普罗布考防治大鼠顺铂急性肾损伤的实验研究

目的：复制大鼠顺铂急性肾损伤模型,研究氧化应激与核转录因子Sp1及凋亡的关系;探讨普罗布考对顺铂急性肾损伤的保护作用及作用机制。方法：24只SD雄性大鼠被随机分为生理盐水对照组、顺铂模型组、普罗布考干预组、普罗布考对照组,每组6只;检测尿N-乙酰-β-D-氨基葡萄糖甘酶（NAG）、血清肌酐（Scr）、血尿素氮（BUN）、肾组织匀浆液丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）,光镜观察肾脏病理改变;采用免疫组化染色检测肾组织Sp1蛋白表达;采用TUNEL染色检测肾小管上皮细胞凋亡。结果：与生理盐水对照组和普罗布考对照组相比,顺铂模型组大鼠血清BUN和Scr,尿NAG酶,肾脏组织匀浆MDA含量显著升高,肾组织匀浆GSH-Px活力显著下降（P〈0.01）;肾脏指数、肾小管损伤分数和肾小管上皮细胞凋亡百分比均明显增加（P〈0.01）;肾组织Sp1蛋白的表达上调。采用普罗布考干预后血清BUN和Scr,尿NAG酶,肾脏组织匀浆MDA含量显著下降（P〈0.05）;肾组织匀浆GSH-Px活力显著升高;肾脏指数、肾小管损伤分数和肾小管上皮细胞凋亡百分比均明显降低（P〈0.01）;肾组织Sp1蛋白的表达下调。结论：氧化应激和核转录因子Sp1在顺铂所致大鼠肾毒性中起一定作用;普罗布考对顺铂所致大鼠肾毒性有保护作用,其机制可能与抗氧化、抑制肾小管上皮细胞凋亡、下调肾组织Sp1蛋白表达有关。     

替普瑞酮对大鼠肾脏缺血再灌注损伤的保护作用

目的 探讨替普瑞酮对肾脏缺血再灌注损伤的保护作用和可能机制。 方法 应用替普瑞酮(400 mg/kg)诱导雄性SD大鼠肾脏高表达热休克蛋白72（HSP72）。以钳夹大鼠左肾蒂45 min后，松开血管夹并切除右肾，建立大鼠缺血再灌注肾脏损伤模型。假手术组为打开腹腔，分离肾血管周围组织，但不钳夹血管。模型建立后24 h处死大鼠，留取血清测血肌酐（Scr）和尿素氮（BUN）。肾组织石蜡切片行PAS染色，以损伤肾小管所占百分比评分法评估肾组织肾小管损伤程度。TUNEL法检测缺血再灌注损伤时肾脏细胞凋亡的发生情况。Western印迹检测X连锁凋亡抑制蛋白（XIAP）的水平。 结果 缺血再灌注损伤可导致急性肾衰竭，表现为血Scr、BUN明显升高（P < 0.01）；PAS染色显示外髓部有大片肾小管坏死，甚至出现基底膜裸露；TUNEL染色中肾小管上皮细胞TUNEL阳性细胞数明显增多（P < 0.01）；Western印迹结果显示，肾组织XIAP蛋白水平明显降低（P < 0.01）。替普瑞酮处理后，肾组织HSP72表达水平明显增高（P < 0.01）；缺血再灌注所致的肾脏损伤明显改善，包括肾小管的损伤、细胞凋亡以及肾功能。此外，替普瑞酮可稳定肾组织XIAP的蛋白水平（P < 0.05）。 结论 替普瑞酮可诱导肾脏高表达HSP72。替普瑞酮可能通过减少肾脏XIAP蛋白的降解，抑制细胞凋亡，减轻缺血再灌注的肾脏损伤。     

