应用铈细胞化学方法镉诱发氧自由基对肾脏的损伤

目的 研究镉及其诱发的氧自由基对肾脏的急性损伤。方法 应用民镜细胞化学及能量色散谱分析技术。结果 镉离子可进入到肾近曲小管上皮细胞内,肾组织内有氧自由基的过量 产生,基 于血管内皮细胞,肾近曲小管上皮细胞的线粒体,微绒毛及其底膜等部位。肾近曲小管上皮细胞及细粒体可发生肿胀及内皮细胞脱落等病变。结论 镉离可导致氧自由基的大量形成,从面对肾脏造损伤。     

尿N—乙酰—β—D—氨基葡萄糖苷酶对诊断汞镉铅肾损害的意义

汞,镉,铅等重金属都对肾脏有毒性作用,主要影响肾近曲小管,但临床表现潜隐,早期不易发现.尿醇是新近发展起来的反映肾小管上皮细胞损伤的敏感指标.N-乙酰-β-D-氨基葡萄糖苷酶(NAG)是存在于细胞溶酶体中的一种糖苷水解酶,体内以肾脏含量最丰富,在肾内又以肾近曲小管含量最多.肾近曲小管上皮细胞损伤时,尿中NAG 活性迅速增加,可比较灵敏地反映肾小管上皮细胞的损伤.本实验目的在于研究尿NAG 对汞、镉、铅所致肾脏损伤的诊断意义.     

亚慢性镉中毒肾损伤的超微病理观察

研究表明:病变早期近曲小管上皮细胞线粒体肿胀、嵴减少或破裂,胞浆有较多细小空泡,溶酶体增多,并见“多泡膜层体”;随后近曲小管上皮坏死,多泡膜层体增多,刷状缘溃烂脱失,质膜皱褶破坏,核变形,肾小球内皮细胞、足细胞及远曲小管上皮细胞变性,病变后期胶原纤维广泛增生,肾硬化萎缩。肾皮质镉含量进行性升高,镉离子因与金属硫蛋白及其他金属结合蛋白结合,故电子探针X—线波谱扫描分析未见游离镉富集现象。     

氯化镉诱导大鼠肾细胞系细胞凋亡的研究

镉(Cadmium)是重要的工业和环境污染物之一，美国毒物药理委员会(ATSDR)将其列为第6位危害人体健康的有毒物质。镉对肾、肝、脑、睾丸、骨髓及血液系统均可产生毒性，其中肾脏是镉最重要的蓄积部位和靶器官，长期、低剂量接触镉可引起肾脏近曲小管上皮细胞损伤，导致肾脏近曲小管重吸收功能降低。目前，有关镉的肾损伤机制研究已经进入分子水平，其中，镉致细胞凋亡就是一个方面。本研究以正常大鼠肾细胞系(NRK)为研究对象，     

亚慢性镉中毒大鼠肾组织超微结构改变

目的 对亚慢性镉中毒大鼠的肾组织进行超微结构检查。方法 SD大鼠腹腔注射0.8mg·kg~(-1)·d~(-1)CdCl_2溶液(相当于0.8mgCd~(2+)),每周5次,共4周。取肾组织常规制片,透射电镜下观察。结果 镉中毒大鼠肾近曲小管上皮细胞、线粒体肿胀,嵴断裂,肾小球系膜细胞增生,足突间隙融合,鲍曼氏囊腔狭窄、毛细血管瘀血及间质纤维化,肾远曲小管上皮细胞肿胀、崩解,线粒体水肿、膜破裂。结论 亚慢性镉染毒除引起肾近曲小管上皮细胞出现超微结构病理改变外,对肾小球和肾远曲小管上皮细胞也产生严重损害。     

