解聚复肾宁对糖尿病大鼠肾CTGF、MMP-9及TIMP-1的影响

目的 探讨解聚复肾宁(JJFSN)对糖尿病(DM)大鼠肾组织结缔组织生长因子(CTGF)、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 复制STZ诱导的糖尿病SD大鼠模型,将成模DM大鼠随机分成4组:DM模型组、解聚复肾宁组、厄贝沙坦组、解聚复肾宁+厄贝沙坦组,设正常对照组.干预措施处理12周,常规方法检测各组大鼠第12周时血糖、尿素氮、血肌酐、尿白蛋白排泄率(UAER),免疫组织化学法检测肾组织MMP-9、TIMP-1表达,免疫荧光法检测肾组织CTGF表达.结果 DM模型组血糖、UAER、尿素氮、血肌酐显著增高,肾组织CTGF、TIMP-1的表达较正常对照组明显上调(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CTGF、T1MP-1表达明显下调(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).结论 CTGF、MMP-9、TIMP-1的表达变化与肾小球细胞外基质(ECM)降解减少相关,可能促进糖尿病肾病的发生,JJFSN可能通过干预这种表达变化减缓糖尿病肾病的发生和发展.     

TGF-β1与CTGF在RA-ILD患者血清中的表达水平及意义

目的通过检测TCF-β1和CTGF在RA-ILD患者血清中的表达水平,探讨其在RA—ILD中的意义。方法采用ELISA法检测100例RA（包括45例RA-ILD）和30例健康体检者血清TGF-β1、CTGF的表达水平。结果RA-ILD组中TGF-β1、CTGF、CRP、RF的含量分别为（15．9±4．5）ng／mL、（77．97±34．04）ng／mL、（58．8±50．7）mg／L、（518±574）IU／mL,均高于对照组,差异有统计学意义（P〈0．01）;TGF—β1、CTGF、CRP之间均呈正相关关系。TGF—β1和CTGF对RA—ILD诊断的灵敏度、特异度分别为（80．0％,66．7％）、（57．8％,86．7％）。结论TGF—β1和CTGF参与RA-ILD的发生发展过程;TGF—B1和CTGF可作为判断RA—ILD活动期的指标,也可作为早期筛查RA—ILD指标之一。     

三七总苷对酒精性肝损伤大鼠肝脏TGV-β1／Smads、CTGFmRNA表达的影响

目的 研究三七总苷对酒精性肝损伤大鼠肝脏TGF-β1/Smads和CTGF表达的影响。方法 大鼠灌服白酒-玉米油-吡唑混合液14周,建立酒精性肝损伤模型。成模大鼠随机分成模型组、三七总苷组（高、低剂量组）、水飞蓟素组,同时另设正常对照组,均治疗4周后,测定肝功能、大鼠肝组织TGF-β1、Smad3、Smad7、CTGFmRNA的表达量。结果 与模型组比较,三七总苷组能明显降低血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）以及总胆红素（TB）水平,减少肝组织TGF-β1、Smad3、Smad7、CTGF mRNA的表达量;不同剂量组之间,差异有统计学意义（P〈0.05）;高剂量三七总苷组与水飞蓟素组之间,差异无统计学意义（P〉0.05）。结论 三七总苷与对酒精性肝损伤大鼠肝脏TGF-β1/Smads、CTGF表达有抑制作用。     

Agents in development for the treatment of diabetic nephropathy

Diabetic nephropathy is a leading cause of end-stage renal disease, and accounts for significant morbidity and mortality in patients with diabetes. Diabetic nephropathy seems to occur as a result of an interaction between metabolic and haemodynamic factors, which activate common pathways that lead to renal damage. In the past, the treatment of diabetic nephro-pathy has focused on the control of hyperglycaemia. Newer targets, some of which are linked to glucose-dependent pathways, appear to be a major focus of new treatments directed against the development and progression of renal damage as a result of diabetes. It is anticipated that additional thera-peutic approaches that inhibit both metabolic and haemodynamic pathways will include strategies that target growth factors, cytokines and intracellular second messengers. Such an approach is expected to lead to improved therapies for the treatment of diabetic nephropathy.     

