肾疏宁防治系膜增殖性肾炎大鼠的肾小球病理形态研究

目的观察中药肾疏宁对系膜增殖性肾炎(MsPGN)的肾小球损伤的影响。探讨肾疏宁防治肾小球硬化的作用机制。方法制作大鼠MsPGN模型。将Wistar大鼠随机分为正常组、模型组、肾疏宁治疗组和苯那普利治疗组,观察肾脏形态学,共观察12、16周。结果 肾疏宁能明显改善肾组织病理病变,且对损伤的肾组织有修复作用,与模型组及苯那普利组相比,有显著差异。结论肾疏宁能减轻MsPGN的肾小球病变。     

全反式维甲酸对环孢素诱导的肾小球系膜细胞增殖与凋亡的影响及其机制

目的  探讨全反式维甲酸（ATRA）对环孢素（CsA）诱导的大鼠肾小球系膜细胞增殖及凋亡的影响及机制。方法  采用不同剂量ATRA作用于不同剂量CsA诱导下的肾小球系膜细胞。采用MTT比色法检测细胞增殖,Hoechst 33258荧光染色观察细胞凋亡形态,后用流式细胞仪检测细胞凋亡率,免疫荧光法检测线粒体促凋亡的Smac蛋白的表达。结果  与对照组比较,CsA剂量为0.5 μg/mL及以上可抑制细胞増殖,CsA剂量为1.0 μg/mL及以上可诱导细胞凋亡,且Smac蛋白的表达随CsA剂量的增加而增加,具有剂量和时间依赖的特征（均为P＜0.05）。而与CsA组比较,CsA+ATRA处理组对细胞增殖的抑制作用更为明显,而加入ATRA可呈剂量依赖性抑制CsA诱导的肾小球系膜细胞凋亡及Smac蛋白的表达（均为P＜0.05）。结论  CsA可抑制肾小球系膜细胞增殖,诱导其凋亡并刺激Smac蛋白的表达。ATRA可以抑制CsA诱导的肾小球系膜细胞凋亡,且可能是通过Smac信号通路介导的。     

足细胞损伤在预测肥胖相关性肾病发生中的价值

目的 研究肥胖相关性肾病患者肾小球足细胞病变,借助足细胞特异标记物Wilm肿瘤蛋白,分析其与蛋白尿、肾功能及肾组织病理形态学改变之间的关系.方法 15例经肾穿刺活检明确诊断的肥胖相关性肾痛.借助足细胞特异标记物采用免疫组织化学染色检查,对肾组织病理定量计数肾小球足细胞数.同时结合临床和肾组织病理有关指标的多因素进行分析.对照组5例,外科切除的且已诊断为肥胖的肾脏肿瘤标本的正常皮质组织.结果肥胖相关性肾病患者无论临床表现为小量蛋白尿组8例:24小时尿蛋白定量<1.0 g;中等量蛋白尿组4例:24小时尿蛋白定量1.0～3.5 g,大量蛋白尿组3例:24小时尿蛋白定量>3.5 g,与对照组比较肥胖相关性肾病患者均伴肾小球足细胞数目及密度的减少(均P<0.01),其中以大量蛋白尿组最为显著,中等量蛋白尿组次之,小量蛋白尿组最轻.足细胞数目及其密度与尿蛋白量呈显著负相关(r=0.664,P<0.01).足细胞数目的 减少还与肾小球病理改变相关,表现为肥胖相关性局灶节段性肾小球硬化症者其足细胞数目明显少于肥胖相关性肾小球肥大症者(P<0.01),足细胞融合、微绒毛化改变较多,肾小球硬化数明显增多(P<0.05).此外,足细胞数目减少严重者肾小球硬化(r=-0.427,P<0.05)以及血清肌酐水平升高的发生率均明显增高(r=-0.574,P<0.01).结论 肥胖相关性肾病患者早期就表现出肾小球足细胞数目及其密度的减少,随着病变的加重,这种变化愈发明显.足细胞病变不仅导致大量蛋白尿的发生,而且还与肾小球硬化和肾功能损伤的发生有关.     

