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1.
黄姗  曹文富 《医学争鸣》2009,(14):F0003-F0003
0引言 糖尿病肾病(diabeticn ephropathy,DN)的病理改变是肾小球硬化,肾小管间质纤维化。TGF-β1与Ⅳ型胶原是重要的促纤维化因子^[1],解聚复肾宁(Jiejufushenning,JJFSN)对DN有明显疗效。我们研究JJFSN对糖尿病(diabetes mellitus,DM)大鼠肾功能、肾脏TGF-β1 mRNA,Ⅳ型胶原蛋白表达的影响及肾保护作用。  相似文献   

2.
张璟  周飞舟  邹贵勉 《重庆医学》2007,36(5):411-413,416
目的 探讨肾脏组织中血小板反应蛋白1(thrombospondin-1,TSP-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)在肾间质纤维化发生、发展中的表达及意义.方法 选择不同类型肾脏疾病患者53例,按肾间质病理损伤程度对肾组织标本进行分组:正常对照组5例、轻度损伤组18例、中度损伤组19例、重度损伤组11例.用免疫组织化学技术和计算机真彩色图像分析系统半定量检测肾间质的TSP-1、VEGF、CD34、TGF-β1、α-SMA和Ⅳ型胶原表达情况.结果 在正常对照组,TSP-1无阳性表达;TGF-β1在肾小管上皮细胞浆偶见表达;α-SMA仅在血管壁表达;肾间质Ⅳ型胶原在肾小管基底膜、动脉管壁呈线状表达.而VEGF在肾小管上皮细胞及足突细胞浆均可见表达,CD34在肾小管周围毛细血管内皮细胞表达.随着病变程度加重, TSP-1、TGF-β1、α-SMA和Ⅳ型胶原其表达量及面积显著增加(P<0.01),与肾间质病理损害程度呈显著正相关(r=0.86,0.674,0.779,0.784).而VEGF及CD34表达量及面积则显著递减(P<0.01),与肾间质病理损害程度呈显著负相关(r=-0.715,-0.672).结论 随着肾间质病理损伤程度加重,TSP-1在肾小管上皮细胞、肾间质区表达增强,与肾间质损害程度呈显著正相关;VEGF在肾小管上皮细胞、足细胞表达减弱,与肾间质损害程度呈显著负相关.提示TSP-1与VEGF对肾小管周围毛细血管作用失衡,使肾小管周围毛细胞血管减少,加重肾组织缺氧,导致慢性肾间质纤维化发生、发展.  相似文献   

3.
目的:探讨疏血通注射液对实验性糖尿病大鼠尿蛋白和转化生长因子β_1(Transforming growthfactor β_1,TGF-β_1)、Ⅳ型胶原(Cofiegen type Ⅳ,Col-Ⅳ)表达的影响.方法:采用链脲佐菌素(Streptozotocin,STZ)制备早期糖尿病肾病(Diabetic nephropathy,DN)模型,随机分为正常对照组、DN未治疗组、疏血通治疗组、苯那普利对照组,8周后观察尿白蛋白排泄率(Urinary albumin excretion rate,UAER)、尿β_2微球蛋白(β_2-miro globulin,β_2-MA)、肾脏肥大指数(KW/BW)的变化;免疫组化法检测肾组织TGF-β_1、Col-Ⅳ的表达水平.结果:与DN未治疗组相比,疏血通组的UAER、尿β_2-MA、KW/BW均下降(P<0.05或P<O.01),肾组织TGF-β_1、Col-Ⅳ表达下调(P<0.05).结论:疏血通注射液对糖尿病大鼠具有肾脏保护作用,其机制可能与下调肾组织TGF-β1、Col-Ⅳ的表达有关.  相似文献   

