γ射线辐射对大鼠胸主动脉平滑肌细胞肾上腺髓质素和内皮素生成的影响

为观察^60COγ射线辐射对培养的大鼠血管平滑肌细胞（VSMC）肾上腺髓质素（Adm)内皮素（ET）生成的影响，以探讨辐射防治再狭窄的机制，采用逆转录－竞争性聚合酶链反应观察经0,1,,24,25Gy辐射的培养大鼠血管平滑肌细胞Adm和ET mRNA水平；用放免方法测定相应的Adm和ET的生成。发现1Gy辐射对VSMC Adm和ET的生成及基因表达均无显著影响。14Gy辐射后VSMC生成的Adm较对照组增加270％（P＜0．05），ET的生成较对照组降低27．3％（P＜0．01）；25Gy辐射使VSMC生成的Adm和ET含量分别增加233％（P＜0．05）和降低58．0％（P＜0．01）。14和25Gy辐射分别使细胞Adm mRNA水平较对照组增加82．4％（P＜0．01）和101％（P＜0．01），使ET mRNA水平较对照组降低47．1％（P＜0．01）及40．2％（P＜0．01）。表明^60Coγ射线辐射可以促进Adm的蛋白及基因表达，而抑制ET的蛋白及基因表达，增加了Adm/ET比值。     

冠脉搭桥患者血浆肾上腺髓质素和内皮素-1的变化

肾上腺髓质素(adrenomedullin,AM)是具有多种生物学效应,参与许多心血管系统疾病的病理过程,与疾病的严重程度相关[1-2].内皮素-1(endothelin-1,ET-1)与AM共同调节基础状态下的血管紧张度,引起血管的自主收缩及扩张.有关影响AM和ET-1分泌的因素很多,但心外科冠脉搭桥术对其影响尚未见报道,我们探讨体外和非体外循环两种冠脉搭桥方式对血浆AM及ET-1的影响.     

肾上腺髓质素在正常大鼠大脑的分布

目的观察正常大鼠脑组织肾上腺髓质素(ADM)及ADM mRNA的表达及分布。方法免疫组织化学法(SABC法)检测ADM阳性细胞表达、原位杂交法检测ADM mRNA阳性细胞表达,RT-PCR法检测ADM mRNA在正常大鼠脑内的表达。结果在正常大鼠大脑内有ADM及ADM mRNA的表达,主要表达在大脑皮质锥体细胞、海马CA1区、CA2区、CA3区、CA4区锥体细胞、齿状回颗粒细胞层、丘脑的室旁核、视上核、丘脑内侧核、丘脑外侧核、缰内侧核、室旁组织、脉络丛、室管膜细胞、尾状核、壳核、苍白球、血管内皮细胞及平滑肌细胞,其中室旁组织为高表达区。结论ADM在中枢神经系统的广泛分布,预示着ADM在中枢神经系统内具有重要的作用。     

高血压患者肾上腺髓质素、内皮素测定及其临床意义

肾上腺髓质素 (ＡＤＭ)、内皮素 (ＥＴ)是体内两个作用相反舒缩血管作用的生物活性物质。有研究表明 ,ＡＤＭ与ＥＴ相互作用 ,参与内皮源细胞旁分泌、自分泌调节体系的构成 ,共同协调血管张力 ,在原发性高血压的动态发生发展过程中起重要作用[1] 。因此本文选择ＡＤＭ、ＥＴ这两个机能上具有相互拮抗作用的血管活性肽作为研究对象 ,分析两者在高血压中的作用。对象和方法一、对象 :选择 2 0 0 2年 4月～ 2 0 0 2年 11月我院内科门诊确诊为高血压患者 4 3例 (男 2 4 ,女 19)。年龄 3 2～ 64岁 ,平均 4 7± 13岁。诊断及分级依据 1999年ＷＨＯ…     

