促红细胞生成素干预肾缺血再灌注损伤后肾小管间质的纤维化

背景：促红细胞生成素能减轻炎症反应、抗凋亡以及对缺血再灌注肾损伤有保护性作用。目的：分析促红细胞生成素对肾缺血再灌注损伤后细胞凋亡和肾小管间质纤维化的关系。方法：通过单侧肾缺血再灌注损伤构建患侧肾小管间质纤维化模型。实验小鼠随机分为4组：假手术组、缺血再灌注组、促红细胞生成素低剂量组和促红细胞生成素高剂量组。苏木精-伊红、Masson染色观察肾脏病理改变,免疫组织化学检测肾组织中Bcl-2和Bax蛋白表达水平,Western blot检测Caspase-3的表达。结果与结论：与缺血再灌注组相比,两促红细胞生成素干预组肾小管和间质病变减轻。缺血再灌注组和两促红细胞生成素干预组肾脏Bcl-2和Bax表达均较假手术组明显上调,但缺血再灌注组更明显;缺血再灌注组Bcl-2/Bax比值较假手术组低,而两促红细胞生成素干预组Bcl-2/Bax比值却较缺血再灌注组高;两促红细胞生成素干预组Caspase-3表达高于假手术组而低于缺血再灌注组。结果表明,肾缺血再灌注损伤后期肾小管间质纤维化进程与细胞凋亡相关,Bcl-2/Bax及Caspase-3起了重要作用;低剂量促红细胞生成素也能减轻小鼠肾缺血再灌注损伤后期肾小管间质纤维化程度。     

促红细胞生成素对急性肾损伤中干细胞因子及其受体表达的影响

背景：细胞因子在减轻肾脏缺血再灌注损伤中的作用日益受到重视,干细胞因子具有造血系统以外的器官保护作用。目的：探讨大鼠急性肾损伤模型中干细胞因子及其受体c-Kit表达的变化和促红细胞生成素预处理对其表达的影响。方法：成年雄性Wistar大鼠34只,采用夹闭双侧肾蒂建立缺血再灌注模型,缺血45 min后再灌注24 h,随机分为假手术组（n=10）、缺血再灌注组（n=12）和促红细胞生成素组（n=12）,促红细胞生成素组于造模前2 h一次性尾静脉注射重组人促红细胞生成素5 000 U/kg。免疫组化及图像分析技术检测各组肾组织中干细胞因子及c-Kit的表达变化,测定血清肌酐和尿素氮水平,苏木精-伊红染色观察肾组织病理学改变并计算肾小管损伤积分。结果与结论：干细胞因子及c-Kit在肾组织中的表达仅限于肾小管区域。与假手术组比较,干细胞因子和c-Kit在缺血再灌注组和促红细胞生成素组的表达均明显增高（P 〈 0.05）,促红细胞生成素组干细胞因子表达高于缺血再灌注组（P 〈 0.01）,但两组c-Kit表达差异无显著性意义（P 〉 0.05）;促红细胞生成素组血清肌酐与尿素氮水平明显低于缺血再灌注组（P 〈 0.05）,但高于假手术组（P 〈 0.05）。与缺血再灌注组比较,促红细胞生成素组肾组织病变减轻。说明缺血再灌注导致急性肾损伤发生时干细胞因子及c-Kit表达升高,而促红细胞生成素对急性肾损伤的保护作用可能与上调干细胞因子及c-Kit表达有关。     

ARNT基因失活小鼠的肾脏缺血再灌注损伤

背景:如何有效防治肾脏的缺血再灌注损伤,一直是肾移植领域的研究重点。但目前其机制仍然不是很清楚。目的:探讨缺氧诱导因子系统对小鼠肾缺血再灌注损伤的影响及可能的作用机制。方法:选取两种小鼠,一种为芳香族碳氢化合物核转移子(aryl hydrocarbon receptor nuclear translocator,ARNT)基因敲除小鼠,一种为同窝对照组小鼠。每种小鼠分别进行假手术、缺血再灌注、缺血再灌注时注射重组人促红细胞生成素、缺血再灌注时注射等量生理盐水。建立小鼠肾脏缺血再灌注损伤模型,分别比较再灌注损伤后1h血清促红细胞生成素含量、24h血清肌酐值、肾组织PAS染色肾小管损伤评分和TUNEL法计算肾小管细胞凋亡数。结果与结论:再灌注后1h血清促红细胞生成素水平ARNT敲除组明显低于对照组(P<0.01)。24h血清肌酐水平ARNT敲除组明显高于对照组(P<0.01)。ARNT敲除组明显比对照组损伤程度重,肾小管评分明显高于对照组(P<0.01)。ARNT敲除组阳性凋亡细胞数明显多于ARNT+/+组(P<0.01)。补充促红细胞生成素后,ARNT敲除组与对照组比较,差异无显著性意义(P>0.05)。结果表明,缺氧诱导因子系统对肾脏缺血再灌注损伤有重要的保护作用。可能是促红细胞生成素来介导其最大的保护效应。     

