曲尼司特对环孢素A慢性肾毒性大鼠肾间质骨桥蛋白表达及巨噬细胞浸润的影响

目的观察曲尼司特对环孢素A(CsA)慢性肾毒性大鼠肾功能及肾脏病理的影响。方法选取四川大学华西医院于2005年9月至2006年2月给低盐饮食SD大鼠灌胃20mg/(kg.d)剂量的CsA,制作大鼠CsA慢性肾毒性模型,同时喂饲400mg/(kg.d)剂量的曲尼司特。于治疗第1、2、4周末观察肾脏病理变化,并测定骨桥蛋白(OPN)、单核巨噬细胞抗原(ED1)的表达。结果曲尼司特能明显改善慢性CsA肾毒性大鼠的体重下降,减少肾小管上皮细胞空泡变性和细胞坏死及间质炎细胞浸润和间质纤维化,对肌酐清除率(Ccr)下降无明显影响;免疫组化结果显示曲尼司特治疗组大鼠肾小管-间质ED1阳性巨噬细胞数量及OPN表达较模型组显著减少(P<0.05)。结论曲尼司特能减轻CsA慢性肾毒性的肾脏病理损伤,这一防治作用与其减少ED1阳性巨噬细胞浸润及下调OPN表达有关。     

雷公藤甲素对Heymann肾炎模型足细胞病变的影响

目的利用被动型Heymann肾炎模型(passive Heymann nephritis, PHN)研究雷公藤甲素(triptolide)对膜性肾病的疗效及其对足细胞病变的影响. 方法实验动物分为正常对照组、PHN组和雷公藤甲素治疗组.雷公藤甲素(200 μg/kg·d)灌胃治疗,分别在观察7天、14天、21天和28天时宰杀大鼠,留取血清和尿标本,观察尿蛋白、血清白蛋白、肝酶、肌酐和外周血白细胞等指标的变化;留取肾组织标本,行光镜、免疫病理、电镜和免疫电镜检查,并对肾组织IgG、C5b-9沉积以及Nephrin和Podocin的分布进行观察. 结果(1)尿蛋白雷公藤甲素治疗7天即可显著降低PHN大鼠的蛋白尿,至14天、21天和28天时,治疗组大鼠的尿蛋白进一步降低,与Heymann肾炎大鼠之间差异有统计学意义(P＜0.01).在尿蛋白显著降低的同时,血浆白蛋白显著增加.(2)肾小球上皮侧免疫沉积物电镜观察结果显示,雷公藤甲素治疗组上皮侧免疫复合物、钉突以及基膜反应性增殖均较Heymann肾炎组似有所改善,治疗后上皮侧电子致密物减少,基膜反应减轻,但在尿蛋白明显减少的同时,上皮侧电子致密物始终存在.(3)肾小球IgG和C5b-9的沉积经雷公藤甲素治疗后肾小球IgG和C5b-9的沉积与Heymann肾炎大鼠相比,荧光强度有所减少,尤其在治疗后的第7天,减少较为明显.(4)足细胞病变经雷公藤甲素治疗7天、14天、21天和28天后,均可见足细胞的足突损伤比对照组明显减轻,足突融合显著改善,足突宽度显著降低,观察至第28天时,治疗组可见大部分足细胞的足突形态基本恢复正常.(5)足细胞裂孔膜蛋白的变化经雷公藤甲素治疗7天后,足细胞表面Nephrin和Podocin的表达比Heymann肾炎大鼠有明显增加,分布上的异常开始得到纠正,至第21天基本恢复成连续的线样分布.免疫电镜的结果再次显示了治疗后Nephrin的上述修复过程. 结论雷公藤甲素对被动型Heymann肾炎具有显著的治疗作用,能有效地减少蛋白尿,减轻肾组织免疫损伤,促进足细胞病变和裂孔膜蛋白结构的修复.雷公藤甲素疗效机制除了其免疫抑制和抗炎作用外,还与它能显著地改善和修复足细胞病变有关.     