肾上腺髓质素和内皮素-1在妊娠高血压疾病患者胎盘绒毛组织中表达的研究

目的研究胎盘绒毛组织肾上腺髓质素(ADM)和内皮素-1(ET-1)在妊娠高血压疾病发病中的作用。方法用免疫组化法检测ADM和ET-1在正常晚孕妇女(20例)和妊娠高血压疾病患者(60例)胎盘绒毛膜组织中的表达情况,结果用计算机软件分析处理。结果ADM和ET-1在胎盘绒毛组织合体滋养细胞和毛细血管内皮细胞中均有表达,位于胞浆和胞膜。与正常晚孕期胎盘组织相比,妊高征患者组织中ADM平均灰度值增高,而ET-1平均灰度值降低(113.45±3.24vers 131.55±5.68,135.48±3.21 vers 119.05±5.41,P<0.05);随着妊高征病情加重,ADM增高和ET-1降低的幅度更加显著,轻、重度子痫前期组患者胎盘组织中ADM平均灰度值高于妊娠高血压组,而ET-1平均灰度值低于妊娠高血压组(135.48±4.96,141.52±5.37 vers 117.64±5.36;116.64±6.75,109.27±4.98 vers 131.24±4.39,P<0.05),而轻、重度子痫前期组之间比较无显著性差异(P>0.05)。结论胎盘绒毛组织ADM表达减弱,ET-1表达增强可能在妊娠期高血压疾病发病中起重要作用。     

肾上腺髓质素研究进展

肾上腺髓质素是一种新发现的降压肽，广泛分布于体内多种脏器、神经组织和某些神经细胞瘤中。具有调节动脉血压、呼吸系统、肾脏、细胞增殖和迁移等作用。它在高血压的降压、呼吸系统疾病的发生及治疗方面有重要意义。     

肾上腺髓质素

肾上腺髓质素（ＡＭ）是近年发现的一种在体内广泛分布的内源性血管活性肽。人ＡＭ前体含有１８５个氨基酸残基，成熟ＡＭ由５２个氨基酸残基组成。ＡＭ具有舒张动脉、降低血压、排钠利尿等生物作用，在人、鼠体内分布广泛     

肾上腺髓质素在糖尿病肾病中的变化及作用

目的: 探讨肾上腺髓质素(AM)在糖尿病肾病中的变化及作用。方法: 通过体外人肾小球系膜细胞培养实验,观察高糖条件对系膜细胞AM mRNA、转化生长因子-β₁(TGF-β₁)mRNA表达、分泌及细胞外基质(层粘连蛋白和Ⅳ型胶原)含量的影响及肾上腺髓质素干预对高糖不良作用的影响。结果: 在高糖条件下培养的人肾小球系膜细胞AMmRNA、TGF-β₁mRNA表达和AM、TGF-β₁分泌较低糖对照组分别增加1.01倍、0.59倍和3.49倍、1.61倍;细胞外基质蛋白LN和Ⅳ型胶原含量分别升高0.95倍和1.13倍。用不同浓度AM(10^-7、10^-8和10^-9 mol/L)干预后,TGF-β₁mRNA表达分别下降50%、28%和16.2%,TGF-β₁含量分别下降39%、26%和11%;LN含量分别下降53%、45%和18%,Ⅳ型胶原含量分别下降29%、26%和20%。结论: 葡萄糖水平升高是AM表达分泌的剌激因子之一。AM的肾脏保护作用可能与抑制TGF-β₁的表达与分泌,进而减少基质蛋白和胶原的过度积聚相关。     

肾上腺髓质素对肾脏的生物学效应机制

肾上腺髓质素是近来发现的一种新的生物活性多肽，在调节肾脏功能调节中发挥重要作用。本综述了肾上腺髓质素及其对肾血管、肾血流动力学、肾脏细胞与利尿利钠的影响及其机制。     

肾上腺髓质素与脑血管病

肾上腺髓质素 (Adrenomedullin ,AM )是一种新发现的生物活性肽 ,在人体多种组织中都有AMmRNA的表达。AM具有扩张血管、降低血压、排尿利钠、抑制内皮细胞凋亡、影响内分泌的功能。在脑血管病的发生发展中起重要的保护作用。     

Losartan reduces myocardial interstitial fibrosis in diabetic cardiomyopathy rats by inhibiting JAK/STAT signaling pathway

Purpose: This study was designed to investigate the effect of losartan on the myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM) rats. Methods: In this study, a total of 48 male Wister rats (3 groups of 16 animals each) were examined, including the control group, DCM group and losartan-treated (DCM + L) group. Control group was fed with standard diet (14 KJ/g); DCM group and losartan-treated (DCM + L) group were both fed with high glucose and fat diet (20 KJ/g). Diabetes was induced by streptozotocin (STZ) intraperitoneal injuction (IP, 30 mg/kg body weight). Rats of DCM + L group were treated with losartan (30 mg/kg body weight) daily by oral gavage for 16 weeks. Biochemical, hemodynamic, histological and western blotting analyses were performed. Results: Compared with DCM rats, the quantity of p-JAK2 and p-STAT3 in myocardium of rats treated with losartan was lower, the expression of TGF-β1 was down-regulate, the content of collagen in myocardium decreased, LVSP and ± dp/dt increased, LVEDP decreased, the level of myocardial fibrosis reduced, and heart function improved evidently. Conclusion: Losartan has a protective effect on heart function against myocardial interstitial fibrosis of DCM by inhibiting JAK/STAT signaling pathway and lowering the expression of TGF-β1.     

