前列腺素E1脂微球载体制剂对多柔比星肾病大鼠结缔组织生长因子表达的影响

目的研究多柔比星肾病大鼠肾组织中结缔组织生长因子(CTGF)表达,同时探讨前列腺素E1脂微球载体制剂(Lipo-PGE1)对其表达的影响.方法 将24只雌性SD大鼠(体重180～200 g)随机分为对照组、多柔比星肾病模型组和多柔比星肾病Lipo-PGE1治疗组3组.采用尾静脉一次性注射多柔比星7.5 mg/kg的方法建立多柔比星肾病动物模型,第8周开始Lipo-PGE1治疗组给予尾静脉注射Lipo-PGE1,用量200 μg/(kg*d).10周后处死全部大鼠,并观察肾组织病理改变,应用免疫组织化学方法和原位杂交技术检测CTGF在肾组织中的表达. 结果 Lipo-PGE1治疗组大鼠肾小球硬化及基质增生程度比多柔比星肾病组明显减轻,免疫组织化学染色及原位杂交结果显示多柔比星肾病组较正常对照组肾小球和肾小管区CTGF蛋白及CTGFmRNA表达量明显增加(P<0.05).Lipo-PGE1治疗组肾小球和肾小管间质CTGF蛋白及CTGFmRNA表达量明显低于多柔比星肾病组(P<0.05).结论 多柔比星肾病组大鼠第10周肾小球及肾小管间质尤其是肾小管间质区CTGF蛋白及CTGFmRNA表达量明显增加.Lipo-PGE1延缓多柔比星肾病肾损害,其机制可能与通过下调CTGF的表达有一定关系,并且可能通过减少肾小球内细胞增生和细胞外基质(ECM)沉积,延缓慢性肾脏疾病的进展.     

二子合剂对糖尿病大鼠肾脏的保护作用

目的：探讨富含木脂素成分的中药牛蒡子、五味子组成的二子合剂对糖尿病大鼠肾脏的保护作用。方法：将SD大鼠建成链脲佐菌素诱导的糖尿病模型，设正常对照组、模型对照组、苯那普利治疗组、二子合剂大剂量治疗组及小剂量治疗组．4周后检测血糖、24h尿量、尿蛋白总量、尿白蛋白总量、血胆固醇、尿ET-1、TNF-α及肾组织病理变化。结果：与模型对照组相比，苯那普利组及二子合剂大剂量治疗组各项检测指标均有改善，两疗效近似。二子合剂小剂量治疗组仅见尿白蛋白总量及毛细血管襻面密度有减少。结论：牛蒡子、五味子合剂对糖尿病肾脏损害有一定的保护作用，其作用与剂量有相关性。     

Urinary excretions of lipocalin-type prostaglandin D2 synthase predict the development of proteinuria and renal injury in OLETF rats.

BACKGROUND: Otsuka Long-Evans Tokushima Fatty (OLETF) rats genetically develop diabetes which is associated with hypertension. In preliminary studies, urinary excretions of L-PGDS (lipocaline-type prostaglandin D synthase) increase before diabetic nephropathy obviously develops, and this may predict progression of renal injury following diabetes. In the present study, we attempted to define whether urinary excretions of L-PGDS behave as the predictor of development of diabetic nephropathy in OLETF rats. METHODS: We investigated alterations of urinary L-PGDS excretions during the establishment of diabetes and assessed the relationship between the L-PGDS excretions and renal function in OLETF rats. Furthermore, we treated OLETF rats with troglitazone and analysed the effects on L-PGDS metabolisms. Urinary L-PGDS was measured by immunoenzyme assay and the occurrence of L-PGDS and its mRNA in the kidney was assessed by immunohistochemistry and a PCR method. RESULTS: Urinary excretions of L-PGDS were significantly higher in OLETF rats than non-diabetic Long-Evans Tokushima Otsuka (LETO) rats. The excretions age-dependently increased in OLETF and this increase appeared to be due to increased glomerular permeability to L-PGDS. Messenger RNA and antigenicity of L-PGDS were demonstrated in renal tissue; however, the de novo synthesis of L-PGDS mRNA seemingly contributed to urinary L-PGDS excretions much less than glomerular filtration. Multiple regression analysis revealed that urinary L-PGDS was determined by urinary protein excretions, and not by high blood pressure per se. Conversely, urinary proteinuria in the established diabetic nephropathy was predicted by urinary L-PGDS excretions in the early stage of diabetes. CONCLUSIONS: Urinary excretions of L-PGDS are likely to reflect the underlying increase in glomerular permeability. This property may be useful to predict forthcoming glomerular damage following diabetes in OLETF rats.     