实验性慢性肾缺血模型肾小管-间质细胞a-平滑肌肌动蛋白的表达和意义

目的:观察单侧肾动脉狭窄(RAS)大鼠模型慢性肾缺血组织中肾小管-间质a-平滑肌肌动蛋白(a-SMA)的表达和意义。 方法:建立Goldblatt单侧RAS大鼠模型,观察大鼠慢性缺血肾脏在90天内不同阶段的病理改变;应用免疫组化法检测肾小管-间质a-SMA及波形蛋白(vimentin)在不同时间点的表达;应用免疫荧光双标记激光共聚焦显微镜观察细胞角蛋白(cytokeratin,CK)与a-SMA在肾小管上皮细胞中的共定位情况。 结果:RAS术后第5天首先出现肾小管vimentin阳性,术后第7天肾间质可见少量的a-SMA阳性细胞并随时间递增。通过连续切片观察到,vimentin阳性的肾小管周围肾间质细胞a-SMA表达增强,并与肾小管间质纤维化程度基本一致。当慢性缺血状态持续存在时,后期(术后第45天至90天)少数损伤的肾小管上皮细胞表达a-SMA。应用免疫荧光双标记激光共聚焦显微镜观察发现,部分a-SMA阳性的肾小管上皮细胞同时表达CK,并且个别细胞还有向间质游走的趋势。 结论:在慢性肾缺血早期Vimentin阳性的肾小管上皮细胞本身可能诱导了肾间质固有细胞发生肌成纤维细胞转分化,参与肾间质纤维化的发生和发展;在慢性肾缺血后期,肾小管上皮细胞转分化可能是导致肾纤维化进行性发展的关键环节。     

百令及其提取液对大鼠环孢素A肾毒性的防治作用

目的 :观察百令及其提取液对环孢素A(CsA)肾毒性的防治作用。　 方法 :以 2 5mg/ (kg·d)剂量的CsA皮下注射制作大鼠CsA肾毒模型 ,同时以 1 5g/ (kg·d)剂量的百令或相当剂量的提取液喂饲以预防肾毒性 ,分别于治疗 1周、2周和 4周时作有关指标的测定。　 结果 :本实验成功地制作出了大鼠CsA肾毒模型 ,模拟出了CsA肾中毒的典型功能学和形态学改变。百令及其提取液能明显改善CsA肾中毒大鼠的肾小管损害 ,防止尿量增多、减少尿N 乙酰 β 氨基葡萄糖苷酶和尿钠的排泄、改善尿低渗透压状态 ,也防止CsA用药后引起的血清肌酐升高。它们明显降低血胆固醇水平 ,但对血三酰甘油有升高作用。组织形态学证实 ,百令及其提取液能减少肾小管上皮细胞空泡变性和细胞坏死 ,减少间质炎细胞浸润及间质纤维化 ,降低小血管的透明样变性的发生率 ;同时也抑制转化生长因子 β在小血管的表达 ,减少纤维连接蛋白在球囊壁和血管的沉积。　 结论 :百令及其提取液能有效地防治CsA肾毒性     