厄贝沙坦减轻糖尿病肾病大鼠肾损伤

目的观察厄贝沙坦能否减轻糖尿病肾病(DN)大鼠的肾损伤。方法将大鼠随机分为对照组、DN模型组、厄贝沙坦治疗组。于22周测体质量、随机血糖、24 h尿微量白蛋白、血肌酐、尿素氮,观察肾脏形态改变。应用荧光定量PCR检测miR-192 mRNA在大鼠肾组织中的表达;蛋白免疫印迹法、免疫组织化学法检测肾组织TGF-β1、Zeb1、collagenⅠ蛋白的表达。结果与对照组比较,DN组大鼠体质量、随机血糖、血肌酐、尿素氮和24 h尿微量白蛋白显著增高(P<0.05);与DN组比较,厄贝沙坦治疗组大鼠体质量、随机血糖、血肌酐、尿素氮和24 h尿微量白蛋白显著降低(P<0.05)。厄贝沙坦治疗可以改善DN大鼠的一般情况和肾脏病理损害。与对照组相比,DN组miR-192 mRNA在DN大鼠肾脏的表达下调(P<0.05);与DN组相比,厄贝沙坦组miR-192 mRNA表达上调(P<0.05);与对照组大鼠相比,DN组肾组织的TGF-β1、ZEB1和collagenⅠ蛋白表达量明显增加(P<0.05);与DN组相比较,厄贝沙坦治疗可以减少TGF-β1、ZEB1和collagenⅠ蛋白的表达(P<0.05)。结论厄贝沙坦可减轻糖尿病肾病大鼠的肾损伤。     

核因子-κB在糖尿病肾组织中的表达及干预治疗

核因子(NF)-κB是细胞中一种重要的核转录因子，它参与细胞内的信号转导、免疫反应、炎症反应以及细胞生长发育等多种生物过程，在细胞因子诱导的基因表达中起关键性的调控作用。活化的NF-κB可能通过调控许多炎症因子的转录过程在糖尿病肾病（DN）的发生发展过程中起重要作用。抑制NF-κB的激活和IκB的降解等干预治疗可能是防治DN的手段之一。     

Melatonin and/or rowatinex attenuate streptozotocin-induced diabetic renal injury in rats

The study aimed to explore the prophylactic effect of melatonin, rowatinex; a naturally occurring renal drug, and its combination on diabetic nephropathy in type 2 diabetic rats. Diabetes was induced by intraperitoneal injection of a single dose of streptozotocin (50 mg/g body weight). Three days before diabetes induction, rats were daily treated with melatonin, rowatinex and their combination continuously for 8 weeks. Evaluation was done through measuring blood urea nitrogen (BUN), serum uric acid, serum creatinine, urine creatinine, creatinine clearance, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), total antioxidant capacity (TAC), kidney injury molecule-1 (KIM-1), heat shock protein-70 (HSP-70), caspase-3, transforming growth factor β1 (TGFβ1), DNA degradation by the comet assay and total protein contents. Histopathologic study was also done for the kidney and the pancreas. Drastic changes in all measured parameters of the diabetic rats were observed. Treatment with melatonin and rowatinex showed amelioration to variable degrees. In conclusion, melatonin showed the most potent effect on protecting rats from deleterious action of diabetic nephropathy followed by its combination with rowatinex.     