慢性砷中毒对肾小球细胞凋亡形态学影响

目的 研究慢性砷中毒对肾小球细胞形态及细胞凋亡的影响。方法 复制慢性砷中毒大鼠模型,用苏木素-伊红(HE)染色、免疫组化细胞凋亡染色(Tunel法)观察肾小球形态学及细胞凋亡的变化,用图像分析计数。结果 慢性砷中毒大鼠肾血管充血、间质水肿、肾小球细胞数量增多、肾小球凋亡细胞核深染、固缩。砷中毒高剂量组及低剂量组肾小球细胞凋亡较对照组肾小球细胞凋亡明显增多,分别为(34.10±6.49),(1.50±1.18),(10.27±3.51),(1.50±1.18)。结论 慢性砷中毒可致肾小球细胞增殖,也与肾小球细胞凋亡增加有关。     

Cisplatin nephrotoxicity and protection by silibinin

BACKGROUND: The anticancer drug cisplatin is known to have toxic side-effectson different segments of the nephron. The flavonoid silibininhas previously been shown to be protective in models of hepatotoxicity.The aim of the present study was to evaluate, whether silibinincan also ameliorate alterations in renal glomerular and tubularfunction and tubular morphology induced by cisplatin. METHODS: In a rat model renal damage was induced by a single injectionof cisplatin (5 mg/kg body weight). The protective effects ofsilibinin were studied in rats that received the flavonoid (200mg/kg body weight, i.v.) 1 h prior to the administration ofcisplatin. Kidney function was monitored by analysing urinarymarkers of glomerular and tubular function over a period of11 days. Animals of a second group, with identical treatment,were sacrificed 4 days after drug application for an evaluationof tubular morphology at the light-microscopical level. RESULTS: Administration of cisplatin caused a decline in kidney functionwithin a day following treatment. Symptoms observed were forexample decreases in creatinine clearance and increases in proteinuria,in the urinary activity of the proximal tubular enzymes alanineaminopeptidase and N-acetyl-ß-D-glucosaminidase andin renal magnesium wasting. The effects of cisplatin on creatinineclearance and proteinuria were totally prevented by a pretreatmentof the animals with silibinin. Impairment of proximal tubularfunction was ameliorated, that is enzymuria and magnesium wastingwas less pronounced. Silibinin alone had no effect on kidneyfunction. Treatment with silibinin distinctly diminished morphologicalalterations observed in the S₃-segment of the proximal tubule4 days after cisplatin administration. CONCLUSIONS: The effects of cisplatin on glomerular and proximal tubularfunction as well as proximal tubular morphology could totallyor partly be ameliorated by silibinin. It is concluded thatsilibinin can act as a nephroprotectant and it is suggestedthat it could have beneficial effects on the kidney in clinicalsettings.     

Con-A诱导的抑制性细胞对肾小球多阴离子的影响

将大白鼠的外周血淋巴细胞分别用 Con-A 和 PHA 刺激;并分别与大白鼠低温肾切片共同孵育24h 后,用胶性铁染色检查肾小球多阴离子(GPA)。发现 Con-A 诱导的鼠淋巴细胞能减少 GPA 的染色能力,而 PHA 诱导的淋巴细胞,未经诱导的淋巴细胞、Con-A 诱导的单核细胞和 Con-A 诱导的淋巴细胞上清均无此作用。此结果与人类微小病变型肾病综合征的病理损伤有相似之处。     

AGEs/RAGE/SphK1信号通路介导马钱苷抗AGEs损伤GMCs的机制研究

目的 探讨山茱萸中有效成分马钱苷在缓解晚期糖基化终末产物（AGEs）诱导肾小球系膜细胞（GMCs）损伤的机制。方法 体外培养GMCs,分为空白对照组,模型组（AGEs:200mg/L）,马钱苷0.1、1、10μmol/L浓度组。检测细胞增殖率、细胞FN及COL-Ⅳ分泌水平,观察细胞微观结构变化,测定RAGE、SphK1、S1P和TGF-β蛋白表达量。结果 马钱苷可有效抑制AGEs诱导的GMCs增殖,减少FN及COL-Ⅳ分泌,缓解细胞微观结构病变,下调RAGE、SphK1、S1P和TGF-β蛋白表达。结论 马钱苷通过下调AGEs/RAGE/SphK1信号通路,缓解AGEs诱导的GMCs损伤,从而改善糖尿病肾病（DN）。      

Biologic modulation in renal regeneration

ABSTRACT

Introduction: Chronic kidney disease (CKD) is recognized as a health care problem of increasing importance. Following the discovery of renal progenitors, the investigation of new therapeutic approaches to promote the kidney regenerative capacity has received increasing research attention.