实验性慢性肾缺血模型肾小管-间质细胞α-平滑肌肌动蛋白的表达和意义

目的：观察单侧肾动脉狭窄(RAS)大鼠模型慢性肾缺血组织中肾小管-间质α-平滑肌肌动蛋白(α-SMA)的表达和意义。方法：建立Goldblatt，单侧RAS大鼠模型，观察大鼠慢性缺血肾脏在90天内不同阶段的病理改变；应用免疫组化法检测肾小管-间质α-SMA及波形蛋白(vimentin)在不同时间点的表达：应用免疫荧光双标记激光共聚焦显微镜观察细胞角蛋白(cytokeratin，CK)与α-SMA在肾小管上皮细胞中的共定位情况。结果：RAS术后第5天首先出现肾小管vimentin阳性，术后第7天肾间质可见少量的α-SMA阳性细胞并随时间递增。通过连续切片观察到，vimentin阳性的肾小管周围肾间质细胞α-SMA表达增强，并与肾小管间质纤维化程度基本一致。当慢性缺血状态持续存在时，后期(术后第45天至90天)少数损伤的肾小管上皮细胞表达α-SMA。应用免疫荧光双标记激光共聚焦显微镜观察发现，部分α-SMA阳性的肾小管上皮细胞同时表达CK，并且个别细胞还有向间质游走的趋势。结论：在慢性肾缺血早期Vimentin阳性的。肾小管上皮细胞本身叮能诱导了肾间质固有细胞发生肌成纤维细胞转分化，参与肾间质纤维化的发生和发展；在慢性肾缺血后期，肾小管上皮细胞转分化可能是导致肾纤维化进行性发展的关键环节。     

雷公藤对大鼠肾移植急性排异反应治疗作用的免疫机理探讨

利用大鼠肾移植模型,以血、尿及移植肾组织免疫活性细胞、白细胞介素为研究指标,探讨GTW抗大鼠急性排异作用机理。结果量示,GTW可抑制移植肾组织排异反应。可减少肾移植大鼠外周血MRC OX-8阳性细胞(Tc/s,NK细胞)数量,抑制W3/2S(Th,单核细胞)、MRCOX-8(Ts/c,NK细胞)、MRCOX-19(T细胞)和IL-2R阳性细胞在移植肾组织内的浸润,减少尿IL-6的产生.斑点杂交未证实GTW可抑制移植肾组织IL-1α,βmRNA的表达.     

细胞凋亡和细胞自噬在慢性环孢素A肾毒性中的作用

目的探讨细胞凋亡和细胞自噬在慢性环孢素A(CsA)肾毒性中的作用。方法 Sprague-Dawley大鼠分为两组:对照组:皮下注射橄榄油(1 ml·kg-1·d-1)4 w;慢性CsA肾毒性组:皮下注射CsA(15 mg·kg-1·d-1)4 w。检测两组大鼠的体重和肾功能;三色染色检测肾小管间质纤维化程度;ELISA法检测血、尿8羟基脱氧鸟苷(8-OHdG)水平;原位末端标记法(TUNEL)染色观察细胞凋亡;免疫印迹法检测细胞凋亡调控基因(Bcl-2、Bax、Caspase-3)和细胞自噬体膜型LC3-Ⅱ蛋白的表达;Pearson直线相关分析肾小管间质纤维化程度与细胞凋亡和LC3-Ⅱ蛋白表达的相关关系。结果与对照组相比,毒性组大鼠体重减轻、肾功能低下、血尿8-OHdG水平升高,同时肾毒性组可见明显的肾小管间质纤维化和大量TUNEL阳性细胞。免疫印迹结果表明,毒性组Bax、Caspase-3、LC3-Ⅱ蛋白的表达明显增加,反之,Bcl-2的表达显著减少。直线相关分析提示,肾小管间质纤维化程度与TUNEL阳性细胞数和LC3-Ⅱ蛋白表达呈正向相关。结论细胞凋亡和细胞自噬参与了慢性CsA肾毒性肾小管间质的损伤。     