镉诱导猪肾近曲小管上皮细胞LLC-PK1的凋亡

镉(Cd)是环境和食物链中主要的的重金属污染物之一。动物实验和人群流行病学研究均表明镉可产生严重的毒性效应。大剂量、急性镉中毒可致肝、肺和睾九的损伤。而长期低剂量接触镉主要引起以近曲小管损害为主要特征的肾脏损害。体内动物实验研究表明，镉引起肾细胞凋亡是镉肾毒性的分子机制之一。近年来体外实验研究镉诱导肾细胞凋亡的分子毒理学机制已取得一定的进展。但尚未完全清楚。本研究选用猪肾近曲小管上皮细胞(LLC-PK1)为实验对象，观察了氯化镉对该细胞的毒性效应，以及诱导LLCPK1细胞凋亡的作用与细胞周期变化的影响，为进一步阐明镉诱导肾细胞凋亡及其分子机制提供依据。     

硒拮抗氟诱导肾脂质过氧化及酶组织化学改变的研究

给ＳＤ大鼠饮用含氟化钠，亚硒酸钠，氟化钠和亚硒酸钠的水溶液８周，观察硒对氟诱导肾脏脂质过氧化及肾酶组织化学改变的影响。结果表明，氟可使肾脏脂质过氧化物含量明显增加，并可使肾近曲小管上皮细胞琥珀酸脱氢酶（ＳＤＨ）和碱性磷酸酶（ＡＬＰ）活性明显降低，乳酸脱氢酶（ＬＤＨ）和酸性磷酸酶（ＡＣＰ）活性明显增高。同时补硒可促进肾脏的氟排泄，降低肾脏脂质过氧化物含量，对氟引起的生物膜损伤具有较强的防护作用，从而减轻氟对肾近曲小管上皮细胞中ＳＤＨ、ＡＣＰ活性的影响，而硒对氟所致的肾近曲小管上皮细胞ＡＬＰ、ＬＤＨ活性改变的拮抗作用则不明显。可以认为，硒对氟致肾损害具有一定拮抗作用。     

甘草甜素和齐墩果酸对镉中毒肾损害的影响

目的 观察甘草甜素（GL）和齐墩果酸（OA）对大鼠亚慢性镉中毒性肾损害组织病理形态的影响。方法中光镜、电镜下观察CdCl2组、CdCl2＋GL组、CdCl2＋OA组大鼠肾组织内肾小球、肾近曲小管的病理改变。结果 光镜下，CdCl2＋GL组、CdCl2＋OA组大鼠肾小球充血、肿胀、纤维化、肾近曲小管上皮细胞肿胀的程度较CdCl2组明显减轻，范围有所缩小。超微结构观察示药物共处理组肾小球内组分、肾近曲小管细胞内线粒体等亚细胞组分的病变显轻于CdCl2组。结论 GL、OA对大鼠亚慢性CdCl2中毒性肾损伤的病理形态损伤有改善作用。     

苯乙烯急性肾脏毒性实验研究

本文初步探讨了苯乙烯对大鼠的急性肾脏毒性作用。结果表明，染毒七天后，２０００ｍｇ／ｋｇ组大鼠肾脏器系数和尿量明显增加；各染毒组尿γ－ＧＴ和ＡＫＰ活性比对照组显著增高；２０００．１０００ｍｇ／ｋｇ组尿β２－ｍ含量和ＧＯＴ活性亦明显增高。电镜下可见２０００ｍｇ／ｋｇ组肾近曲小管上皮细胞线粒体肿胀、嵴溶解或消失，有数量不等的空泡和圆形密体形成，提示苯乙烯急性染毒可对大鼠产生肾脏毒性，主要局限肾近曲小管。     

镉在大鼠肝亚细胞颗粒中的形式

镉摄入后主要蓄积在肝和肾。大部分蓄积镉集中在细胞浆的可溶部分并同金属硫蛋白相结合,仅少量分布在线粒体和溶酶体内。然而给大鼠饮含CdCl_2的水,用电镜可观察到肾近曲小管细胞线粒体肿胀及溶酶体增加。大鼠喂以含CdCl_2的食物,肝线粒体呼吸控制受抑。这些变化究竟是溶酶体金属硫蛋白降解释放镉离子或由镉硫蛋白所引起有待研究。本文研究了镉在肝线粒体和溶酶体内的形式。     