ARNT基因失活小鼠的肾脏缺血再灌注损伤

背景：如何有效防治肾脏的缺血再灌注损伤,一直是肾移植领域的研究重点。但目前其机制仍然不是很清楚。目的：探讨缺氧诱导因子系统对小鼠肾缺血再灌注损伤的影响及可能的作用机制。方法：选取两种小鼠,一种为芳香族碳氢化合物核转移子（aryl hydrocarbon receptor nuclear translocator,ARNT）基因敲除小鼠,一种为同窝对照组小鼠。每种小鼠分别进行假手术、缺血再灌注、缺血再灌注时注射重组人促红细胞生成素、缺血再灌注时注射等量生理盐水。建立小鼠肾脏缺血再灌注损伤模型,分别比较再灌注损伤后1h血清促红细胞生成素含量、24h血清肌酐值、肾组织PAS染色肾小管损伤评分和TUNEL法计算肾小管细胞凋亡数。结果与结论：再灌注后1h血清促红细胞生成素水平ARNT敲除组明显低于对照组（P〈0.01）。24h血清肌酐水平ARNT敲除组明显高于对照组（P〈0.01）。ARNT敲除组明显比对照组损伤程度重,肾小管评分明显高于对照组（P〈0.01）。ARNT敲除组阳性凋亡细胞数明显多于ARNT＋/＋组（P〈0.01）。补充促红细胞生成素后,ARNT敲除组与对照组比较,差异无显著性意义（P〉0.05）。结果表明,缺氧诱导因子系统对肾脏缺血再灌注损伤有重要的保护作用。可能是促红细胞生成素来介导其最大的保护效应。     

远期缺血预适应激活热休克蛋白27、促红细胞生成素、血红素加氧酶1对肾脏缺血再灌注损伤的影响

背景:缺血再灌注损伤是临床导致急性肾衰竭等其他疾病的重要原因,其机制为多因素、多途径的复杂的病理过程。目的:观察肾脏进行预处理后激活热休克蛋白、促红细胞生成素和血红素加氧酶1对肾脏缺血再灌注损伤的影响。方法:雄性C57BL/6小鼠90只随机分成3组。缺血再灌注组为右肾切除,左肾缺血25min再灌注24h;预适应组为双侧肾脏缺血20min再灌注8d后再进行缺血再灌注。假手术组开腹游离肾蒂。结果与结论:血清肌酐和尿素氮检测预适应组和假手术组明显低于缺血再灌注组(P<0.01);MPO染色发现缺血再灌注组大量中性粒细胞浸润(P<0.01);PAS染色发现预适应组肾组织病理情况轻于缺血再灌注组(P<0.05);TUNEL染色分析结果表明预适应组和假手术组细胞凋亡数明显少于缺血再灌注组(P<0.01);预适应组热休克蛋白27mRNA表达明显高于缺血再灌注和假手术组(P<0.05),热休克蛋白27mRNA于第8天时最强,促红细胞生成素、血红素加氧酶1mRNA在24～48h达到峰值A,然后逐渐下降,第8天后达到峰值B,B>A,并且高于假手术组(P<0.01)。提示远期缺血预适应激活热休克蛋白27、促红细胞生成素、血红素加氧酶1,能减少炎症因子浸润、促进肾小管细胞修复和抑制细胞凋亡从而参与肾脏内源性保护机制。     