雷公藤甲素对嘌呤霉素模型足细胞病变的影响

目的：研究雷公藤甲素对非免疫因素介导的、单纯足细胞病变模型——嘌呤霉素氨基核苷（PAN）肾病模型的疗效及其对足细胞病变的影响。方法：采用PAN单次颈静脉注射法建立PAN肾病模型。大鼠分为正常对照组，模型组，雷公藤甲素预防组和治疗组。分别在1天、3天、5天、10天、14天和21天收集血尿标本，并处死大鼠留取肾组织标本。检测24h尿蛋白排泄量、血生化指标，行肾组织光镜和电镜观察肾小球病变和足突超微结构。采用定量学方法测定足突宽度。免疫荧光染色观察足细胞裂孔膜分子Nephrin和Podocin表达和分布变化。结果：雷公藤甲素无论是预防还是治疗性用药均能明显改善PAN肾病大鼠的肾病综合征状况，明显减少尿蛋白，加快血清白蛋白回升和血脂水平恢复。与此同时，雷公藤甲素预防组和治疗组大鼠在各观察点足突融合程度和范围均比PAN肾病大鼠明显减轻，至第14天仅见少数足突融合，第21天足突形态已基本恢复正常。雷公藤甲素预防性和治疗性用药均能够增加足细胞裂孔膜分子Nephrin和Podocin表达，促进其分布异常的修复。在第10天，Nephrin和Podocin不仅表达较PAN肾病大鼠明显增多，而且大部分血管袢已开始呈现连续的线状分布，以Podocin更为明显；两者的表达和分布在第14天已基本恢复，至第21天已完全恢复正常。结论：雷公藤甲素对PAN导致的足细胞损伤模型具有明显的预防和治疗作用，表现为减少蛋白尿，改善足突融合，恢复足细胞相关蛋白的表达及其分布，逆转足细胞病变。     

肾脏HLA-DR抗原表达在肾移植中的意义

应用免疫酶标技术对47例异体肾移植患者的95例次肾活检标本进行HLA-DR抗原的检测,并同时做光镜、电镜、免疫病理检查及淋巴细胞亚群的研究。结果显示:肾移植后近曲小管上皮细胞的DR抗原表达增加,肾小球的DR抗原表达减少;急、慢性排导反应,急性肾小管坏死时,肾小管及肾间质的DR抗原表达均明显增加;环孢素中毒时,肾单位的DR抗原表达正常,肾间质的DR抗原表达增加。肾脏HLA-DR抗原表达在肾移植后的变化,对于排异反应的诊断、鉴别诊断、判断预后及治疗决策具有重要意义。     

雷公藤多苷纳米乳在大鼠肾移植中的免疫抑制作用

目的制作雷公藤提取物新剂型,提高生物利用度,尝试开发有品质的免疫抑制剂。方法利用自制雷公藤多苷纳米乳(NanoTII),腹腔内或口服给药途径作用于实验用大鼠肾移植模型。Wistar大鼠为供体,SD大鼠为受体行大鼠原位肾移植术。空白对照组:给予口服安慰剂;对照组:给予口服环孢素(Cs A);实验对照组:给予常规的雷公藤提取物片剂(TII);实验组:给予新型纳米雷公藤提取物胶囊;手术对照组:SD大鼠近交系原位肾移植,给予口服安慰剂。检测肾移植术后大鼠尿量、肾功、肝功、急性排斥反应发生率、移植肾/受体存活率。结果实验组大鼠移植肾生存期为(86±12.2)d;生存分析log-rank检验结果认为新型纳米乳雷公藤药物组的大鼠生存期显著长于传统雷公藤给药组(P0.01),但与标准对照组相比没有统计学意义(P=0.124)。药物毒性大小排序为:TIINano-TIICs A。结论在大鼠肾移植模型中,移植术后单独应用雷公藤多苷纳米乳相比传统TII具有更好的移植物存活率和更小的药物毒性,此项工作为纳米技术雷公藤新剂型的临床应用提供了实验依据。     