4.
潘春勤  周学才  杜鹏举  刘杰 《西部医学》2021,33(10):1423-1427+1435
【摘要】 目的 探讨TGF-β/Smad/RUNX3信号通路在糖尿病肾病(DN)大鼠肾小管上皮细胞 间充质转化(EMT)过程中的作用。 方法 将45只Wistar雄性大鼠随机分成三组:对照组、模型组和实验组,每组各15只,实验组和模型组制备DN大鼠模型。按照实验分组进行给药。末次给药后,用血糖仪检测各组大鼠血糖含量,全自动生化分析仪检测各组大鼠24 h尿蛋白、血尿素氮及血肌酐含量,过碘酸希夫(PAS)、天狼星红(SR)染色观察各组大鼠肾脏组织病理变化,酶联免疫吸附测定(ELISA)检测各组大鼠血清白介素1β(IL-1β)、白介素6(IL-6)表达水平,蛋白免疫印迹(Western blot)检测各组大鼠肾脏组织α-SMA、E-cadherin、TGF-β1、Smad3、Smad4、RUNX3蛋白表达情况。 结果 与对照组相比,模型组大鼠肾小管肥大增生,肾间质有炎症细胞浸润现象,肾间质胶原纤维沉积、24 h尿量、24 h尿蛋白、血糖、血尿素氮、血肌酐浓度、血清IL-1β、IL-6表达量、肾脏α-SMA、TGF-β1、Smad3、Smad4蛋白表达显著升高 (P<0.05),肾脏E-cadherin、RUNX3蛋白表达显著降低 (P<0.05);与模型组相比,实验组大鼠肾小管肥大减轻,炎症细胞减少,肾间质胶原纤维沉积、24 h尿量、24 h尿蛋白、血尿素氮、血肌酐浓度、血清IL-1β、IL-6、肾脏α-SMA、TGF-β1、Smad3、Smad4蛋白表达显著降低 (P<0.05),肾脏E-cadherin、RUNX3蛋白表达显著升高 (P<0.05)。 结论 β抑制剂可通过抑制TGF-β/Smad通路激活促进RUNX3表达,减少糖尿病肾病大鼠肾间质纤维化及促炎因子分泌,抑制肾小管上皮细胞EMT的发展。  相似文献   

5.
目的探讨芪卫颗粒对自发性2型糖尿病KK-Ay小鼠肾组织USF2表达的影响及对DN肾纤维化的干预机制。方法将SPF级12周龄雄性KK-Ay小鼠60只造模后随机分为模型组、芪卫颗粒组、缬沙坦组,20只C57BL/6J小鼠为正常对照组。24周龄时,检测各组血糖、糖化血红蛋白、肾功能(BUN、SCr)、尿蛋白;用光镜和电镜观察肾组织的结构变化,Masson染色观察肾脏纤维化程度;RT-PCR检测肾组织中USF2、TGF-β_1的mRNA表达,Westernblot检测USF2蛋白表达,免疫组化染色观察TGF-β_1、Col-Ⅳ、FN在肾脏中的表达及分布情况。并用图像定量分析系统进行统计分析。结果 (1)与正常对照组比较,模型组肾组织中USF2和TGF-β_1的mRNA表达明显升高,免疫组化显示模型组TGF-β_1、ColⅣ、FN在肾小球和肾小管表达均明显增加,纤维化程度明显加重,肾功能减退(P<0.05)。(2)与模型组比较,芪卫颗粒组和缬沙坦组肾功能和尿蛋白得到改善,肾脏纤维化减轻,USF2和TGF-β_1基因及纤维化蛋白水平表达均显著降低(P<0.05)。(3)相关分析表明,USF2与TGF-β_1呈正相关(r=0.82,P<0.05)。结论 (1)USF2正向调节TGF-β_1表达,刺激TGF-β_1所调节的下游纤维化蛋白ColⅣ、FN表达增加,导致细胞外基质积聚。(2)芪卫颗粒下调KK-Ay小鼠肾组织USF2基因和蛋白表达,负向调节TGF-β_2表达,可能是其治疗DN肾纤维化的机制之一。  相似文献   