镉染毒后肾小管上皮细胞内氧自由基代谢与损伤之间关系的研究

本文以离体肾小管上皮细胞为研究对象，观察了镉致肾小管上皮细胞损伤时细胞内氧自由基反应及其与细胞超微结构改变之间的关系。结果表明，镉可诱发离体肾小管上皮细胞脂质过氧化反应增强，脂质过氧化产物明显增加，超氧化物歧化酶及过氧化氢酶活性显著受抑，与此同时肾小管细胞出现一系列超微结构改变；抗氧化剂ＶｉｔＥ可使脂质过氧化作用明显减弱。提示镉臻肾小管上皮细胞损伤与氧自由基对细胞膜结构及功能的损伤有关，氧自由基在     

Hyperplastic changes in the rat distal tubular epithelial cells following in utero exposure to methylmercury

Female Sprague—Dawley rats were injected with 1.0 mg methylmercury chloride on the eighth day of pregnancy. Tissues from the renal cortex of the offsprings were sampled for electron microscopy. Besides degenerative changes in the proximal convoluted tubules, hyperplastic changes were observed in the distal convoluted tubules. Increased mitotic index was found in many distal tubular epithelial cells. Hyperplastic thickening of these tubular linings was also observed. Such hyperplastic changes may be suggestive of premalignant changes.     

铅中毒大鼠肾近曲小管内铅的分布

前人在铅中毒动物肾近曲小管上皮细胞内发现有核内包涵体。这种包涵体曾被认为含有铅.本实验用含铅饲料饲养大鼠一个月后取肾皮质,进行超微结构和X射线显微分析研究。在超薄切片中观察到,肾近曲小管上皮细胞核内有包涵体形成,管腔中可见电子致密斑块。X射线显微分析结果指出,于包涵体的中心区和周边区以及溶酶体和胞质基质中都不产生pb元素峰。只在管腔中的致密斑块中,能产生PbLa峰和CaKa峰。表明致密斑块是铅中毒动物肾内铅沉积部位。而其核内包涵体中并未见铅的沉积,它可能是细胞对铅中毒性作用的反应产物。     

硒对氟所致肾脏病理和超微结构改变的影响

采用组织病理学和电子显微镜技术，研究了大鼠同时接触氟化钠和亚硒酸钠对肾脏的形态学影响．结果表明，氟化物对肾脏具有明显的损害作用，可使肾近曲小管上皮细胞浊肿、水变性和坏死．肾小管上皮细胞线粒体数目增多、肿胀，线粒体嵴减少、消失及坏死．细胞内次级溶酶体增多，局部胞浆崩解．粗面内质网扩张，肾小管上皮细胞基底膜局部增厚，上皮细胞游离面微绒毛肿胀，排列紊乱．同时给予硒和氟的大鼠，肾脏的组织病理学和超微结构改变均较单纯加氟组明显减轻．可以认为，硒对氟致肾损害有明显的拮抗作用，其机理可能与硒的抗氧化作用有关．     

慢性砷中毒对大鼠肾近曲小管上皮细胞凋亡表达的影响

目的探讨慢性砷中毒对大鼠近曲小管上皮细胞凋亡表达的影响。方法将30只健康成年清洁级SD大鼠随机分为高(10.0mg/kg)、低(0.4mg/kg)剂量砷染毒组和对照(蒸馏水)组,采用经口自由饮用方式进行染毒,日饮水量约为200ml/kg,连续染毒6个月。染毒结束后,取大鼠肾脏进行HE染色和PAS染色,采用免疫组化法(TUNEL细胞凋亡染色法)测定大鼠近曲小管上皮凋亡细胞计数及其灰度值。结果砷中毒大鼠近曲小管上皮细胞空泡样变性,细胞腔面刷状缘减少并脱落,可见细胞核固缩、深染,有较多凋亡细胞,染色质浓缩聚集于核膜下。与对照组比较,高、低剂量砷染毒组大鼠肾近曲小管上皮凋亡细胞计数增高,灰度值较低,差异均有统计学意义(P0.05)。随着砷染毒剂量的增高,大鼠肾近曲小管上皮凋亡细胞计数呈增多趋势,灰度值呈降低趋势。结论慢性砷中毒可引起大鼠近曲小管上皮细胞凋亡。     

