阿魏酸钠在糖尿病肾病中的应用

1．对象与分组：我院2008年1月至12月收治67例糖尿病肾病（DN）住院患者，其中男41例，女26例，年龄27-73岁，病程3．7～26年，诊断标准均符合1998年WHO糖尿病诊断及按Mogensen的DN分期法，排除近4周内发生血栓栓塞性病例及肌酐清除率（Ccr）〈30％者。     

阿魏酸钠治疗早期糖尿病肾病的初步临床研究

阿魏酸是桂皮酸的衍生物之一,当归、川芎、木贼、升麻等多种中药中都含有阿魏酸。阿魏酸的钠盐现研究表明是一种新的非肽类内皮素受体拮抗剂[1],而内皮素（ET）通过一系列复杂的机制影响肾功能,如诱导转化生长因子-β（TGF-β）产生;刺激血管紧张素Ⅱ及血管紧张素转换酶的产生等。     

阿魏酸钠对糖尿病肾病的保护作用及机制

目的：观察阿魏酸钠对糖尿病肾病伴高脂血症患者血脂、内皮素、一氧化氮、24h尿蛋白的影响。方法：将60例糖尿病肾病伴高脂血症患者随机分为治疗组（30例）和对照组（30例）,两组基础治疗相同,治疗组在对照组基础治疗上加用阿魏酸钠,治疗4周后观察两组患者血脂、内皮素、一氧化氮、24h尿蛋白及临床症状的变化。结果：与对照组比较,治疗组在降低总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、内皮素（endothelin,ET）、24h尿蛋白和升高一氧化氮（nitric oxide,NO）方面疗效更为显著,两组升高高密度脂蛋白胆固醇（HDL-C）的疗效相似。结论：阿魏酸钠可有效调节糖尿病肾病伴高脂血症患者血脂水平,改善内皮功能,降低尿蛋白,对糖尿病肾病有保护作用。     

联用阿魏酸钠和维拉帕米治疗老年糖尿病肾病观察

糖尿病肾病的治疗已取得了一些成就,但是老年糖尿病肾病(EDN)仍然是临床治疗的难题,笔者在西医常规治疗的基础上,联合运用阿魏酸钠和维拉帕米治疗老年糖尿病肾病31例,并进行了对照观察,兹报道如下.     

一氧化氮在糖尿病肾病中的作用

目的探讨糖尿病（ＤＭ）和高血压大鼠肾脏一氧化氮（ＮＯ）途径与ＤＭ肾病的关系。方法将自发性高血压大鼠（ＳＨＲ）制成链脲佐菌素（ＳＴＺ）ＤＭ模型。设ＷＫＹ、ＳＨＲ和ＳＨＲＤＭ三组。除形态学观察外,还测定各组大鼠肌酐清除率（Ｃｃｒ）、２４小时尿蛋白、血及肾组织ＮＯ含量、肾脏ＮＯ合成酶（ＮＯＳ）活性和ＮＯＳｍＲＮＡ表达水平。结果ＳＨＲＤＭ组大鼠２４小时尿蛋白定量２０周时明显高于其余两组,Ｃｃｒ无明显改变。血ＮＯ水平升高,肾ＮＯ含量降低。肾脏结构型ＮＯＳ（ｃＮＯＳ）活性下降,诱导型ＮＯＳ（ｉＮＯＳ）活性或ｉＮＯＳ／ｃＮＯＳ（ｉ／ｃ）比值增加。肾小球ＮＯＳｍＲＮＡ表达面积扩大,入球动脉及小叶间动脉ＮＯＳ基因表达明显下降。肾小球系膜增生,有形成ＫＷ结节或纤维蛋白帽的趋势,系膜区基质增多,基底膜增厚,肾小动脉壁厚腔窄。结论（１）ＳＴＺＳＨＲＤＭ模型出现的２４小时尿蛋白增加、肾小球系膜及肾小血管病变提示ＤＭ肾病的产生;（２）肾脏ＮＯ系统异常与ＤＭ肾病有关。     