intermedin预处理对大鼠肾脏缺血再灌注损伤修复和再生过程的作用

目的 探讨intermedin （IMD）预处理对大鼠肾脏缺血再灌注（IR）损伤修复和再生过程的作用。 方法 将Wistar大鼠按随机数字表法分为4组：假手术组（sham）、IR组、转空质粒组和转IMD组。在切除右肾后,转IMD组用超声微泡造影剂介导的基因转染方法将IMD真核质粒转染到大鼠肾组织,用RT-PCR和Western印迹法检测转染效率。转染成功后,制作肾脏IR损伤模型,分别于再灌注后1 d、2 d、3 d、4 d、7 d和14 d 6个时间点各取6只大鼠,留取血清及肾组织标本,常规检测血清BUN和Scr;HE和PAS染色观察肾组织的病理变化;免疫组化法观察肾小管上皮细胞的增殖程度。 结果 （1）转IMD组比转空质粒组的IMD蛋白和mRNA表达均增多（均P < 0.05）,且转IMD组7 d时表达最多,与转IMD组4 d时差异无统计学意义;（2）与sham组相比,IR组1 d和2 d时Scr和BUN均显著增高（P < 0.05）;与IR组相比,转IMD组显著下降（P < 0.05）;转空质粒组与IR组相比差异无统计学意义（P > 0.05）。（3）IR组、转空质粒组和转IMD组大鼠的肾小管均受损,但转IMD组的损伤较轻,均以2 d时病理损伤最重。（4）sham组肾小管和肾小球内几乎没有增殖细胞核抗原（PCNA）阳性细胞的表达;IR组和转空质粒组的PCNA阳性数在IR损伤1 d时开始增加,7 d时最多;转IMD组的PCNA阳性细胞数在IR损伤1 d时开始增加,3 d时最多。与IR组1~4 d相比,转IMD组的PCNA阳性细胞数显著增加（P < 0.05）;与IR组7 d相比,转IMD组7 d的PCNA阳性细胞数显著减少（P < 0.05）。 结论 IMD预处理可以促进肾小管上皮细胞增殖,加速肾脏IR损伤修复和再生。     

祛毒颗粒对单侧输尿管梗阻大鼠肾间质纤维化的干预作用

目的：观察祛毒颗粒对单侧输尿管梗阻（unilateral ureteral obstruction,UUO）大鼠肾间质纤维化的干预作用,并探讨其作用机制。方法：将90只雄性Wistar大鼠随机分为5组：假手术组、模型组、尿毒清组（对照组）、祛毒颗粒低剂量组（低剂量组）、祛毒颗粒高剂量组（高剂量组）,每组18只,除假手术组,其余各组用单侧输尿管梗阻法（UUO）建立肾间质纤维化动物模型,术前1天起各组给予相应浓度和剂量的药物,分别在术后第3天、7天、14天分批处死大鼠,检测大鼠尿N-已酰-β-氨基葡萄糖苷（NAG）酶、血肌酐（Scr）和尿素氮（BUN）变化,梗阻侧肾组织行HE染色和Masson染色,HE染色观察肾组织病理变化并半定量计算肾小管损伤指数（tubulointerstitial injuryindex,TII）,Masson染色测定肾间质胶原面积,免疫组化法检测结缔组织生长因子（CTGF）、Ⅰ型胶原（ColⅠ）、肝细胞生长因子（HGF）、骨形成蛋白（BMP）-7在肾组织的表达。结果：与模型组及对照组相比,祛毒颗粒能明显降低UUO大鼠术后14d的尿NAG酶、Scr、BUN（P〈0.05）;对梗阻侧肾组织HE染色进行TII评分发现,不同时间点,2个试验组大鼠肾小管损伤指数低于模型组和对照组（P〈0.05～0.01）;Masson染色测定肾间质胶原面积,2个实验组大鼠肾间质胶原面积少于模型组和对照组（P〈0.05～0.01）;免疫组化法染色发现,与模型组和对照组相比,2个试验组大鼠CTGF、ColⅠ在肾组织的表达下调（P〈0.05）,HGF、BMP-7在肾脏组织的表达上调（P〈0.05）。结论：祛毒颗粒具有改善肾间质纤维化的作用,其机制可能与下调UUO大鼠致纤维化因子CTGF、ColⅠ在肾脏的表达,上调抗纤维化因子HGF、BMP-7在肾脏的表达有关。     