丹参酮ⅡA对大鼠肾间质纤维化的抑制作用

目的：探讨丹参酮ⅡA对大鼠肾间质纤维化的作用及机制。方法：30只雄性SD大鼠随机分为假手术组、模型组和丹参酮ⅡA组。结扎大鼠单侧输尿管建立肾间质纤维化动物模型。丹参酮ⅡA经腹腔注射，剂量为1．5mg／（kg·d）。术后第10天取梗阻侧肾组织作HE、Masson染色，观察肾间质病理改变。免疫组化法检测肾组织转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）及Ⅰ型胶原的蛋白表达与定位。逆转录-聚合酶链反应（RT-PCR）检测三者的mRNA水平。结果：模型组术后第10天梗阻侧出现明显的肾间质纤维化，肾组织TGF-β1、α—SMA和Ⅰ型胶原的蛋白及mRNA表达显著增加（P〈0．01）。丹参酮ⅡA组肾间质纤维化程度减轻，肾组织TGF-β1、α—sMA及Ⅰ型胶原表达下调（P〈0．05）。结论：丹参酮ⅡA对大鼠肾间质纤维化有明显的抑制作用，其机制可能与下调TGF-β1表达，抑制成纤维细胞增殖和表型转化，减少胶原沉积有关。     

Mycophenolate Mofetil Reduces Renal Injury in the Chronic Nitric Oxide Synthase Inhibition Model

-We and others have recently shown that mycophenolate mofetil (MMF) reduces renal inflammation and glomerular and interstitial injury in the 5/6 renal ablation model. In the present study, we investigated whether MMF limits renal injury in a model of chronic nitric oxide (NO) inhibition associated with a high-salt diet and characterized by progressive systemic hypertension, albuminuria, glomerular sclerosis and ischemia, interstitial expansion, and progressive macrophage infiltration. Adult male Münich-Wistar rats were distributed among 3 groups: HS, rats receiving a high-salt diet (3.2% Na); HS+N, HS rats orally treated with the NO inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME), 25 mg. kg(-1). d(-1); and HS+N+MMF, HS+N rats orally treated with MMF, 10 mg. kg(-1). d(-1). Renal hemodynamics were studied after 15 days of treatment; histological and immunohistochemical studies were conducted after 30 days of treatment. MMF treatment did not reverse the hemodynamic alterations characteristic of this model. Renal injury in the HS+N group was associated with macrophage and lymphocyte infiltration. Treatment with MMF reduced glomerular and interstitial injury and limited macrophage and lymphocyte infiltration. These results suggest that renal inflammation is a strong independent factor in the pathogenesis of the nephropathy associated with the HS+N model.     

Selective inhibition of the renal angiotensin type 2 receptor increases blood pressure in conscious rats

The angiotensin II type 2 (AT(2)) receptor is present in rat kidney; however, its function is not well understood. The purpose of this study was to evaluate the role of the AT(2) receptor in blood pressure (BP) regulation. The effects of selective inhibition of the renal AT(2) receptor with phosphorothioated antisense oligodeoxynucleotide (AS-ODN) were examined in conscious uninephrectomized rats. Oligodeoxynucleotides (AS-ODN or scrambled [S-ODN]) were infused directly into the renal interstitial space by using an osmotic pump at 1 microL/h for 7 days. Texas red-labeled AS-ODN was distributed in renal tubules in the infused but not the contralateral kidney of normal rats. Continuous renal interstitial infusion of the AS-ODN, but not S-ODN, caused a significant (P<0.01) increase in BP 1 to 5 days after the initiation of the infusion. AS-ODN-treated rats experienced an increase in systolic BP from 109+/-4 to 130+/-4 mm Hg (n=8, P<0.01), whereas S-ODN-treated (n=8) and vehicle-treated (n=8) rats did not show any significant change in BP. On day 5 of the oligodeoxynucleotide infusion, AS-ODN-treated rats exhibited a greater pressor response to systemic angiotensin II infusion (30 ng/kg per hour) than did S-ODN-treated rats (P<0.01). Renal interstitial fluid cGMP decreased from 11.9+/-0.8 to 3.6+/-0.5 pmol/mL (P<0.001), and bradykinin decreased from 0.05+/-0.05 to 0.18+/-0.03 ng/mL (P<0.001) in response to AS-ODN, but they were not significantly changed in response to S-ODN. To evaluate the effects of AS-ODN and S-ODN on AT(2) receptor expression, Western Blot analysis was performed on treated kidneys. Kidneys treated with AS-ODN had approximately 40% less expression of AT(2) receptor than did kidneys treated with S-ODN or vehicle (P<0.05). These results suggest that AS-ODN directed selectively against the renal AT(2) receptor decreased receptor expression and caused an increase in BP. We conclude that the renal AT(2) receptor plays an important role in the regulation of BP via a bradykinin/cGMP vasodilator signaling cascade.     