促红细胞生成素对肾缺血再灌注氧化应激损伤的影响

目的:探讨重组人促红细胞生成素对肾缺血再灌注损伤的作用及机制。方法:实验于2005-07/2006-01在泸州医学院中心实验室和病理生理实验室完成。选择雄性Wistar大鼠54只,建立右肾切除,左肾肾动脉夹闭45min后再灌注的动物模型,将54只大鼠随机数字表法分为左肾未缺血再灌注组18只,切除右肾,不夹闭左肾动脉。重组人促红细胞生成素干预组18只,在再灌注开始前5min静脉注射重组人促红细胞生成素(3000U/kg)。肾缺血再灌注损伤组18只,在再灌注开始前5min注射等量的生理盐水。各组再灌注达1,6,24h时间点检测肾功能(血肌酐,尿素氮),并观察肾组织中丙二醛含量、超氧化物歧化酶活性和组织形态学改变。结果:纳入动物54只,均进入结果分析。①重组人促红细胞生成素干预组肾组织中丙二醛含量与肾缺血再灌注损伤组相比显著降低、超氧化物歧化酶活性显著升高[以再灌注6h为例,分别为(0.93±0.09),(1.19±0.08)μmol/g,(1919.55±126.52),(1338.10±5.50)μkat/g,P<0.05]。②重组人促红细胞生成素干预组血肌酐、尿素氮含量与肾缺血再灌注损伤组相比降低[以再灌注6h为例,分别为(87.53±1.22),(121.63±21.17)μmol/L,(252.06±4.59),(369.14±18.38)mg/L,P<0.05]。③重组人促红细胞生成素干预组肾脏病变与肾缺血再灌注组比较明显减轻,肾小管上皮细胞轻度水肿,基底膜多完整,肾小管腔内见少量管型。结论:重组人促红细胞生成素能减轻肾缺血再灌注损伤,其机制可能是抗氧自由基损伤,提高内源性抗氧化能力。     

头针对急性脑缺血再灌注大鼠的保护作用

目的:探讨头针对急性脑缺血损伤的保护作用及机制。方法:将90只健康SD雌性大鼠随机分为假手术组10只、模型组40只、头针组40只,采用线栓法制备大脑中动脉阻塞(MCAO)再灌注模型,假手术组不造成缺血状态,头针组行头针治疗,于再灌注6、24、487、2 h时采用神经功能缺损量表(NSS)评定各组大鼠神经功能、TUNEL法检测各组神经细胞凋亡率,Western blot和RT-PCR检测脑组织Caspase-3、Bcl-2、Bax的表达。结果:头针组再灌注72 h NSS评分显著低于模型组(P<0.01);模型组缺血侧神经细胞凋亡率随再灌注时间延长而增加,24 h达高峰;头针组神经细胞凋亡率明显低于模型组,以244、8 h尤为显著。再灌注6 h后Bcl-2、Bax蛋白在缺血侧脑组织中均有表达,24 h达高峰,但随着时间推移,头针组Bcl-2/Bax比值减少较模型组慢;头针组的Bcl-2、Caspase-3 mRNA的表达较模型组比较均有统计学差异(P<0.05)。结论:脑缺血可诱导Bcl-2、Bax、Caspase-3基因表达增强;头针对缺血脑组织具有保护作用,可能通过抑制细胞凋亡、减轻脑缺血再灌注损伤来实现。     

阿魏酸钠预处理对急性缺血-再灌注损伤大鼠心肌细胞凋亡的影响

目的 探讨阿魏酸钠对急性缺血-再灌注损伤大鼠心肌细胞凋亡的保护机制.方法 实验大鼠随机分为假手术组、急性心肌缺血-再灌注组(模型组)及阿魏酸钠低剂量预先给药组(55 mg/kg)和阿魏酸钠高剂量预先给药组(110 mg/kg).采用阻断大鼠左冠状动脉前降支40 min,再灌注180 min的方法,制备急性心肌缺血-再灌注损伤模型.低剂量、高剂量组分别于缺血前30 min通过尾静脉注射55 mg/kg及110 mg/kg阿魏酸钠,假手术组、模型组注射等容积生理盐水.分别检测各组血清肌钙蛋白Ⅰ (cTnI)及血浆氨基末端脑钠肽前体(NT-proBNP)浓度;TUNEL法检测心肌细胞凋亡程度;Western blotting检测心肌细胞凋亡相关蛋白Bcl-2、Bax和Caspase-3的表达.结果 与假手术组比较,缺血-再灌后各组大鼠的cTnI及NT-proBNP明显升高(均P＜0.01).与模型组及低剂量组比较,高剂量组cTM及NT-proBNP明显降低(P＜0.01);心肌细胞凋亡指数明显降低(P＜0.01);促凋亡基因Bax和Caspase-3表达受到抑制,而抗凋亡基因Bcl-2的表达明显升高(P＜0.01).低剂量组与模型组比较差异无统计学意义(P＞0.05).结论 高剂量阿魏酸钠预处理对缺血-再灌注损伤大鼠的心功能有明显的保护作用,其机制与抑制心肌细胞凋亡有关.     