α促黑素细胞激素对横纹肌溶解所致急性肾衰竭大鼠肾的保护作用

目的探讨α促黑素细胞激素（α—MSH）是否能减轻甘油诱导横纹肌溶解所致急性。肾衰竭（ARF）大鼠。肾组织中炎性反应和对。肾损害的保护作用。方法48只SD大鼠随机分4组：健康对照组：肌注生理盐水10ml／kg；ARF组;肌注50％甘油10ml／kg；α-MSH立即干预组：肌注50％甘油的同时腹腔注射α—MSH200μg／kg，12h后重复1次；α-MSH延迟干预组：肌注50％甘油6h后腹腔注射α—MSH200μg／kg，12h后重复1次。24h后处死大鼠，测Scr、BUN、肌酸激酶水平。。肾组织PAS染色光镜下行。肾小管坏死半定量评分。免疫组化ED-1染色半定量计数。实时定量PCR测。肾组织中单核细胞趋化因子（MCP）-1mRNA表达水平。结果与对照组相比，ARF组大鼠。肾组织内ED．1染色阳性细胞数（16．8±7．0比1．46＋1．24）、MCP-1的mRNA表达量（11．0±3．8比7．8±1．9）均显著增加（P均〈0．05）。α-MSH立即干预组ED-1染色阳性细胞数（9．5±8．2）和MCP．1的mRNA表达量（8．7±5．1）与ARF组相比均显著减少（P〈0．05）。α—MSH立即干预组Scr、BUN和。肾小管坏死评分均低于ARF组【分别为（152±76）比（333±60）μmol／L、（23．8±9．3）比（56．0±10．0）mmol／L和1．7±0．4比2．7±0．4，P均〈0．05]。而α-MSH延迟干预组与ARF组间各指标及各组间血IL．6和TNF—α差异均无统计学意义。结论甘油所致急性。肾衰竭大鼠。肾组织中巨噬细胞浸润及MCP-1表达增加，即刻注射α-MSH有一定的抑制。肾组织炎性反应、减轻。肾损害作用。     

ApoE-/-小鼠肾动脉粥样硬化斑块破裂的肾损害

目的 探讨ApoE^-/-小鼠肾动脉粥样硬化斑块破裂对下游肾脏的损伤机制。 方法 采用ApoE^-/-小鼠建立粥样硬化性肾动脉狭窄(ARAS)动物模型。选择肾动脉狭窄程度 <50％的ApoE^-/-小鼠，按斑块分为破裂组和未破裂组；选择同条件喂养的C57BL/6J 野生型小鼠为对照组。常规检测Scr及尿 N-乙酰-β-氨基葡萄糖苷酶(NAG)活性；Western印迹检测细胞核中核转录因子κBp65（NF-κBp65）、细胞间黏附分子1（ICAM-1）及P-选择素（P-sel）表达； RT-PCR检测白细胞介素6 （IL-6）mRNA表达；免疫组化染色检测巨噬细胞浸润情况。 结果破裂组Scr和尿NAG活性明显升高（均P < 0.01）；肾组织出现病理改变，肾间质中巨噬细胞浸润增加（P < 0.05）；细胞核中NF-κBp65表达增加（P < 0.05）；ICAM-1、P-sel、IL-6 mRNA表达增加（P < 0.05）。未破裂组上述指标与对照组比较，差异无统计学意义（P > 0.05）；肾脏未见明显病理改变。 结论 肾动脉粥样硬化斑块破裂可引起肾脏病理改变和肾功能受损；在粥样硬化性肾动脉狭窄的肾损害机制中，炎性反应是重要因素之一。     