抗氧化剂对糖尿病大鼠肾小球蛋白激酶C的影响

目的　通过大鼠糖尿病模型 ,观察抗氧化剂对糖尿病大鼠肾小球蛋白激酶的影响。方法　将 75只雄性Wistar大鼠分为正常对照组、糖尿病未治疗组、抗氧化剂治疗组各 2 5只 ,共观察 8周 ,分别测定尿白蛋白排泄量(UAE) ,内生肌酣消除率 (Ccr)、血浆及肾脏组织一氧化氮 (NO)、一氧化氮合成酶 (NOS)、内皮素 (ET)和肾小球蛋白激酶C(proteinkinaseC ,PKC)。结果　给予维生素E治疗组 8周时 ,Ccr[(5 .2 8± 0 .5 4)ml/(min·kg) ]及尿白蛋白排泄量 [(14.2 7± 1.16 ) μg/2 4h]显著低于未治疗组 ,肾小球细胞膜PKC[(6 8.2 7± 12 .33) pmol/(min·mgprotein) ],2周时N0 [(34 .2 3± 3.91) μmol/L]及NOS[(32 .0 7± 3.76 )U/L]明显低于未治疗组 ,维生素E治疗组 2周时与 8周时的NO及NOS下降幅度明显小于未治疗组。结论　维生素E具有抑制PKC活性作用。     

Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy.

BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients. METHODS: We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured. RESULTS: Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated. CONCLUSIONS: Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics.     

Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.     

Preemptive Retransplantation for BK Virus Nephropathy: Successful Outcome Despite Active Viremia

BK virus nephropathy (BKVN) is now recognized as a major cause of renal allograft loss. Recent reports suggest that retransplantation in patients with graft loss due to BKVN is safe after return to dialysis. Since early transplantation is associated with improved outcomes, it would be advantageous if this procedure could be performed prior to ultimate graft loss. However, little data are available regarding the safety of this approach during active viremia. In this report, we describe successful preemptive retransplantation with simultaneous allograft nephrectomy in two patients with active BKVN and viremia at the time of surgery. With 21- and 12-month follow-up, respectively, both patients have stable allograft function and no evidence for active viral replication. We conclude that preemptive retransplantation can be considered in patients with failing allografts due to BKVN.     

Partially Reversible Chronic Renal Failure Due to Long-term Use of Non-steroidal Anti-inflammatory Drugs

A case of partially reversible chronic renal failure due tolong-term NSAID use is discussed. An analysis of this and similarcases recently reported indicates many similarities betweenchronic NSAID nephropathy and analgesic nephropathy.     

大黄对实验性糖尿病大鼠肾脏肥大及高滤过作用的影响

肾脏肥大和高滤过是糖尿病肾病出现最早的病理生理特征。本研究利用中药大黄抑制糖尿病的肾脏肥大,试图达到控制其高滤过现象。实验结果表明,大黄能明显地抑制糖尿病肾脏肥大及其组织中蛋白质、DNA含量的增加;大黄治疗组的菊粉清除率明显低于非治疗组;此外,大黄还能使糖尿病血清甘油三酯、胆固醇水平降低。结论:大黄可以通过影响糖尿病肾病肾脏肥大,降低高滤过和纠正血脂代谢紊乱,治疗实验性糖尿病肾病动物模型。     

A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.