6.
目的:探究姜黄素通过TGF-β/Smads信号通路对肾缺血再灌注后肾小管间质纤维化的抑制作用.方法:将40只健康SD大鼠按随机数字表法平均分为假手术组、模型组、低剂量组和高剂量组.使用夹闭法松开肾蒂的方法复制肾缺血再灌注大鼠模型.检测血清中血清肌酐(serum creatinine,Scr)和尿素氮(urea nitrogen,BUN)水平、肾组织胶原含量、肾组织的病理变化以及肾脏中转化生长因子-β1 (transforming growth factor β1,TGF-β1)、Smad3和Smad7蛋白表达水平.结果:假手术组肾小管形态正常,模型组肾小管间质呈现明显的病理变化,低剂量组和高剂量组肾小管间质纤维病理变化明显改善,且高剂量组改善程度高于低剂量组;模型组的肾小管间质纤维化评分、Scr、BUN、胶原含量、TGF-β1和Smad3明显高于假手术组,Smad7明显低于假手术组(P<0.05);低剂量组和高剂量组肾小管间质纤维化评分、Scr、BUN、胶原含量、TGF-β1和Smad3均明显低于模型组,Smad7明显高于模型组(P<0.05);高剂量组肾小管间质纤维化评分、Scr、BUN、胶原含量、TGF-β1和Smad3评分明显低于低剂量组,Smad7明显高于低剂量组(P<0.05).结论:姜黄素对肾缺血再灌注后肾小管间质纤维化具有抑制作用,其作用机制可能为抑制TGF-β/Smad信号转导通路.  相似文献   

7.
陈超  ;武德梅  ;孙建洁 《医学综述》2014,(11):1961-1962
肾脏纤维化的特点是细胞外基质(ECM)成分的积累、肾小球硬化和肾小管间质纤维化的形成。转化生长因子β(TGF-β)是重要的致纤维化因子,它参与肾脏纤维化的各个环节。TGF-β诱导足细胞凋亡、肾小球系膜细胞肥大、增殖并最终凋亡,以及ECM的合成,还可诱导内皮细胞间质转化为肾小球肌成纤维细胞,引起肾小球硬化。TGF-β促进肾小管上皮间质转化,ECM生产和凋亡,导致肾小管间质纤维化。  相似文献   

8.
目的:探讨热休克蛋白47( heat shock protein 47,HSP47)在2型糖尿病肾病(diabetic nephropathy,DN)中的表达及其意义.方法:45例2型DN患者分为DN组25例和轻微病变性肾病(MCD)组20例.使用常规病理组织学方法观察肾小球、肾小管间质和血管的病变程度,免疫组织化学染色法观察各实验组肾组织内HSP47、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)及Ⅳ型胶原(Col Ⅳ)的表达,并进行免疫双染共定位分析.结果:与MCD组比较,DN组肾小球内HSP47、α-SMA、Vimentin及Col Ⅳ表达明显增加(P<0.05);肾小管间质纤维化区域内HSP47、α-SMA及Col Ⅳ表达亦明显增加(P<0.05),Vimentin则在肾小管间质内表达显著性增加(P<0.01).免疫双染结果显示,DN组在增生硬化的肾小球系膜区及肾小管间质纤维化处,HSP47表达阳性细胞内同时有α-SMA阳性表达,并且HSP47表达阳性细胞同时具有Vimentin阳性表达.结论:HSP47过度表达或许通过帮助前胶原分子细胞内处理及加工,参与2型DN肾小球硬化及肾小管间质纤维化的形成.  相似文献   