番茄红素对糖尿病大鼠造影剂肾病的保护作用

目的：探讨番茄红素对糖尿病大鼠造影剂肾病的预防作用.方法：建立单侧肾切除糖尿病大鼠模型,模型建立8周后分4组：正常对照组（SD组）,糖尿病对照组（DM组）,糖尿病＋造影剂组（CM组）和糖尿病＋番茄红素＋造影剂组（LP组）,其中CM组尾静脉内1次性注入76%泛影葡胺（3 gI/kg）,LP组在注射造影剂前一天和后两天均予以番茄红素20 mg/kg灌胃,每12 h 1次,共6次.注射造影剂72 h后测定血清尿素氮（BUN）、血肌酐（Scr）、血糖水平和尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）活性;测定肾皮质组织中丙二醛（MDA）水平、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性;HE染色观察肾脏病理改变.结果：与SD组相比,DM组大鼠BUN、Scr和肾组织MDA水平显著增加,肾组织SOD和CAT活性降低.与DM组相比,CM组BUN、Scr和肾组织MDA水平进一步增加,肾组织SOD和CAT活性进一步降低,尿NAG含量明显升高,肾脏病理改变明显.给予番茄红素预防使用后（LP组）明显减轻上述改变.结论：番茄红素可能通过抗氧化应激作用减轻造影剂泛影葡胺对糖尿病大鼠的肾毒性.     

X线造影剂对高胆固醇血症大鼠的肾毒性及己酮可可碱的保护作用

目的 比较不同渗透浓度X线造影剂对高胆固醇血症大鼠的肾毒性，探讨己酮可可碱（PTX）对造影剂肾毒性是否有保护作用。 方法 48只健康雄性SD大鼠，随机分为正常饮食组8只（NN组）和高胆固醇饮食组40只（H组，4%胆固醇+1%胆酸钠）。8周末，高胆固醇饮食组随机分为5组，每组8只，分别为高胆固醇饮食组（HN组）、高胆固醇+低渗造影剂组（HL组）、高胆固醇+等渗造影剂组（HI组）、高胆固醇饮食+高渗造影剂组（HH组）、高胆固醇+高渗造影剂+PTX组（HHP组）。在注射造影剂后48 h测定各组大鼠的血清总胆固醇、三酰甘油、血清肌酐、内生肌酐清除率（Ccr）、钠钾排泄分数及血管紧张素Ⅱ（AngⅡ）的浓度；光镜下观察肾组织学改变；免疫组化法检测肾组织NF-κB的蛋白表达；原位细胞调亡（TUNEL）染色检测肾小管上皮细胞的凋亡。 结果 所有给予高胆固醇饮食的大鼠血清总胆固醇水平明显增高（P < 0.05）。HH组的血清肌酐、钠钾排泄分数及血浆Ang Ⅱ水平均分别明显高于HHP组、HL组及HI组（P < 0.05）；HH组Ccr水平[（0.11±0.02） ml·min-1·（100 g）-1]则明显低于HHP组[（0.43±0.03） ml·min-1·（100 g）-1]、HL组[（0.25±0.02） ml·min-1·（100 g）-1]和HI组[（0.27±0.03） ml·min-1·（100 g）-1]（P < 0.05）。组织病理显示，HH组大鼠肾小管上皮细胞发生明显的变性和坏死，肾小管上皮细胞凋亡率（89.60%±6.40%）明显高于其他各组[NN组（2.40％±0.77％）、HN组（5.60％±1.08％）、HHP组（8.91％±1.44％）、HL组（63.34％±11.97％）、HI组（61.50％±9.40％）]（P < 0.05）。肾组织NF-κB阳性细胞的平均灰度值明显低于其他各组（P < 0.05）；而HL组和HI组间上述指标比较差异无统计学意义 （P > 0.05）。 结论 高胆固醇血症环境下注射不同渗透浓度X线造影剂均可致造影剂肾损害。PTX对高胆固醇血症环境下所致的造影剂肾毒性有保护作用。     