Blockade of oxidative stress by vitamin C ameliorates albuminuria and renal sclerosis in experimental diabetic rats

PURPOSE: Oxidative stress has been suggested to play a role as a common mediator of apoptosis and kidney damage in diabetes. However, it is uncertain whether the apoptosis occurs in the kidney during the course of diabetes. We investigated the occurrence of apoptosis in the diabetic rat kidney, the role of oxidative stress and the effect of an antioxidant on apoptosis in the diabetic rat kidney. MATERIALS AND METHODS: Otsuka-Long-Evans-Tokushima-Fatty rats, an animal model for type 2 diabetes, were randomized into a non-treated diabetic (n=8) and a vitamin C-treated group (n=8). Long-Evans Tokushima Otsuka rats (n=8) were used as a control. RESULTS: Apoptosis was present in the epithelial cells of the proximal tubules in diabetic rats. The number of apoptotic cells, albuminuria, proteinuria, glomerular and tubulointerstitial sclerosis, and renal malondialdehyde were significantly decreased in vitamin C-treated diabetic rats when compared to the untreated diabetic rats. The decreased slit pore density (number of slit pores per underlying glomerular basement membrane length) as assessed by electron microscopy was also significantly restored by treatment with vitamin C without significantly affecting plasma glucose in diabetic rats. CONCLUSION: By blocking these pathophysiologic processes, a blockade of oxidative stress by vitamin C might become a useful adjunct to albuminuria and renal sclerosis in diabetic nephropathy.     

霉酚酸酯对糖尿病大鼠肾脏的保护作用

目的探讨霉酚酸酯(MMF)对糖尿病模型大鼠肾脏的保护作用及其机制。方法SD大鼠随机分为3组:对照组、糖尿病模型组和糖尿病治疗组。治疗12周后,检测大鼠血糖(BG)、血尿素氮(BUN)、血肌酐(Scr)、肾肥大指数(肾重KW/体重BW)、肌酐清除率(Ccr)和24h尿蛋白(24Upro)。肾组织做常规光镜和电镜检查。用免疫组织化学方法检测肾组织中细胞间黏附分子-1(ICAM-1)和增殖细胞核抗原(PCNA)蛋白的表达,半定量RT-PCR的方法检测肾组织中ICAM-1mRNA的表达。结果与对照组相比,糖尿病组大鼠BG、KW/BW、24Upro、BUN、Scr和Ccr均显著升高(P<0.05或0.01);系膜密度和肾小球基底膜厚度均显著增加(P<0.01);肾组织内ICAM-1和PCNA的蛋白质表达及ICAM-1的mRNA表达均显著上调(P<0.05或0.01)。除血糖外,治疗组上述指标均显著回降(P<0.05或0.01)。结论MMF对糖尿病肾病有保护作用,其机制可能与下调ICAM-1和PCNA的表达有关。     

吡格列酮对2型糖尿病大鼠肾脏及单核细胞 趋化蛋白 1表达的影响

目的：观察吡格列酮对2型糖尿病(Type 2 diabetes mellitus,T2DM)大鼠血、尿单核细胞趋化蛋白 1（monocyte chemoattractant protein 1,MCP 1）表达及肾脏组织结构和功能的影响。方法：正常对照组(NC组)喂以常规饲料;采用高糖高脂膳食、小剂量链脲佐菌素（streptozotocin,STZ）注射的方法建立2型糖尿病大鼠模型,将成模的大鼠随机分为糖尿病（DM组）和吡格列酮（PIO组）,后用吡格列酮对PIO组大鼠进行干预治疗。8周后检测血糖水平、尿生化结果、肾脏组织病理的改变情况,同时检测尿MCP 1指标的变化。结果：与NC组比较,DM组和PIO组第8周空腹血糖及糖化血红蛋白水平均明显升高,但DM组、PIO组间差异无统计学意义（P＜0.05）;第8周DM组、PIO组尿白蛋白/尿肌酐(urinary albumin／creatinine ratio,ACR)、尿视黄醇结合蛋白(urinary retinol binding protein,URBP)、尿MCP 1(urinary monocyte chemoattractant protein 1,UMCP 1)和肾脏肥大指数均高于NC组,PIO组4项指标较DM组明显降低,且UMCP 1与ACR,URBP及肾脏肥大指数呈正相关;病理显示PIO组大鼠肾小球病变程度均较DM组明显减轻,MCP 1表达减少。结论：吡格列酮对2型糖尿病大鼠肾脏有明显的保护作用,这种保护作用是独立于降糖作用之外的。其机制可能与其抑制肾组织MCP 1表达及其排泄有关。     

