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PPAR为核激素受体超家族转录因子，能调节许多细胞代谢过程包括脂肪代谢、糖代谢、细胞周期、细胞分化、炎症和细胞外基质重塑等。肾脏组织中可检测出多种PPAR异构体。肾小球系膜细胞、髓质集合小管等都存在PPAR-γ。实验证实，应用PPAR-γ激动剂如罗格力酮、曲格力酮等，不仅可以改善异常代谢，还可以减轻某些肾脏病病变程度。糖尿病肾病、单侧输尿管结扎所致的梗阻性肾病等，应用罗格力酮可以减轻小管间质纤维化程度，降低TGF-β、MCP-1等表达。还观察到在由内皮素阻滞剂所致糖尿病肾病进展的保护机制中，PPAR-γ下游的抑制因子脂肪酸转运蛋白参与作用。
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【思考题】
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1．试述ACEI肾功能保护作用的非降压、非血流动力学机制。
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2．根据目前研究状况，在肾脏疾病慢性进展理论方面还可以进行哪些研究？
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参考文献
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[1] 陈灏珠主编．慢性肾功能衰竭．实用内科学．第12版．北京：人民卫生出版社，2005，2078.
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[2] Couser WG, Nangku M. Cellular and molecular biology of membranous nephropathy. J Nephrol, 2006, 19(6)
:699-705.
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[3] Nagase M, Yoshida S, Shibata S et al. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors. J Am Soc Nephrol, 2006, 17(12)
:3438-46.
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[4] Brewster UC, Perazella MA. The renin-angiotensin-aldosterone system and the kidney: effects on kidney disease. Am J Med, 2004, 116(4)
:263-72.
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[5] Kalluri R, Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest, 2003, 112(12)
:1776-84.
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[6] Nakanishi T, Ishigami Y, Otaki Y, et al. Impairment of vascular responses to reactive hyperemia and nitric oxide in chronic renal failure. Nephron, 2002, 92(3)
:529-35.
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[7] Suzuki T, Kimura M, Asano M, et al. Role of atrophic tubules in development of interstitial fibrosis in microembolism-induced renal failure in rat. Am J Pathol, 2001, 158(1)
:75-85.
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[8] De Muro P, Faedda R, Fresu P, et al. Urinary transforming growth factor-beta1 in various types of nephropathy. Pharmacol Res, 2004, 49(3)
:293-8.
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[9] Lu F, Li P, Zheng F, et al. Serum insulin-like growth factor 1 level and nutritional assessment in nondialytic patients with chronic renal failure. Kidney Blood Press Res, 2002, 25(2)
:116-9.
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[10] Richmond EJ, Uzri A, Rogol AD. The insulin-like growth factor system in kidney diseases. Nephron, 2001, 89(1)
:5-9.
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[11] Ambrosch A, Muller R, Freytag C, et al. Small-sized low-density lipoproteins of subclass B from patients with end-stage renal disease effectively augment tumor necrosis factor-alpha-induced adhesive properties in human endothelial cells. Am J Kidney Dis, 2002, 39(5)
:972-84.
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[12] Kobayashi E, Sasamura H, Mifune M, et al. Hepatocyte growth factor regulates proteoglycan synthesis in interstitial fibroblasts. Kidney Int, 2003, 64(4)
:1179-88.
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（陈伊伦）
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内科学新进展 第二节 延缓慢性肾功能衰竭进展策略
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摘 要 任何病因的肾脏疾病都会导致肾单位丢失，并产生蛋白尿、高血压、肾功能不全的临床综合征。RAS阻断可作为延缓慢性肾脏病（CKD）进展的基础治疗。目标血压＜130/80mm Hg; 蛋白尿＜0.5g/d应作为一个独立的治疗目标；尽管有争议，低蛋白饮食〔0.6g/(kg·d）〕对于CKD患者是合适的。高脂血症会加重CKD进展，治疗高脂血症可能改善肾功能；戒烟与血糖控制有助于延缓CKD进展。这些干预措施简单有效，将有效延缓肾功能衰竭，并减少终末期肾功能衰竭的发生率。
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Abstract Kidney disease of any cause all results in substantial loss of nephrons, characterised by hypertension, proteinuria and a progressive decline in renal function, Therefore, the use of renin-angiotensin-system（RAS）antagonists should be regarded as fundamental therapy for slowing the progression of CKD. Hypertension should be treated aggressively to achieve a blood pressure target of ＜130/80mmHg. Reduction of proteinuria to ＜0.5g/day should be regarded as an independent therapeutic goal. Although inconclusive, there is some evidence to support moderate dietary protein restriction to 0.6g/(kg·d）in CKD patients. Hyperlipidaemia may contribute to CKD progression and should be treated to reduce cardiovascular risk and potentially improve renal protection. Smoking cessation should be encouraged and, where necessary, assisted. Among diabetic patients tight glycaemic control should be achieved（glycosylated haemoglobin ＜7%). These interventions are simple and relatively inexpensive. If applied to all patients with CKD, they will result in substantial slowing of renal function deteriorations in many patients and thereby reduce the incidence of end-stage renal disease and require renal replacement therapy.
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慢性肾脏病（chronic kidney disease, CKD）是各种肾脏病于急性阶段未经控制后的共同转归，它是一种临床综合征。目前国际上公认的定义为：肾脏损害≥3个月，表现为下列之一者：肾脏病理异常和（或）尿成分异常（如有血尿、电解质异常、pH异常）和（或）影像学异常；或GFR＜60ml/(min·1.73m2)，有或无肾脏损害。慢性肾脏病一旦形成，常常以不同的速度发展、进行、直到终末期肾功能衰竭。长期的血液透析患者的快速增长给全世界各国卫生保健系统带来了巨大的负担，也占用了巨大的医疗资源。即使在完善的社会保健体系中，目前对于慢性肾功能不全的认识和治疗都还是远远不够的，肾功能衰竭的发病率在过去15年中成倍增长。虽然随着透析技术的明显进步，但慢性肾功能衰竭（CRF）临床长期透析患者的年死亡率仍高达20％以上。而且由于慢性肾脏病的持续进展的性质，以及平均年龄寿限的延长，糖尿病、动脉粥样硬化、心、脑血管事件等与慢性肾脏病有密切相关疾病的发病率上升，因此在原发病因治疗的基础上，应尽可能采用行之有效的综合治疗措施以延缓进展到终末期肾衰，是一件非常急迫的需要。近年来，随着对CRF发病机制研究的不断深入，在延缓CRF进行性恶化措施方面也取得了长足的进展。
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一、慢性肾功能衰竭进展的机制
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