动员自体骨髓干细胞对大鼠急性肾小管坏死的治疗

目的：观察粒细胞集落刺激因子联合干细胞因子动员骨髓干细胞的作用、骨髓干细胞是否具有向损伤肾组织归巢的能力及其在肾脏组织中的分布,初步探讨粒细胞集落刺激因子联合干细胞因子是否具有促进急性肾小管坏死修复的作用。方法：160只8～10周龄雄性SD大鼠随机分为4组：对照组,模型组、G-CSF＋SCF治疗组、G-CSF＋SCF对照组,检测：（1）外周血白细胞总数及单个核细胞中CD34＋细胞百分比的变化;（2）尿NAG酶检测;（3）肾脏组织病理学改变;（4）肾组织CD34＋细胞表达变化。结果：（1）G-CSF＋SCF治疗组和G-CSF＋SCF对照组外周血中白细胞数、CD34＋细胞百分比于第5天达高峰,与对照组、模型组相比,差异有统计学意义（P〈0.05）,以后逐渐下降;相应地,G-CSF＋SCF治疗组肾组织内CD34＋细胞较对照组、模型组也明显增多（P〈0.05）。（2）手术后第5、10、17天,G-CSF＋SCF治疗组尿NAG酶、肾脏病理学改变均明显好于模型组（P〈0.05）。第24天G-CSF＋SCF治疗组尿NAG酶、肾脏病理学改变基本恢复正常,而模型组仍异常。第31天各组间尿NAG酶、肾脏病理学改变其差异无统计学意义。结论：（1）粒细胞集落刺激因子和干细胞因子联合应用对缺血再灌注损伤诱发急性肾小管坏死大鼠的骨髓干细胞有显著的动员作用。（2）骨髓干细胞能在损伤的肾小管归巢和定居,并可能参与损伤肾组织的修复。（3）粒细胞集落刺激因子和干细胞因子联合应用能在一定程度上加速急性肾小管坏死后肾功能的修复。     

抗纤灵二号方对单侧输尿管梗阻大鼠肾小管上皮细胞转分化的调节作用

目的：通过研究中药复方——抗纤灵二号方对单侧输尿管梗阻（unilateral ureteral obstruction,UUO）大鼠肾间质α-平滑肌肌动蛋白（alpha-smooth muscle actin,α-SMA）、转化生长因子-β1（transforming growth factor-beta1,TGF-β1）、肝细胞生长因子（hepatocyte growth factor,HGF）表达的影响,探讨其对肾小管上皮细胞间充质转分化（epithelial mesenchymal transdifferentiation,EMT）的调节机制。方法：建立大鼠UUO模型,90只SD大鼠随机分为假手术组、模型组、代文组,及抗纤灵二号方低、中、高剂量组,于造模4周后腹主动脉采血检测血清肌酐（serum creatinine,Scr）、尿素氮（blood urea nitrogen,BUN）,收集24h尿液检测N-乙酰-β-D-氨基葡萄糖苷酶（N-acetyl-β-D-glucosaminidase,NAG）、β2-微球蛋白（β2-mi-croglobulin,β2-MG）,取梗阻侧肾组织,HE、Masson染色观察肾小管间质病变,免疫组织化学染色观察α-SMA、TGF-β1及HGF在肾间质的阳性染色表达,免疫印迹法检测肾组织α-SMA的蛋白表达,并进行半定量分析。结果：与假手术组相比,模型组大鼠Scr、BUN、尿NAG、β2-MG水平以及α-SMA、TGF-β1阳性表达显著升高（P〈0.01）。与模型组相比,抗纤灵二号方高剂量组大鼠Scr、BUN水平降低,尿NAG、β2-MG排泄减少（P〈0.01）;抗纤灵二号方高剂量组和代文组α-SMA、TGF-β1阳性表达显著下调,而HGF阳性表达则显著上调（P〈0.01）,α-SMA蛋白表达也明显下调（P〈0.05）;低、中、高三个剂量组的疗效呈剂量依赖关系。结论：抗纤灵二号方可能通过改善肾小球、肾小管功能,抑制α-SMA、TGF-β1的表达,诱导HGF的高表达,从而抑制肾小管EMT,达到改善肾间质纤维化的作用。     