抗氧化剂在糖尿病肾病进展和治疗中的作用

正糖尿病肾病(diabetic kidney disease,DKD)是糖尿病主要的并发症之一,也是导致终末肾疾病(end-stage of renal disease,ESRD)的主要原因[1]。DKD的发病机制较多,但高血糖所致的代谢异常进而引发的肾内细胞调节异常是导致肾组织不间断损害的主要原因之一[2]。目前研究发现,氧化应激产物参与了DKD的多种发病机制[3],提示在复杂的DKD发病机制     

阿魏酸钠与依那普利联用治疗早期糖尿病肾病临床观察

糖尿病肾病(diabetic nephropathy,DN)是糖尿病(diabetes mellitus,DM)最常见的并发症之一,目前全球DM病人已达1.5亿,预测2025年可达3亿,有40%的DM发展为DN[1].本病的重点在于早期治疗,早期预防.笔者用阿魏酸钠与依那普利联用治疗早期DN,效果较好,现报道如下.     

galectin-3在糖尿病肾病中的作用

随着分子生物学、分子免疫学、细胞信号转导理论等领域的进展，有关晚期糖基化产物（advanced glycation end products，AGE）及其受体的结构及对糖尿病肾病（DN）作用的研究也逐步深入。galectin-3即AGE-R3，是AGE的受体之一，与OST-48（AGE-R1）、80K-H（AGE-R2）一起在糖尿病肾病（DN）的发生发展中发挥了重要作用。本文对此作一综述。     

内皮素在糖尿病肾病中的作用研究

糖尿病肾病时具有血浆、肾脏局部及尿液内皮素 (ET)含量变化。ET通过干扰正常血糖代谢、影响体内其他细胞因子与生长因子以及改变肾脏血流动力、调节水盐代谢等机理参与糖尿病肾病的发生与进展。     

炎症在糖尿病肾病发病中的作用

糖尿病肾病的发病受多方面因素影响，越来越多的证据显示炎症在糖尿病肾病的发生发展中起重要作用。本文对炎症在糖尿病肾病发病中的作用作一综述。     

Role of lipid control in diabetic nephropathy

Patients with diabetic nephropathy are known to be associated with many lipoprotein abnormalities, including higher plasma levels of very low-density lipoprotein, low-density lipoprotein and triglycerides, and lower levels of high-density lipoprotein. Many studies have reported that lipids may induce both glomerular and tubulointerstitial injury through mediators such as cytokines, reactive oxygen species, chemokines, and through hemodynamic changes. Clinical studies in patients with diabetic nephropathy showed that lipid control can be associated with an additional effect of reduction in proteinuria. Experimental studies demonstrated that lipid-lowering agents exerted a certain degree of renoprotection, through both indirect effects from lipid lowering and a direct effect on cell protection. Therefore, lipid control appears to be important in the prevention and treatment of diabetic nephropathy. Diabetic nephropathy has become the leading cause of end-stage renal failure in many countries, including Taiwan. One of the major risk factors for the development and progression of diabetic nephropathy is dyslipidemia. In this paper we will review the role of lipid in mediating renal injury and the beneficial effects of lipid control in diabetic nephropathy.     

Role of oxidative stress in diabetic nephropathy

Accumulating research suggests that oxidative stress is a significant contributor to the pathogenesis of diabetic nephropathy. The normal kidney generates a substantial amount of oxidative stress because of its high metabolic activity that is balanced by an extensive antioxidant system. However, in pathologic states such as hyperglycemia, nitroso-oxidant balance shifts toward a pro-oxidant state that accelerates tissue and vascular injury. This oxidative damage progresses concomitant with worsening glucose metabolism, vascular dysfunction, and kidney disease. Accordingly, strategies to reduce oxidative stress in diabetes mellitus may exert favorable effects on the progression of diabetic nephropathy.     