9.
目的:探讨转化生长因子β1(TGF-β1)在人系膜增生性肾小球肾炎(MsPGN)患者肾组织中对Ⅰ、Ⅲ、Ⅳ型胶原的影响及在肾纤维化中的作用.方法:采用免疫组织化学技术、天狼猩红染色偏振光法及计算机图像分析系统,观测31例MsPGN患者肾组织中TGF-β1的表达和Ⅰ、Ⅲ、Ⅳ型胶原的分布,分析它们之间的相互关系.结果:MsPGN患者随着肾纤维化的加重,在肾小球增生扩张系膜中Ⅳ型胶原明显增加,并出现了Ⅰ、Ⅲ型胶原;在肾间质中TGF-β1和Ⅰ、Ⅲ、Ⅳ型胶原的表达明显增加,且以Ⅲ、Ⅳ型胶原的增加为主.TGF-β1与肾间质中Ⅰ、Ⅲ、Ⅳ型胶原呈正相关(r=0.82、0.92,P<0.01),与Ⅰ/Ⅲ、Ⅰ/Ⅳ、Ⅲ/Ⅳ呈负相关(r=-0.83、0.92,P<0.001).结论:在MsPGN中TGFβ1的过度表达和Ⅰ、Ⅲ、Ⅳ型胶原的增加与肾小球和肾小管纤维异常分布关系密切,可能是其导致肾小球硬化和肾间质纤维化的主要机理之一.  相似文献   

10.
目的观察单侧输尿管梗阻(UUO)大鼠中骨形态发生蛋白-7(BMP-7)在肾小管间质中的表达部位、动态变化及其与肾小管间质损害的关系.方法60只Wistar大鼠随机分为正常大鼠组、假手术组和单侧输尿管梗阻组,分别于术后1、3、7、14 d处死,采用RT-PCR方法检测BMP-7 mRNA、TGF-β1mRNA表达水平,免疫组织化学方法检测肾小管间质中BMP-7、TGF-β1的蛋白定位、表达及其与输尿管梗阻后肾小管间质损害的关系.结果与对照组相比,BMP-7 mRNA于术后第1天即出现表达下降并随梗阻时间延长递减,而TGF-β1mRNA随梗阻时间延长递增.BMP-7蛋白在对照组中高度表达,主要分布在肾小管及肾间质,肾小球内基本无表达.在梗阻组随着肾间质损害的加重,BMP-7蛋白表达呈进行性下降,而TGF-β1蛋白表达则逐渐增加.BMP-7与TGF-β1蛋白及mRNA表达均成显著负相关(r=-0.875;r=-0.843,n=20,P<0.05).结论BMP-7于肾小管间质病变早期即出现表达下调,早于肾间质纤维化的出现,其表达量与肾间质TGF-β1表达负相关且随间质病变进展进行性下降.BMP-7表达下调可能参与介导肾小管间质损害的发生发展.  相似文献   

11.
Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P < 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (>0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P <0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P < 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.  相似文献   

12.
Objective: To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods: SD rats served as both donors and recipients. 4℃ sodium lactate Ringer's was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava (IVC) inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results: Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion: This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.  相似文献   

13.
Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P< 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P< 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.  相似文献   

14.
目的:评价使用安心颗粒对急诊经皮冠状动脉介入术(PPCI)术后生活质量的影响.方法:将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组(术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次)和对照组(仅接受基础药物治疗).所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表(MIDAS)、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果:入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异(P>0.05);出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低(P<0.05);组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低(P<0.05).两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血(P>0.05).两组发生轻度血小板减少症的患者数比较无差异(P>0.05).结论:PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.  相似文献   

15.
Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P<0.01);the MAP decreased(P<0.01)and the HR increased drastically(P<0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.  相似文献   

16.
Objective:To investigate the gene expression of osteoprotegerin(OPG) and osteoclast differentiation factor(ODF) in the bone tissue of patients with hip fracture due to osteoporosis. Methods:OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers(over 50 years old) with hip fracture(Observer Group) and 30 cases of hip facture sufferers with no osteoporosis(Control group) were analyzed with the Semi-Quantitative RT-PCR method. Results:The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion:Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.  相似文献   

17.
Objective:To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas(SPTP). Methods:Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin(HE) staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results:Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin(9/9 cases), AAT(9/9 cases), NSE(9/9 cases), ACT(7/9 cases), CK20(2/9 cases), CgA(1/9 cases), S-100(3/gcases), PR(4/gcases), Syn(3/9 cases) and CD56(5/9cases), negative in CEA and ER. Conclusion:SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.  相似文献   

18.
Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.  相似文献   

19.
Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.  相似文献   

20.
Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.  相似文献   

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