Expression of Augmenter of Liver Regeneration in Rats with Gentamicin-Induced Acute Renal Failure and Its Protective Effect on Kidney

Augmenter of liver regeneration (ALR) enhances the proliferation of hepatocytes and accelerates recovery from acute liver failure in animal models. ALR is expressed in both the liver and kidney; however, the specific location of ALR expression and its biological effects in the kidney remain unknown. We aimed to investigate the efficacy of ALR in rats with gentamicin (GM)-induced acute renal failure (ARF). Rats were randomized into the normal group, GM+saline group, GM+vehicle group, and GM+rrALR group. Blood urea nitrogen, serum creatinine, and urine beta-N-acetyl-D-glucosaminidase were measured, and histological analyses of the kidneys were performed. The expression of ALR protein was determined by immunohistochemistry and Western blotting. In vitro incorporation of tritiated thymidine was used to measure the proliferation of renal tubular epithelial cells. In normal rats, the expression of ALR protein was faint in the medulla and absent in the cortex. However, in ARF rats, ALR expression increased significantly in both the renal cortex and medulla. Histological analyses revealed that treatment with recombinant rat ALR (rrALR) reduced the extent of injury of tubular cells in the renal cortex. Serum/urine biochemical parameters also showed that renal dysfunction was improved by the administration of rrALR. Intraperitoneal injection of rrALR enhanced the proliferation of tubular cells in vivo. We also confirmed that rrALR could promote the proliferation of renal tubular cells in vitro. These results indicate that rrALR effectively accelerates kidney recovery after ARF induced by gentamicin, and that the protective effect is associated with enhanced proliferation of renal tubular cells.     

卡维地洛改善顺铂致肾小管上皮细胞凋亡

目的 观察顺铂致急性肾衰竭(ARF)中肾小管上皮细胞凋亡情况及卡维地洛(carvedilol)对其影响,并探讨其作用机制。方法 雄性Wistar大鼠随机分为盐水对照组、顺铂组、卡维地洛对照组、卡维地洛治疗组。测定BUN、Scr、尿乙酰氨基葡糖苷酶(NAG)、肾组织丙二醛(MDA)与超氧化物歧化酶(SOD)的含量。苏木素-伊红染色(HE)观察肾脏病理改变。原位缺口末端标记法(TUNEL)与DNA电泳观察肾小管上皮细胞的凋亡。Western印迹检测caspase-3的蛋白表达。结果 顺铂组大鼠BUN、Scr、尿NAG升高;肾脏病理改变加重;大量的肾小管上皮细胞凋亡; MDA含量增加,SOD活性降低;caspase-3的蛋白表达增加。上述指标在卡维地洛治疗组均得到改善,BUN从(58.33±19.93)降至(28.74±19.62)mmol/L;Scr从(425.56±97.96)降至(253.90±134.87)μmol/L;NAG从(224.77±75.86)降至(137.52±26.38)U/L;MDA从(18.13±7.01)降至(9.74±1.68)nmol/mg蛋白;SOD从(30.05±12.20)升至(64.67±20.64)U/mg蛋白;caspase-3的蛋白表达从1.94±0.73降至1.25±0.52;细胞凋亡从(42.5±12.6)%降至(23.7±8.4)%;肾组织病理损害也明显改善。结论 肾小管上皮细胞凋亡是顺铂致ARF的重要原因之一。卡维地洛能减轻顺铂的肾毒性,降低肾小管上皮细胞凋亡,其机制可能与减少活性氧(ROS)的产生,部分抑制了caspase依赖的凋亡途径有关。     

