISA)检测 44只 12周和 2 8周病程的链脲佐菌素 (STZ) 糖尿病大鼠和 14只正常对照大鼠的Hb AGE含量 ,并测定尿蛋白 /肌酐 (Pr/Cr)比值及病程 2 8周时的肾小球基底膜厚度 (GBMT)。结果　随着病程的延长 ,Hb AGE水平显著增高 (P <0 .0 1) ,与血糖和HbA1c呈显著性正相关 ,但与HbA1c的关系更密切。Hb AGE与肾小球组织AGE(GTE AGE)含量呈显著性正相关 (r=0 .6 86 2 ,P <0 .0 1) ,二者与尿Pr/Cr比值和GBMT具显著相关性 ;胰岛素和氨基胍可降低Hb AGE水平 ,减少尿蛋白 ,阻止基底膜增厚。结论　Hb AGE可作为AGE循环标志物 ,反映慢性高血糖和肾小球AGE含量 ,有助于了解糖尿病时的肾脏改变 ,其水平长期增高可能是糖尿病肾病的一个危险因素。     

Extracellular matrix in human diabetic nephropathy: reduced expression of heparan sulphate in skin basement membrane

Summary In diabetic nephropathy, expression of glycosaminoglycan side chains of heparan sulphate proteoglycan in the glomerular basement membrane is reduced proportionally to the degree of proteinuria. We performed a cross-sectional study to evaluate whether non-vascular basement membranes also show a decrease in heparan sulphate side chain staining in patients with diabetic nephropathy. We evaluated the skin basement membrane for extracellular matrix components in the following groups: control subjects (n = 16); patients with Type 1 diabetes and normoalbuminuria (n = 17), microalbuminuria (n = 7), and macroalbuminuria (n = 16); patients with Type 1 diabetes and diabetic nephropathy undergoing renal replacement therapy (n = 13); and non-diabetic patients undergoing renal replacement therapy (n = 21). The following antibodies were used for this immunohistochemical study: monoclonal antibodies against the heparan sulphate side chain (JM403) and core protein (JM72) of the glomerular heparan sulphate proteoglycan; polyclonal antibodies against the core protein (B31); polyclonal antibodies against collagen types I, III, and IV, fibronectin, and laminin; and monoclonal antibodies against the non-collagenous domain of α1(collagen IV) and α3(collagen IV), against transforming growth factor β(2G7), and against advanced glycosylation end products (4G9). Expression of heparan sulphate side chains was reduced in the skin basement membrane of patients with overt diabetic nephropathy, of those with Type 1 diabetes undergoing renal replacement therapy, and those with non-diabetic renal failure. Increased intensity of staining was found for collagen type I and advanced glycosylation end products in patients with diabetic nephropathy. Changes in the extracellular matrix of the skin basement membrane seem to be similar to those in the glomerular basement membrane. These findings support the suggestion that patients with diabetic nephropathy also have altered heparan sulphate and collagen staining in extrarenal basement membranes. However, patients with non-diabetic renal failure also had reduced expression of heparan sulphate in the skin basement membrane, suggesting that this finding is not specific for diabetic nephropathy. [Diabetologia (1998) 41: 791–798] Received: 13 November 1997 and in revised form: 10 February 1998     

Mechanism of matrix accumulation and glomerulosclerosis in spontaneously hypertensive rats

BACKGROUND: Renal interstitial fibrosis and thickening of the glomerular basement membrane are associated with hypertension. However, the mechanism of matrix accumulation is unclear. Spontaneously hypertensive rats (SHR) develop hypertension at between 2 and 6 weeks of age. METHODS: To test the hypothesis that increased matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) contribute to the pathomechanisms of hypertensive nephropathy, the cortex and medulla of male SHR at 2 and 6 weeks were analyzed for MMP-2, MMP-7, and MMP-9 by gelatin and elastin gel zymography. The levels of TIMP-4 were measured by western blot analysis. The bands in blots were scanned and normalized with actin. To localize MMP-2 and TIMP-4 in situ, immuno-labeling was performed. To determine proteinuresis, urinary protein was measured by Bio-Rad dye binding assay. The mean arterial pressure (mmHg) was measured in Inactin-anesthetized rats by a PE-50 catheter in the femoral artery. Age-sex matched normotensive Wistar rats (NWR) were used as controls and grouped: (1). SHR, 2 weeks; (2). SHR, 6 weeks; (3). NWR, 2 weeks; and (4). NWR, 6 weeks (n = 6 in each group). RESULTS: Levels of cortex MMP-2 and MMP-9 were increased in 6 week SHR as compared with NWR. In the medulla, MMP-9 and MMP-7 were increased, but there was no change in MMP-2. The levels of cortex TIMP-4 tended to increase but insignificantly. In contrast, there were significant increases in the levels of TIMP-4 in the medulla of 6 week SHR as compared with 2 week SHR or NWR. In addition, there were substantial elastinolytic activity in the cortex of 6 week SHR. The in situ labeling suggested no TIMP-4 in the glomeruli. There was substantial TIMP-4 in the epithelial layer of tubules. The levels of fibrotic collagen were significantly higher in both the glomeruli and tubular interstitium. Urinary protein excretion was increased significantly in 6 week SHR when compared with other groups. The mean arterial pressure was 1.6-fold higher in 6 week SHR than in controls. CONCLUSION: These results suggest that increased MMP-2 and MMP-9 activity contributes to glomerular injury and hypertensive remodeling. The increased levels of TIMP-4 in the medulla may inhibit the collagenolytic activity of MMP but is unable to inhibit the elastinolytic activity. An important role of MMP-2, MMP-9, and TIMP-4 in hypertensive remodeling of the cortex and medulla in the SHR is demonstrated.     