黄芪当归合剂对大鼠缺血性急性肾损伤的保护研究

目的:探讨黄芪当归合剂对实验性缺血性肾损伤大鼠肾小管上皮细胞凋亡的保护作用.方法:建立大鼠实验性缺血性急性肾损伤模型,在缺血30 min再灌注不同时间点检测血尿素氮(BUN)、血肌酐(SCr)和尿液中N-乙酰-β-D-氨基葡萄糖酐酶(NAG).同时取肾组织,苏木素-伊红(HE)染色,光镜下观察细胞形态学变化.免疫组织化学方法检测Bcl-2和Bax基因的蛋白表达,观察黄芪当归合剂对上述表达的影响.结果:缺血性急性肾损伤时肾脏存在明显的细胞凋亡;Bcl-2和Bax基因的蛋白表达主要在近曲肾小管和远曲肾小管,肾小球很少;肾脏缺血性损伤时Bcl-2基因表达增加,Bax基因表达中量增加,Bcl-2/Bax比率升高.与缺血/再灌注组比较,黄芪当归合剂组Bax表达明显增加,Bcl-2/Bax比率降低,肾脏损伤亦减轻.结论:黄芪当归合剂对急性肾损伤具有显著的保护作用,其机制可能与其降低Bcl-2/Bax比率有关.     

局灶性脑缺血再灌注损伤模型大鼠与促红细胞生成素的神经保护作用

背景:近年来动物实验和体外细胞培养研究证实促红细胞生成素对脑缺血具有神经保护作用,有关促红细胞生成素脑保护的作用机制目前尚未阐明.目的:通过观察缺血损伤区域脑组织细胞学形态,检测脑组织超氧化物歧化酶、丙二醛浓度,探讨促红细胞生成素对脑缺血再灌注损伤的保护作用.方法:采用线栓法建立Wistar大鼠局灶性缺血再灌注损伤模型,分别于缺血后2 h腹腔注射生理盐水3 000 U/kg、促红细胞生成素3 000,1 000 U/kg,并设假手术组.缺血再灌注损伤24 h后,应用苏木精-伊红染色法检测大鼠脑组织病理学变化,应用黄嘌呤氧化酶法和硫代巴比妥酸法分别测定超氧化物歧化酶活性和丙二醛浓度.结果与结论:形态学结果显示促红细胞生成素高剂量组较生理盐水组皮质神经细胞存活数量增多,损伤程度减轻;促红细胞生成素高、低剂量组超氧化物歧化酶活性均明显高于假手术组和生理盐水组(P<0.05),丙二醛浓度明显低于假手术组和生理盐水组(P<0.05);促红细胞生成素高剂量组超氧化物歧化酶活性明显高于促红细胞生成素低剂量组,丙二醛含量明显低于促红细胞生成素低剂量组(P<0.05).提示经腹腔注射促红细胞生成素,可使大鼠脑缺血再灌注损伤区神经细胞存活数量明显增加,可显著改善组织的病理学改变,其保护作用可能是通过促红细胞生成素清除自由基,拮抗过氧化损伤实现的.     

Ruptured renal angiomyolipoma presenting as renal colic

The case of a patient with acute onset of flank pain and hematuria is presented. Initial therapy was directed toward relief of pain believed to be caused by renal colic. It was not until the patient developed atypical features that the true diagnosis, ruptured renal angiomyolipoma, was discovered. The case and discussion emphasize the need to carefully consider a complete differential diagnosis when evaluating patients with flank pain and hematuria who have atypical clinical features or an atypical course.     

Functional renal imaging: nonvascular renal disease

Functional renal imaging—a fast-growing field of MR-imaging—applies different sequence types to gather information about the kidneys other than morphology and angiography. This update article presents the current status of different functional imaging approaches and presents current and potential clinical applications. Apart from conventional in-phase and opposed-phase imaging, which already yields information about the tiusse composition, BOLD (blood-oxygenation level dependent) sequences, DWI (diffusion-weighted imaging) sequences, perfusion measurements, and dedicated contrast agents are used.     