A focus of tissue necrosis increases renal susceptibility to gentamicin administration

The purpose of this study was to determine whether a retained focus of necrotic tissue predisposes to aminoglycoside-induced acute renal failure (ARF). Rats were subjected to either (1) 25% liver ligation, creating a focus of ischemic tissue which was left in place; (2) 25% liver resection; or (3) sham liver ligation. Gentamicin, 80 mg/kg bid, was administered for two days after surgery to all three groups. A fourth group was subjected to 25% liver ligation but no gentamicin therapy. Only rats subjected to partial liver ligation plus gentamicin treatment developed ARF, manifested by azotemia (BUN 80 +/- 2; creatinine 1.63 +/- 0.21; mg/dl) and tubular necrosis. This occurred in the absence of any discernible reduction in arterial blood pressure, renal blood flow, excessive weight loss, or ascites formation. The partial liver ligation-gentamicin group had 70% higher renal gentamicin concentrations than the liver resection-gentamicin controls (P = 0.01). To assess whether factors released from necrotic liver might account for these findings, additional rats were infused with: (1) 1 ml of a soluble liver extract alone; (2) 1 ml of liver extract plus gentamicin; or (3) 1 ml of saline plus gentamicin. Only the liver extract/gentamicin group developed ARF (BUN 88 +/- 13; creatinine 1.46 +/- 0.25). This occurred in association with a 110% increase in renal gentamicin uptake (P less than 0.03). In separate experiments, 5 ml liver extract infusions caused ARF (BUN 118 +/- 7; creatinine 2.1 +/- 0.18) without gentamicin treatment. In conclusion, a focus of liver necrosis can predispose to experimental gentamicin nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Augmentor of liver regeneration ameliorates renal tubular epithelial cell injury after rat liver transplantation

Background

Acute renal insufficiency and dysfunction are common complications after clinical liver transplantation. This study examined whether augmentor of liver regeneration (ALR) played a significant role to ameliorate renal tubular epithelial cell injury after liver transplantation.

Methods

Orthotopic liver transplantation was performed from Sprague-Dawley (SD) to SD rats. Twelve recipients were randomly divided into two groups: ALR group (with recombinated human ALR 100 μg/kg  ·  d intramuscular injection postoperation) versus normal saline-treated group (with the same volume of normal saline injected intramuscularly postoperation). Rats were sacrificed at day 3 posttransplantation. Renal morphological changes in recipients were assessed with light microscopy. The expressions of tumor necrosis factor-α (TNF-α), proliferating cell nuclear antigen (PCNA) and caspase-3 protein and mRNA in the kidney were evaluated by real-time polymerase chain reaction and immunohistochemical staining.

Results

Morphological changes in renal tubular epithelial cells were not significant in either group at day 3 posttransplantation. The intragraft expression of TNF-α and caspase-3 was strikingly promoted in the normal saline-treated group and PCNA attenuated compared to the ALR group.

Conclusion

These data suggested that ALR may play a role to reduce renal damage in liver transplant recipients.     

Urinary marker for oxidative stress in kidneys in cisplatin-induced acute renal failure in rats.

BACKGROUND: Establishment of non-invasive urinary biomarkers for the prediction of acute renal failure (ARF) is important. We evaluated whether urinary oxidative stress markers reflect intrarenal oxidative stress in cisplatin (CDDP)-induced ARF, and whether these markers can be used for the prediction of future ARF. METHODS: Urinary malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured up to day 14 post-CDDP (6 mg/kg) injection in rats. MDA and 8-OHdG expressions were examined in kidneys. RESULTS: CDDP induced an increase in serum creatinine (Scr), blood urea nitrogen (BUN), and tubular damage at day 5, increased urinary MDA excretion and MDA expression in kidneys at day 1 (but returned to basal values by day 3), increased urinary excretion of 8-OHdG at day 5 till day 14 (though the number of 8-OHdG-positive tubular cells increased at day 5 and then gradually decreased). Urinary MDA levels at day 1 correlated significantly with Scr (rho = 0.721, P < 0.01) and tubular damage score (rho = 0.840, P < 0.01) at day 5. CONCLUSION: Our findings demonstrated divergent changes of urinary oxidative stress markers in CDDP-induced ARF, and suggested that urinary MDA may be a useful marker for the prediction of the development of CDDP-induced ARF.     