金芪降糖片对糖尿病大鼠肾脏保护作用的实验研究

[目的]观察金芪降糖片对糖尿病大鼠肾组织晚期糖化终末产物受体(RAGE)、转化生长因子-β1(TGF-β1)、血管内皮生长因子(VEGF)、结缔组织生长因子(CTGF)表达的影响。[方法]测定造模后20周糖尿病组(DM组)、糖尿病给药组(DD组)和对照组(N组)大鼠24 h尿微量白蛋白定量(UMA)、平均血糖(APG)、甘油三酯(TG)、总胆固醇(TC)、内生肌酐清除率(Ccr)、RAGE、TGF-β1、VEGF、CTGF水平及肾脏形态学改变,评价金芪降糖片的肾保护作用。[结果]与DM组相比,DD组平均血糖、TC差异无统计学意义,Ccr高于DM组,而UMA、TG、RAGE、TGF-β1、VEGF、CTGF水平降低,差异有统计学意义;光镜和电镜下,DD组肾组织损伤程度均轻于DM组。[结论]金芪降糖片可以减轻糖尿病慢性肾损伤的程度,其肾保护作用可能与其降脂及降低RAGE、TGF-β1、VEGF、CTGF水平有关。     

参地补肾胶囊对肾小球硬化大鼠BMP-7、CTGF表达的影响

目的:探讨参地补肾胶囊对肾小球硬化大鼠BMP-7、CTGF表达的影响。方法:采用单侧肾脏切除同时尾静脉注射阿霉素的方法建立肾小球硬化大鼠模型,实验分为正常对照组、模型组、西药(洛汀新)对照组、中药(苏黄泄浊丸)组和参地补肾胶囊组,分组给药处理8周。检测各组大鼠24小时尿蛋白定量、血肌酐(SCr)、尿素氮(BUN)、血浆蛋白(ALB);光镜观察大鼠肾脏病理学变化;免疫组化法检测BMP-7、CTGF表达。结果:各治疗组大鼠24小时尿蛋白及血SCr、BUN、ALB较模型组明显改善(P0.05)。各给药组大鼠肾脏病理变化明显改善。各治疗组均能抑制CTGF的表达(P0.05),上调BMP-7表达(P0.05);参地补肾胶囊组作用明显优于两阳性对照组(P0.05)。结论:参地补肾胶囊对肾小球硬化大鼠肾功能具有保护作用,上调BMP-7表达、抑制CTGF表达可能是其部分作用机制。     

PFD对二甲基亚硝胺诱导的大鼠肝纤维化治疗疗效和CTGF表达的影响

目的观察不同剂量PFD对二甲基亚硝胺（Dimethylnitrosamine DMN）诱导大鼠肝纤维化的治疗作用和CTGF表达的影响,初步探讨其可能的作用机制。方法健康雄性Wistar大鼠105只随机分为正常组21只,给予生理盐水10 mg/kg体重腹腔内注射,每周前三天连续给药,1次/日,连续注射3周;造模组84只,给予1%DMN溶液10 mg/kg体重腹腔注射,每周前三天连续给药,1次/日,连续注射3周。两周末将造模组随机分为4组,每组21只,分别是：模型组、IFN-α治疗组、PFD 120 mg、PFD 240 mg治疗组。各组大鼠均于造模第3周第一天给予药物治疗,每周七天,1次/日,治疗共4周。各组给药剂量及方法如下：正常组、模型组予以0.5%CMCNa 6 m L/kg灌胃;PFD不同剂量组予以相应剂量PFD灌胃;IFN-α组予以IFN-α10万单位/只,皮下注射。治疗四周后处死所有大鼠,留取肝组织行Masson染色,免疫组织化学法测Ⅰ型胶原,CTGF表达。结果 （1）Masson染色SSS半定量评分,模型组与正常组比较显著升高（P〈0.05）。IFN-α组、PFD组SSS半定量评分较模型组显著降低（P〈0.05）。免疫组化法检测肝组织Ⅰ型胶原的表达,模型组与正常组比较显著升高（P〈0.05）,PFD组与模型组比较显著降低（P〈0.05）,IFN-α组与模型组比较无统计学差异（P〉0.05）,（2）免疫组化法检测肝组织CTGF的表达,模型组与正常组比较显著升高（P〈0.05）。PFD 120 mg、PFD 240 mg各组与模型组比较显著降低（P〈0.05）。结论 （1）PFD具有治疗DMN诱导的大鼠肝纤维化的作用,与α-IFN无明显差别。（2）PFD抗DMN诱导大鼠肝纤维化的作用机制可能与下调CTGF的表达,抑制促纤维化因子有关。     