Role of nitric oxide in diabetic nephropathy

Diabetic nephropathy is the leading cause of end-stage renal disease in the Western hemisphere. Endothelial dysfunction is the central pathophysiologic denominator for all cardiovascular complications of diabetes including nephropathy. Abnormalities of nitric oxide (NO) production modulate renal structure and function in diabetes but, despite the vast literature, major gaps exist in our understanding in this field because the published studies mostly are confusing and contradictory. In this review, we attempt to review the existing literature, discuss the controversies, and reach some general conclusions as to the role of NO production in the diabetic kidney. The complex metabolic milieu in diabetes triggers several pathophysiologic mechanisms that simultaneously stimulate and suppress NO production. The net effect on renal NO production depends on the mechanisms that prevail in a given stage of the disease. Based on the current evidence, it is reasonable to conclude that early nephropathy in diabetes is associated with increased intrarenal NO production mediated primarily by constitutively released NO (endothelial nitric oxide synthase [eNOS] and neuronal nitric oxide synthase [nNOS]). The enhanced NO production may contribute to hyperfiltration and microalbuminuria that characterizes early diabetic nephropathy. On the other hand, a majority of the studies indicate that advanced nephropathy leading to severe proteinuria, declining renal function, and hypertension is associated with a state of progressive NO deficiency. Several factors including hyperglycemia, advanced glycosylation end products, increased oxidant stress, as well as activation of protein kinase C and transforming growth factor (TGF)-beta contribute to decreased NO production and/or availability. These effects are mediated through multiple mechanisms such as glucose quenching, and inhibition and/or posttranslational modification of NOS activity of both endothelial and inducible isoforms. Finally, genetic polymorphisms of the NOS enzyme also may play a role in the NO abnormalities that contribute to the development and progression of diabetic nephropathy.     

Role of the renin angiotensin system in diabetic nephropathy

Diabetic nephropathy has been the cause of lot of morbidity and mortality in the diabetic population. The renin angiotensin system (RAS) is considered to be involved in most of the pathological processes that result in diabetic nephropathy. This system has various subsystems which contribute to the disease pathology. One of these involves angiotensin II (Ang II) which shows increased activity during diabetic nephropathy. This causes hypertrophy of various renal cells and has a pressor effect on arteriolar smooth muscle resulting in increased vascular pressure. Ang II also induces inflammation, apoptosis, cell growth, migration and differentiation. Monocyte chemoattractant protein-1 production responsible for renal fibrosis is also regulated by RAS. Polymorphism of angiotensin converting enzyme (ACE) and Angiotensinogen has been shown to have effects on RAS. Available treatment modalities have proven effective in controlling the progression of nephropathy. Various drugs (based on antagonism of RAS) are currently in the market and others are still under trial. Amongst the approved drugs, ACE inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. ARBs are shown to be superior to ACE inhibitors in terms of reducing proteinuria but the combined role of ARBs with ACE inhibitors in diabetic nephropathy is under debate.     

黄腐酸钠对实验性糖尿病大鼠肾脏的保护作用

目的研究黄腐酸钠对糖尿病大鼠肾脏病变的保护作用及其机制。方法观察黄腐酸钠对肾小球形态，肾小球基底膜超微结构，尿白蛋白排出率的影响及血浆组织型纤溶酶原激活剂（ｔＰＡ）、纤溶酶原激活剂抑制物（ＰＡＩ１）活性改变。结果糖尿病大鼠血浆ｔＰＡ活性明显降低，而ＰＡＩ１活性升高。黄腐酸钠明显降低糖尿病大鼠尿白蛋白，抑制肾小球肥大，延缓肾小球基底膜增厚及足突融合，显著提高血浆ｔＰＡ活性而降低ＰＡＩ１活性。结论黄腐酸钠对糖尿病肾病具有保护作用。此作用可能与提高血浆纤溶活性有关。     

切应力在糖尿病肾病发病机制中的作用研究

糖尿病肾病是糖尿病的慢性并发症之一,其发病机制尚不清。切应力是液体沿管腔长轴方向对管壁施加的作用力。切应力作用于肾小球内皮细胞和肾小管上皮细胞,调节一系列细胞因子的表达和信号通路的传导,参与糖尿病肾病的发生发展。     

胰岛素抵抗在糖尿病肾病发生、发展中的作用研究进展

糖尿病肾病(diabetic nephropathy,DN)是导致终末期肾衰的常见原因.胰岛素抵抗(insulin resistance,IR)是其常见的病理生理表现.在本综述中,我们对IR在DN发生中的作用进行了深入讨论.研究表明,高胰岛素血症可通过直接的肾脏细胞损伤、促进生长因子作用、激活肾内RAS系统、增加内皮索...