Cortical renal leiomyoma with extension to renal pelvis

We describe a case of renal leiomyoma in a 21-year-old woman who presented with flank pain and hematuria. Urographic and computed tomographic (CT) studies revealed a large right renal mass with polypoid outgrowth protruding into the renal pelvis. Cortical renal leiomyoma with this radiographic manifestation is extremely rare.     

Epidemiology of renal recovery after acute renal failure

PURPOSE OF REVIEW: Recovery of renal function after acute renal failure is an important clinical determinant of patient morbidity. Herein, the epidemiology of renal recovery after acute renal failure will be described, along with potential predictive factors and interventions. RECENT FINDINGS: Renal recovery has been variably defined, most often as recovery to independence from renal replacement therapy. A recent consensus definition for acute renal failure has been published and included provisions for defining renal recovery. Renal recovery to renal replacement therapy independence occurs in the majority by hospital discharge and peaks by 90 days. All of older age, female sex, co-morbid illnesses, especially chronic kidney disease, and late initiation of renal replacement therapy or conventional intermittent renal replacement therapy have been coupled with non-recovery. Analysis of the literature suggests several interventions may influence recovery. SUMMARY: The prognosis is generally good for recovery after acute renal failure. Most patients will be independent of renal replacement therapy by 90 days. Additional research is necessary, however, to understand recovery rates not only to independence from renal replacement therapy, but also to complete and partial recovery. Future studies need to consider the health economic implications for survival and non-recovery. Finally, questions on the role of various interventions require characterization in randomized controlled trials to determine how they may influence renal prognosis.     

急性肾功能损伤与衰竭生物标志物

急性肾功能损伤（ARI）与急性肾功能衰竭（ARF）是加强医疗病房（ICU）的常见疾病．ICU中80％的ARF由急性肾小管损伤所致，而非肾小球或间质性病变引起。其死亡率较高，寻找敏感性和特异性较好的ARI或ARF生物标志物，对早期诊断、治疗和改善预后有着重要意义。本文介绍和评估了ARI或 ARF生物标志物的研究现状。并展望了其未来的前景。[第一段]     

Biomarkers of acute renal injury and renal failure

Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes (alpha- and pi-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, gamma-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins (alpha1- and beta2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.     

Cardiac enzymes, renal failure and renal transplantation

Diagnostic accuracy of the currently available serum markers of cardiac injury, such as myoglobin, creatine kinase and its myocardial isoform, are altered in patients with renal failure. It is shown that cardiac troponins have decreased diagnostic sensitivity and specificity in patients receiving renal replacement therapy. Data regarding serum levels of these cardiac biomarkers, especially those of the cardiac troponins, in patients with a transplanted kidney are limited. Current data show that levels of cardiac troponin I are unaltered in patients who have undergone renal transplantation, while levels of cardiac troponin T may be elevated.We believe that cardiac troponin I should be the biomarker of choice for diagnosis of myocardial injury in these patients. However, further trials are required for conclusive results.     

Preservation of renal function in chronic renal failure.

Mechanisms of progression of chronic renal failure (CRF) have been well documented in the rat but may not be relevant in man. Factors which may modify clinical CRF include underlying disease, diet, hypertension, intercurrent events, and adverse or beneficial effects of drug therapy. It has been argued that progression in many forms of renal disease is inexorable below a certain level of renal function. In other diseases, eg primary malignant hypertension, analgesic nephropathy, function frequently improves in both the short and long term with appropriate management. Thus knowledge of the nature of the underlying disease is essential in assessing progression. The value of diet in preserving renal function has been debated, particularly the relative roles of protein and phosphate control. In our own unit, a prospective randomized study showed a benefit of protein restriction. Development of accelerated hypertension is an important cause of progression of renal disease and clinical and experimental evidence supports the view that non-accelerated hypertension is also a factor in progression, amenable to treatment. Various intercurrent events may accelerate progression and function may be lost permanently following sepsis, urinary tract obstruction, renal arterial or venous obstruction, hypotension and in some cases pregnancy. Numerous drugs can have deleterious effects on the kidney. The possibility that converting enzyme inhibitors might preserve renal function is attracting attention but in view of their side effects their place in therapy should be determined by prospective controlled studies in which the above factors are carefully considered.