Phlorizin-induced glycosuria does not prevent gentamicin nephrotoxicity in rats

Because rats with streptozotocin-induced diabetes mellitus (DM) have a high solute diuresis (glycosuria of 10 to 12 g/day), we have suggested that this may in part be responsible for their resistance to gentamicin-induced acute renal failure (ARF). The protection from gentamicin nephrotoxicity was studied in non-diabetic rats with chronic solute diuresis induced by blockage of tubular glucose reabsorption with phlorizin (P). DM rats with mild glycosuria (similar in degree to that of the P treated animals) were also studied. Unanesthetized adult female, Sprague-Dawley rats were divided in four groups and studied for 15 days. Group 1 (P alone) received P, 360 mg/day, for 15 days; Group II (P + gentamicin); Group III (gentamicin alone) and Group IV (mild DM + gentamicin). Nephrotoxic doses (40 mg/kg body wt/day) of gentamicin were injected during the last nine days of study to the animals of groups II to IV. In Group I, P induced a moderate and stable glycosuria (3.9 +/- 0.1 g/day, SE), and no functional or morphologic evidence of renal dysfunction (baseline CCr 2.1 +/- 0.1 ml/min, undetectable lysozymuria) or damage (tubular necrosis score [maximum 4], zero). In Group II, P did not prevent gentamicin-ARF (maximal decrease in CCr at day 9.89%, P less than 0.001; peak lysozymuria, 1863 +/- 321 micrograms/day; and tubular necrosis score, 3.9 +/- 0.1). These values were not different from those of Group III: maximal decrease in CCr 73% (P less than 0.001); lysozymuria, 2147 +/- 701 micrograms/day; tubular necrosis score, 3.8 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)     

阿托伐他汀调控PERK/eIF2α/CHOP通路减轻造影剂诱导的大鼠肾小管上皮细胞凋亡

目的研究造影剂肾病大鼠肾脏中葡萄糖调节蛋白78(GRP78)、内质网调节激酶(PERK)、真核起始因子2α(eIF2α)及C/EBP同源蛋白质(CHOP)的表达情况,探讨内质网应激在造影剂肾病发病中的作用及阿托伐他汀的干预作用。 方法60只大鼠随机分为4组：对照组、模型组和高、低剂量阿托伐他汀组(80 mg,40 mg),每组15只。分别于注射造影剂后24、48、72 h留取血清;检测各组大鼠的血清尿素氮(BUN)、血清肌酐(Scr);TUNEL法及Western印迹法测casepase-3的表达检测肾小管上皮细胞凋亡;免疫组化和Western印迹法检测各组大鼠肾组织GRP78、p-eIF2α、p-PERK及CHOP的表达。 结果与对照组相比,模型组大鼠BUN、Scr显著升高,细胞凋亡严重,GRP78、p-eIF2α、p-PERK及CHOP的表达均显著升高(P< 0.05);与模型组相比,高、低剂量阿托伐他汀组,BUN、Scr显著下降,凋亡指数降低,GRP78、p-eIF2α、p-PERK及CHOP的表达显著下调,但仍高于对照组,差异均达到统计学意义(P<0.05);高、低剂量阿托伐他汀组之间上述各指标差异均不显著。 结论PERK/eIF2α/CHOP通路介导的内质网应激可能参与大鼠造影剂肾病的发生发展;阿托伐他汀在造影剂诱导的肾脏损伤中发挥保护作用,这可能与其调节PERK/eIF2α/CHOP通路,从而减轻内质网应激有关。