Normalization of pressure-natriuresis by nisoldipine in spontaneously hypertensive rats.

This study examined whether the calcium antagonist nisoldipine can shift the relations between sodium excretion, papillary blood flow, renal interstitial pressure, and renal perfusion pressure toward lower pressures in spontaneously hypertensive rats. Mean arterial pressure decreased similarly by 9% and 12% in Wistar-Kyoto and spontaneously hypertensive rats after nisoldipine (0.5 microgram/kg bolus + 0.017 microgram/kg/min). Urine flow and sodium excretion increased by 35% and 24% in Wistar-Kyoto rats after nisoldipine. In contrast, urine flow and sodium excretion rose by 121% and 132% in spontaneously hypertensive rats, and fractional sodium excretion rose from 1.9 +/- 0.3 to 4.2 +/- 0.4%. Control sodium excretion, papillary blood flow, and renal interstitial pressure were significantly lower in spontaneously hypertensive rats than in Wistar-Kyoto rats when compared at similar renal perfusion pressures. Sodium excretion, papillary blood flow, and renal interstitial pressure all increased in spontaneously hypertensive rats after nisoldipine, whereas it had no effect on papillary blood flow or renal interstitial pressure in Wistar-Kyoto rats. The relations among sodium excretion, papillary blood flow, renal interstitial pressure, and renal perfusion pressure were shifted toward lower pressures in spontaneously hypertensive rats given nisoldipine and became similar to those seen in Wistar-Kyoto rats. These results indicate that nisoldipine normalizes the relations among sodium excretion, renal interstitial pressure, papillary blood flow, and renal perfusion pressure in spontaneously hypertensive rats perhaps by correcting the defect in renal medullary perfusion associated with resetting of pressure natriuresis in this model of hypertension.     

Role of prostaglandins in proximal tubule sodium reabsorption: response to elevated renal interstitial hydrostatic pressure

Previous studies have shown that the elevation of renal interstitial hydrostatic pressure by the direct expansion of renal interstitial volume increases urinary sodium excretion. The objective of the present study was to investigate whether proximal tubules respond to the elevated renal interstitial hydrostatic pressure and whether the inhibition of prostaglandin synthesis would alter the effect of elevated renal interstitial hydrostatic pressure on proximal sodium reabsorption. Expansion of renal interstitial volume by injecting 100 microliters of 2.5% albumin solution through a chronically implanted matrix increased renal interstitial hydrostatic pressure similarly in control rats (n = 8) and in indomethacin (n = 8) or meclofenamate-treated (n = 7) rats. In the absence of prostaglandin synthesis inhibition, renal interstitial volume expansion significantly increased the fractional delivery of sodium at the superficial late proximal tubules from 56.5 +/- 6.1 to 67.0 +/- 6.5% (p less than 0.01) with an accompanying increase in fractional excretion of sodium from 2.1 +/- 0.5 to 3.0 +/- 0.4% (p less than 0.01). In the presence of indomethacin or meclofenamate, renal interstitial volume expansion failed to augment the fractional delivery of sodium and the fractional excretion of sodium. In summary, these studies demonstrate that the synthesis of prostaglandins plays a role in the regulation of sodium reabsorption by the proximal tubules in response to elevated renal interstitial hydrostatic pressure.     