WNT4及其抑制因子SFRP1在糖尿病肾病大鼠肾组织中的表达

目的观察WNT4/β-catenin信号通路及其抑制因子分泌型卷曲相关蛋白1(SFRP1)在糖尿病肾病(DN)大鼠肾组织中的表达变化,探讨其在肾脏纤维化发生发展中的可能作用。方法将大鼠随机分为正常对照(NC)组和DN组,8只/组。尾静脉注射STZ 55 mg/kg复制IDDM模型。HE、PAS及Masson染色观察肾组织形态学结构和纤维化病变;免疫组织化学法观察WNT4和β-catenin蛋白在肾组织的表达部位;Western blot检测WNT4、SFRP1、β-catenin、p-GSK-3β、GSK-3β、CollagenⅠ、α-SMA和E-cadherin蛋白在肾组织中的表达;Real-time PCR检测WNT4及SFRP1 mRNA在肾组织中的表达。结果与NC组相比,DN组大鼠肾组织纤维化病变明显;WNT4蛋白和mRNA表达显著增多(P<0.05);β-catenin、p-GSK-3β、α-SMA和CollagenⅠ蛋白的表达显著增多(P<0.05);E-cadherin蛋白表达显著减少(P<0.05);SFRP1蛋白和mRNA表达显著下降(P<0.05)。结论在DN发病中,WNT4/β-catenin信号通路异常活化;SFRP1表达减少可能抑制该通路,促进了DN肾纤维化的发生发展。     

Changes of urinary angiotensinogen concentration and its association with urinary proteins in diabetic rats

Objective: It had been reported that angiotensinogen might be a marker for activation of renin-angiotensin system, which was associated with the development of diabetic nephropathy. The purpose of this study was to investigate the functional roles of AGT in DN in vitro. Methods: Diabetic rat models were built by single intraperitoneal injection of streptozotocin. The diabetic rats were divided into three groups, two of the three groups were treated with different doses of losartan, the other diabetic group was as control and normal rats acted as healthy control. In a 12-week investigation, we detected the changes of AGT in all rats’ blood and urine and the association between AGT concentration and RAS activation and urinary proteins were analyzed in this study. Results: The serum AGT of rats had no significant differences (P>0.05 for all). The urinary AGT of the diabetic rats was significantly different from the control group, moreover, the urinary AGT of the diabetic rats under different treatments was also obviously different (P<0.05 for all). Besides, the results of immunohistochemical assay indicated that AGT expression level was correlated with renal tissues damage. The level of AGT was positively associated with urinary protein (r=0.493, P<0.01) and negatively correlated with CCr (r=-0.474, P=0.007) and the dose of ARB (r=-0.575, P=0.001). Moreover, the dose of ARB was independently associated with urinary AGT (B=-2.963, P=0.024) in diabetic rats. Conclusion: Urinary AGT may be a marker for the activation of local RAS in kidney and independently associated with ARB.     

丹参联合黄芪对糖尿病肾病大鼠肾脏线粒体呼吸及能量代谢的影响

目的:探讨丹参联合黄芪对糖尿病肾病(DN)大鼠肾脏功能及线粒体呼吸和能量代谢的影响。方法:选择健康SD大鼠,使用链脲佐菌素制作DN大鼠模型,按随机数字表法分为DN模型组(DN组)、丹参注射液干预组(丹参组)、黄芪注射液干预组(黄芪组)、丹参联合黄芪注射液干预组(联合组)和正常对照组(对照组),每组各8只。丹参组加予丹参注射液灌胃,黄芪组加予黄芪注射液灌胃,联合组加予丹参联合注射液灌胃,正常组和DN组同时给予等量的生理盐水,连续喂养6周。检测空腹血糖、血尿素氮、血清肌酐、24小时尿量及尿蛋白定量,留取肾组织,高效液相色谱法检测ATP、ADP、AMP,提取线粒体,氧电极法检测线粒体3态呼吸速率(T3)、4态呼吸速率(T4)和呼吸控制率(RCR)。结果:与DN组大鼠比较,丹参组、黄芪组和联合组大鼠的血糖水平、血尿素氮、血清肌酐、尿蛋白定量下降,24 h尿量增加,肾脏组织线粒体T3和RCR升高,ATP、ADP含量增加,P均<0.05。但联合组与丹参组和黄芪组对比,各项指标无显著差异。结论:丹参和黄芪单用及联合可能通过改善DN大鼠肾脏线粒体呼吸功能及能量代谢,改善DN大鼠肾脏的功能。丹参联合黄芪组较单纯丹参或单纯黄芪无显著优势。