Pathological changes in the kidney after methyl cadmium intoxication

Adult male cats with an average body weight of 3 k were injected with 3.0 mg methylcadmium every other day for 10 days (a total of five injections were given). The kidneys were studied for degenerative changes. Lipid accumulation and cellular casts within the tubular lumen could be observed both light and electron microscopically. By electron microscopy, severe enlargement of the apical vacuoles, accumulation of microbodies, sloughing of the microvilli, and extrusion of cytoplasmic masses into the tubular lumen were also observed. The degenerative changes were mainly found in the proximal convoluted tubules (PCT) while the distal tubules only showed minimal signs of degeneration. Flattening of the basal infoldings was also observed in many PCT epithelial cells which also showed deposition of a layer of basal filamentous dense materials. Fusion of the foot processes of the glomerular epithelial cells (podocytes) was also a prominent finding. Such a lesion in the glomeruli was believed to be associated with the severe proteinuria found in cadmium poisoning, In generaly, the methylcadmium appeared to be even more nephrotoxic than inorganic cadmium, and its toxic potential as an environmental hazard deserves more attention.     

An ultrastructural reevaluation of lead-induced pathology in the kidney

The renal pathology of rats injected with daily doses of 10.0 mg/kg body wt lead acetate was studed. Animals were sacrificed after 4 weeks of treatment and the renal cortices were sampled for pathological evaluation. No significant morphological lesion was observed in the control animals injected with saline solution. Light-microscopic examination of the lead-treated animals showed degenerative and necrotic changes in the proximal tubules. Intranuclear inclusion bodies could also be observed. Extensive morphological changes were revealed by electron microscopy. The most prominent lesions were observed in the pars recta segment of proximal tubules. Accumulation of lysosomes, particularly at the apical portion of the cells, was observed. Some of these lysosomes attained giant sizes of 8–10 μm in diameter. Matrical swelling of mitochondria was also a frequent finding. Besides the typical intranuclear lead inclusion bodies, pseudonuclear inclusions derived from extensive invaginations of the nuclear envelope were also found. Edematous dilation of the inter-cellular interdigitational spaces giving rise to sieve-like structures within epithelial cells were a common finding. Splitting of the basement membrane to form microspherical particle-filled pockets was also a prominent change in proximal tubules. This report presents a detailed reevaluation of morphological lesions produced in the kidney by inorganic lead. The various toxicopathological changes produced by lead may be used as a model for future studies of renal toxicants.     

Degenerative changes in the neonatal kidney following in-utero exposure to methylmercury

Pregnant Sprague—Dawley rats were injected with 4.0 mg Hg/kg body weight of methylmercuric chloride on the 8th day of pregnancy. Tissue samples from the kidneys of the offspring were obtained for electron microscopic examination. Degenerative changes in the epithelial cells of the proximal convoluted tubules (PCT) including accumulation of lysosomes, enlargement of the apical vacuoles, cytoplasmic vacuolation, and extrusion of large cellular casts into the tubular lumen were observed. Flattening of the basal infolding was found in some PCT epithelial cells. Deposition of basal filaments in these cells were also observed. Extrusion and embedding the spherical microparticles into the basement membranes of the PCT was also a prominent finding. No degenerative changes were seen in the distal tubules. However, degeneration of the Bowman's capsule of the glomeruli, fusion of the epithelial foot-processes, and detachment of the glomerular epithelial cells from their basement membranes could be observed occasionally.     

Ultrastructural studies on the pathological change in the neonatal kidney following in utero exposure to halothane.

Pregnant rats were exposed to 10 ppm halothane all through pregnancy in specially designed chambers. The ultrastructure of the kidneys from neonatal rats was studied. Most of the lesions were found in the proximal convoluted tubules (PCT). Flattening or loss of the basal infoldings of the epithelial cells was a prominent finding. Disorientation of the mitochondria, basal accumulation of lipid droplets, increase in lysosomes, enlargement of apical vacuoles, and formation of clusters of SER were also observed in many PCT epithelial cells. Extrusion of cytoplasmic materials and large packages of cytoplasmic masses into the tubular lumen were also evident. Coagulative necrosis of the PCT was a frequent finding. Since the present experimental condition simulated the actual environmental condition in an average operating room, halothane may be considered to be an occupational hazard especially to the pregnant OR personnel.