Intrarenal angiotensin II is associated with inflammation,renal damage,and dysfunction in Dahl salt-sensitive hypertension

The goal of this study was to test the hypothesis that intrarenal angiotensin (Ang) II has a proinflammatory effect leading to renal damage and dysfunction in Dahl salt-sensitive (S) rats on high-Na intake. Forty-six 7- to 8-week old Dahl S or Dahl salt-resistant (R)/Rapp strain rats were maintained for 5 weeks on high sodium (8%) with or without candesartan cilexetil in daily doses of 10 to 15 mg/kg/day. Arterial catheters were implanted at day 28. By day 35 in the high-Na S + candesartan rats, renal tissue Ang II concentration, renal monocytes/macrophages, tumor necrosis factor-α, and monocyte chemoattractant protein-1 significantly decreased. Plasma Ang II remained at very low levels in all groups. Reduced renal damage in candesartan-treated Dahl S rats was demonstrated by marked decreases in urinary protein excretion and renal glomerular and interstitial damage. After 5 weeks of high-Na, compared with high-Na Dahl S rats, arterial pressure was unchanged in candesartan S rats, but creatinine clearance was increased. Therefore, candesartan reduced renal tissue Ang II, renal damage, infiltration of immune cells, cytokines, chemokines, and improved renal hemodynamics. These data suggest that intrarenal Ang II plays an important role in causing renal inflammation, which leads to renal cortical damage, proteinuria, and decreases in renal hemodynamics.     

Two cases of pulmonary disease with perinuclear anti-neutrophil cytoplasmic antibody]

We encountered two cases of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA). The first was a case of idiopathic interstitial pneumonia diagnosed in a 73-year-old man since 1998. He was admitted to our hospital because of renal failure and anemia. The serum level of p-ANCA on admission was 264 EU, and specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis due to p-ANCA. He was treated with prednisolone pulse therapy and prednisolone (PSL), however interstitial pneumonia occurred during PSL tapering. We treated him for pulmonary fibrosis with plasmapheresis, methylprednisolone (mPSL) and cyclophosphamide (CPA), which suppressed the progress of the interstitial pneumonia. The second case was one of massive pulmonary hemorrhage in a 68-year-old man who was admitted to our hospital. Physical examination revealed anemia: the laboratory data, renal failure; and the serum level of p-ANCA was elevated to 611 EU. The specimens obtained by percutaneous renal biopsy showed crescentic glomerulonephritis and vasculitis. The renal failure was not improved by PSL, but, together with the inflammation, responded to the combination of PSL and CPA. However, both patients died of serious infection. They were regarded as compromised patients because of the therapy mentioned above. No standard therapy has been established against p-ANCA positive pulmonary disease with renal failure. The treatment should control the progression of interstitial pneumonitis and pulmonary hemorrhage. It is important to consider the possibility of serious infection.     

Renal protective effects of blocking the intrarenal renin-angiotensin system: angiotensin II type I receptor antagonist compared with angiotensin-converting enzyme inhibitor.

The present study compared renoprotective effects of angiotensin II type I receptor antagonist (AT1RA) with angiotensin converting enzyme inhibitor (ACEI), and their influence on the renin-angiotensin-system (RAS). Experimental nephrotic syndrome was induced in SD rats by repeated peritoneal injections of puromycin. Twenty-eight rats were randomly divided into four groups: normal control, nephrotic control, ACEI-treated, and AT1RA-treated groups. Serum, urine, and renal tissue were collected for study at the end of 12 weeks. Compared with those of the nephrotic control group, urinary protein was less and renal function was better in both treated groups. The glomerular and interstitial damage indexes of both ACEI- and AT1RA-treated rats were lower than those of nephrotic control rats, with no significant difference observed between the two treated groups. Local renal ACE activity and angiotensin II concentration were elevated in nephrotic rats (p< 0.01). However, there is no significant difference in circulating RAS, renal tissue renin, and aldosterone between the normal control and nephrotic control rats. As expected, enalapril inhibited the local renal ACE activity and significantly decreased angiotensin II (p< 0.01). Intrarenal ACE activity and angiotensin concentration returned to normal levels after treatment with irbesartan (p< 0.01). In conclusion, AT1RA and ACEI have comparable renal protective effects, and these protective effects were associated with the inhibition of intrarenal ANG II.