Osteoprotegerin induces morphological and functional alterations in mouse pancreatic islets

Although serum osteoprotegerin (OPG) is significantly increased in diabetic subjects, its potential role in beta cell dysfunction has not been investigated. This study aimed to assess the effect of full-length OPG administered in vivo in mice on pancreatic islet structure and function and its interaction with the renin–angiotensin system (RAS).     

Curcumin diminishes the impacts of hyperglycemia on the activation of hepatic stellate cells by suppressing membrane translocation and gene expression of glucose transporter-2

Diabetes is featured by elevated levels of blood glucose, i.e. hyperglycemia, which might be a risk factor for hepatic fibrogenesis in patients with non-alcoholic steatohepatitis. Hepatic stellate cells (HSCs) are the major effectors during hepatic fibrogenesis. This study was designed to evaluate impacts of high levels of glucose on HSC activation, assess roles of the phytochemical curcumin in attenuating the glucose impacts, and elucidate underlying mechanisms. In this report, levels of intracellular glucose were measured. Contents and gene expression of glucose transporter-2 (GLUT2) in cell fractions were examined. Levels of cellular glutathione and oxidative stress were analyzed. We observed that high levels of glucose induced cell proliferation, type I collagen production and expression of genes relevant to HSC activation, and elevated intracellular glucose levels in cultured HSCs. Curcumin eliminated the stimulatory impacts. Curcumin abrogated the membrane translocation of GLUT2 by interrupting the p38 MAPK signaling pathway. In addition, curcumin suppressed glut2 expression by stimulating the activity of peroxisome proliferator-activated receptor-gamma (PPARγ) and de novo synthesis of glutathione. In conclusion, hyperglycemia stimulated HSC activation in vitro by increasing intracellular glucose, which was eliminated by curcumin by blocking the membrane translocation of GLUT2 and suppressing glut2 expression. The latter was mediated by activating PPARγ and attenuating oxidative stress. Our results presented evidence to impacts of hyperglycemia on stimulating HSC activation and hepatic fibrogenesis, and provided novel insights into the mechanisms by which curcumin eliminated the hyperglycemia-caused HSC activation and potential therapeutic strategies for treatment of diabetes-associated hepatic fibrogenesis.     

In situ expression of connective tissue growth factor in human crescentic glomerulonephritis

Connective tissue growth factor (CTGF) has recently been recognized as an important profibrotic factor and is up-regulated in various renal diseases with fibrosis. The present study describes the sequential localization of CTGF mRNA and its association with transforming growth factor (TGF)-1 in human crescentic glomerulonephritis (CRGN). Furthermore, we examined the phenotype of CTGF-expressing cells using serial section analysis. Kidney biopsy specimens from 18 CRGN patients were examined using in situ hybridization and immunohistochemistry. CTGF mRNA was expressed in the podocytes and parietal epithelial cells (PECs) in unaffected glomeruli. In addition, it was strongly expressed in the cellular and fibrocellular crescents, particularly in pseudotubule structures. Serial sections revealed that the majority of CTGF mRNA-positive cells in the crescents co-expressed the epithelial marker cytokeratin, but not a marker for macrophages. Moreover, TGF-1, its receptor TGF- receptor-I, and extracellular matrix molecules (collagen type I and fibronectin) were co-localized with CTGF mRNA-positive crescents. Our results suggest that CTGF is involved in extracellular matrix production in PECs and that it is one of the mediators promoting the scarring process in glomerular crescents.