Temporal Profile of Diabetic Nephropathy Pathologic Changes

Diabetic nephropathy, by far, is the most common cause of end stage renal disease in the US and many other countries. In type 1 diabetes, the natural history of diabetic nephropathy is tightly linked to evolution of classic lesions of the disease, namely glomerular basement membrane thickening, increased mesangial matrix, and reduced glomerular filtration surface density. These lesions progress in parallel and correlate with increased albumin excretion rate and reduced glomerular filtration rate across a wide range of renal function. In fact, the vast majority of the variances of albumin excretion and glomerular filtration rates can be explained by these glomerular lesions alone in type 1 diabetic patients. Although, classic lesions of diabetic nephropathy, indistinguishable from those of type 1 diabetes, also occur in type 2 diabetes, renal lesions are more heterogeneous in type 2 diabetic patients with some patients developing more advanced vascular or chronic tubulointerstitial lesions than diabetic glomerulopathy. More research biopsy longitudinal studies, especially in type 2 diabetic patients, are needed to better understand various pathways of renal injury in diabetic nephropathy.     

MMP-9/TIMP-1表达失衡与糖尿病大鼠皮肤"隐性损害"关系的初步探讨

目的 观察基质金属蛋白酶9(MMP-9)、组织金属蛋白酶抑制物1(TIMP-1)的表达和MMP-9/TIMP-1比值在糖尿病组和正常组大鼠皮肤表达的变化,并探讨其可能的作用.方法 采用链脲佐菌素制备糖尿病大鼠模型,6周后采用HE染色、免疫组织化学方法评估皮肤组织的组织学、细胞生物学行为的情况;通过逆转录-聚合酶链反应(RT-PCR)和Western印迹检测两组大鼠皮肤MMP-9、T1MP-1的表达情况.结果 与对照组比较,糖尿病组皮肤表皮厚度变薄,皮肤组织层次欠清晰、缺乏复层排列、明显萎缩,真皮纤维束排列紊乱、纤维间距增加、炎性细胞浸润.糖尿病组皮肤MMP-9的表达高于正常组,而TIMP-1的表达低于正常组,MMP-9/TIMP-1蛋白水平比值高于正常组.结论 糖尿病鼠皮肤在组织结构完整性未遭到破坏的情况下已经存在组织学、细胞生物学行为的改变,这种"隐性损害"可能与MMP-9/TIMP-1的平衡改变有关.     

糖尿病糖脂代谢紊乱与足细胞损害的实验研究

目的　观察糖脂代谢紊乱对糖尿病大鼠肾小球滤过屏障外层足细胞的影响 ,以探讨糖尿病肾病的发病机制。方法　采用链脲佐菌素诱导糖尿病大鼠模型 ,喂养 5周后 ,测定血糖、糖化血红蛋白、甘油三酯、总胆固醇、血肌酐、尿素氮和尿白蛋白排泄率 ,应用免疫组化检测肾小球足细胞损伤标志蛋白 -desmin的表达 ,同时利用透射电子显微镜观察肾小球足细胞超微结构。结果　糖尿病大鼠血糖、糖化血红蛋白、总胆固醇、血肌酐、尿素氮、尿白蛋白排泄率水平明显升高 (P <0 .0 5 ) ,肾小球内desmin蛋白表达上调 ,足细胞部分足突融合 ;同时 ,两组间血甘油三酯水平无显著性差异 (P >0 .0 5 )。结论　糖脂代谢紊乱可导致糖尿病大鼠肾小球滤过屏障外层足细胞明显损害 ,尿白蛋白排泄率增加 ,这可能是糖尿病肾脏损害、蛋白尿出现的机制之一     

Peripheral blood level alterations of TIMP-1, MMP-2 and MMP-9 in patients with type 1 diabetes.

AIM: To determine the plasma levels of enzymes and inhibitors involved in extracellular matrix turnover in patients with Type 1 diabetes with normal renal function. METHODS: Plasma levels of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were measured in 43 Type 1 diabetic subjects and age- and sex-matched controls. RESULTS: No significant difference in plasma MMP-2 between diabetic patients and controls was observed. MMP-9 was detected in the plasma of 15 diabetic patients (35%), but undetectable in all control subjects (P < 0.015). Plasma TIMP-1 concentrations were significantly elevated (P < 0.001) in diabetic patients compared to controls. There was no correlation observed between MMP-2, MMP-9 and TIMP-1 and similarly between MMP-2, MMP-9 and TIMP-1 and age, duration of diabetes, blood pressure and glycated haemoglobin (HbA1c). CONCLUSIONS: This study has demonstrated alterations in several plasma extracellular matrix modulators in the absence of significant vascular disease.     

肝复康对肝纤维化大鼠肝组织NF-κB、MMP-2和TIMP-2表达的影响

目的研究中药肝复康对肝纤维化大鼠肝脏NF-κB、基质金属蛋白酶-2（MMP-2）和金属蛋白酶组织抑制因子2（TIMP-2）基因表达的影响。方法随机将SD大鼠分为正常对照组、模型组、小剂量、中剂量和大剂量治疗组,制备CCl4肝纤维化模型,自第9周起,给予中药肝复康治疗至第20周。采用Western-Blot法检测NF-κB表达;采用RT-PCR法观察NF-κB、MMP-2和TIMP-2 mRNA水平。结果模型组大鼠肝组织NF-κB、MMP-2和TIMP-2表达增加,肝复康可明显抑制上述因子的表达（P〈0.01）,且三者mRNA水平在各组间呈显著正相关。结论肝复康治疗肝纤维化可能与其抑制NF-κB、MMP-2和TIMP-2的表达有关。