Areas covered: The authors discuss the current knowledge of glomerular regeneration by renal progenitors and the modulation of their behavior through chemical and biological agents. The regenerative capacity of renal progenitors after injury must be regulated in order to prevent an inefficient or excessive response that could lead to a failed attempt to replace lost podocytes. In addition, they discuss the most relevant pathways involved in tubular repair and how these could be modulated in order to obtain renal regeneration rather than progression of a fibrotic maladaptive response.

Expert opinion: Modulation of the endogenous renal regenerative capacity is a new approach in the treatment of kidney diseases. Research efforts that concentrate on the potential regenerative capacity of the kidney can be advantageous when the experimental results are translated into clinical practice and may open the way to new therapeutic strategies for CKD.     

小鼠胚胎肾小球滤过膜早期发育的超微结构

目的　观察小鼠胚胎肾小球滤过膜早期发育。方法　应用透射电镜观察小鼠胚龄 10、14、18d时肾小球超微结构改变。结果　毛细血管侵入S小体第一弯曲时诱导足细胞分泌基膜 ,然后足突、毛细血管内皮孔出现 ,内皮产生基膜 ,最后内皮基膜与足细胞产生和基膜融合成一层共有的基膜。结论　毛细血管诱导足细胞分泌基膜之后再诱导足突产生 ;足细胞基膜和足突出现后内皮才发育成有孔型内皮 ,并开始分泌内皮基膜 ,最终两层基膜融合为一层     

高浓度氨基酸对大鼠肾小球系膜细胞增殖及细胞外基质合成的影响

目的 观察高浓度氨基酸、高糖、高浓度氨基酸高糖混合物对系膜细胞增殖及细胞外基质合成的影响。 方法 采用噻唑蓝（MTT）法、流式细胞仪法观察甘露醇（13.3 mmol/L）、高浓度氨基酸(较DMEM氨基酸浓度高1.5~6倍，渗透浓度13.3 mmol/L)、高糖（30.5 mmol/L）、高浓度氨基酸高糖混合物分别对系膜细胞增殖的影响；RT-PCR方法检测转化生长因子β1（TGF-β1）、Ⅳ型胶原(ColⅣ)和纤连蛋白（FN）mRNA的表达水平； 酶联免疫法检测TGF-β1水平；Western印迹法及放射免疫法测定ColⅣ、FN蛋白表达。 结果 （1）高浓度氨基酸、高糖、高浓度氨基酸高糖混合物均能刺激系膜细胞增殖，且具有时间依赖性，作用48 h时细胞增殖最明显；而高浓度氨基酸高糖混合物刺激细胞增殖作用最强。（2）高浓度氨基酸高糖混合物与细胞作用48 h，能明显影响细胞周期，使G0/G1期细胞减少，S期细胞增加。（3）高浓度氨基酸、高糖、高浓度氨基酸高糖混合物均能上调系膜细胞TGF-β1的基因表达；促进 TGF-β1蛋白合成增加[单位ng&#8226;ml－1&#8226;（105细胞）－1]（3023±85、3163±80、3321±85比1506±63，均P < 0.05)。（4）高浓度氨基酸、高糖、高浓度氨基酸高糖混合物均能上调系膜细胞ColⅣ、FN的基因表达；促进ColⅣ蛋白合成增加[单位ng&#8226;ml－1&#8226;（105细胞）－1]（16.78±2.56、18.65±2.56、22.83±2.45比10.22±2.54，均P < 0.01)；也可促进FN蛋白合成增加(18.47±2.34、13.58±3.13、17.98±2.56比8.22±2.54，均P < 0.05)。结论 高浓度氨基酸有类似于高糖样促系膜细胞增殖作用，可能通过TGF-β1通路促进细胞活性增加，细胞外基质分泌增多，且与高糖有协同作用。