高渗和低渗造影剂对大白鼠肾毒性的实验研究

目的 :研究高、低渗造影剂对甘油致肾损害大鼠和正常大鼠的肾毒性 ,观察山莨菪碱预防肾小管损害的作用。方法 :用 2 5 %甘油按 1ml/ 10 0 g制肾损害大鼠模型 ,然后从静脉注射高渗造影剂 (76 %复方泛影葡胺 ,1ml/ 10 0 g)或优维显 (1m l/ 10 0 g) ,2 4h后各组随机处死 10只大鼠 ,肾脏用 10 %福尔马林固定后做病理检查。结果 :在肾功能损害组 ,给高渗造影剂后 ,可使肾小管管型数和肾小管坏死数明显高于低渗造影剂组和甘油对照组 (P<0 .0 1) ,山莨菪碱可明显减轻肾小管损害 (P<0 .0 5 )。正常肾功能组高、低渗造影剂组之间肾小管损害无显著性差异。结论 :肾功能损害时用低渗造影剂对肾毒性较小 ,山莨菪碱对复方泛影葡胺的肾毒性有一定的预防作用。     

普乐可复对肾脏毒性的实验研究

目的 :探讨普乐可复 (FK5 0 6 )对肾脏的毒性及其机制。方法 :分别给小鼠腹腔注射生理盐水、FK5 0 6 5mg·(kg·d) -1和 10mg·(kg·d) -1,连续用药 7d后断头采血 ,检测血肌酐 (Cr)、尿素氮 (BUN)、血栓素 B2 (TXB2 )和 6 酮 前列腺素F1α(6 keto PGF1α) ,并剖腹取其肾脏行常规病理检查。结果 :FK5 0 6 5mg·(kg·d) -1组血清BUN、Cr、TXB2明显高于空白对照组 (P均 <0 0 5 ) ,6 keto PGF1α较之显著降低 (P <0 0 5 ) ;光镜下可见肾近曲小管上皮细胞混浊肿胀 ,肾小球萎缩不明显。FK5 0 6 10mg·(kg·d) -1组血清BUN、TXB2明显高于FK5 0 6 5mg·(kg·d) -1组 (P <0 0 5 ) ,6 keto PGF1α显著降低 (P <0 0 5 ) ;光镜下可见肾小球萎缩 ,纤维化 ,严重者肾小球结构消失 ,肾近曲小管上皮细胞混浊肿胀。结论 :FK5 0 6的肾毒性主要表现为肾小球和肾小管损伤后的肾功能下降 ,其机制与肾脏血管内皮细胞损伤有关     

高脂饮食诱导的高胆固醇血症对雄性Wistar大鼠肾脏的毒性作用

目的 研究高胆固醇血症对雄性Wistar大鼠肾脏的毒性作用。方法 用5%胆固醇饲料喂养雄性Wistar大鼠,制备高胆固醇动物模型,分别于实验第30、60和90d测定肾功能、24h尿蛋白、肾皮质胆固醇（Ch）及各磷脂含量,并进行病理形态及组织定量分析。结果 在实验周期内实验组（E组）大鼠血浆肌酐水平无显著变化;第90d,E组24h尿微量白蛋白、肾皮质Ch、磷脂酰胆碱（PC）及磷脂酰乙醇胺（PE）显著高于正常对照组（C组）;病理形态及组织定量分析显示肾小球系细胞增垂、炎性细胞浸润、系膜基质增多、毛细血管塌陷、上皮细胞足突融合,肾小球体积增大。IgG直接免疫荧光阴性,肾小球内无电子致密物沉积。相关分析显示肾小球体积、肾皮质Ch含量及24h尿微量白蛋白排泄率等与血浆总胆固醇（TCh）及低密度脂蛋白（LDL）浓度呈显著正相关关系。结论 饮食诱导的高胆固醇血症可导致Wistar大鼠肾毒性损伤。     

中药肾毒性成分及其毒性机制研究进展

近年来,随着我国医药产业的稳步发展,中药作为补充和替代医学制剂在世界各地赢得了认可和信赖。然而,随着对中药的广泛应用和深入研究,中药的肾脏毒性引发了国内外学者的广泛关注。为保障中药临床应用的安全性,有必要深入研究并整理中药肾毒性成分及其毒性机制。在查阅近30年国内外常见中药肾毒性相关文献的基础上,对中药肾毒性成分及其毒性机制进行了总结与分析,以期为中药肾毒性深入研究提供思路,为中药安全合理应用提供参考。     

Pathological excretion patterns of urinary proteins in renal cell cancer patients exposed to trichloroethylene

A study was carried out to investigate urinary protein excretion patterns by means of SDS-polyacrylamide-gel-electrophoresis (SDS-PAGE) in renal cell cancer patients who had previously been exposed to high levels of trichloroethylene. Thirty-eight out of 41 (93%) renal cell cancer patients investigated had former extensive trichloroethylene exposure, but only 23 out of 50 (46%) renal cell cancer patients without a history of occupational exposure to trichloroethylene revealed urinary protein patterns indicative of toxic effects on the tubular system. One hundred controls without histories of overt renal disease and not occupationally exposed to trichloroethylene were examined in the same way; only 11 (11%) of them displayed protein excretion patterns indicative of damage to the renal tubule. These results are supported by alpha 1-microglobulin excretion data. The following conclusions are drawn: (1) Substantially more cases of tubular damage are found amongst renal cell carcinoma patients having been exposed to substantial levels of trichloroethylene over many years as compared with renal cell carcinoma patients not exposed to trichloroethylene. (2) The results support the view that chronic tubular damage is a precondition for the nephrocarcinogenic effect of trichloroethylene. (3) The findings indicate that urine protein patterns, on the basis of the SDS-PAGE methodology, represent a 'biological effect parameter' for the medical surveillance of persons occupationally exposed to trichloroethylene.     

The Effect of Parenterally Administered Cyclodextrins on Cholesterol Levels in the Rat

The inclusion complex formation of intravenously administered hydroxypropyl--cyclodextrin and -cyclodextrin with endogenous lipids was studied. We tested the hypothesis that complex formation of endogenous cholesterol with cyclodextrins in the bloodstream leads to extraction of cholesterol from the large lipoprotein particles. The relatively small cholesterol–cyclodextrin complexes then leave the bloodstream via capillary pores, and dissociation of the complex in the extravascular compartment finally causes redistribution of cholesterol from blood to tissue. This hypothesis is supported by the following experimental findings. Intravenous administration of cyclodextrins led to a transient decrease in plasma cholesterol levels in a dose-dependent manner, and in vitro cholesterol-cyclodextrin complexes passed dialysis membranes with a molecular weight cutoff of 6000–8000. Further, cyclodextrins increased protein binding of the steroidal drug spironolactone, probably through removal of cholesterol from plasma protein binding sites. Finally, extravascular redistribution was directly demonstrated in histological studies of the kidneys. Glomerular filtration of the cholesterol–cyclodextrin complex is followed by dissociation of the complex in the ultrafiltrate, resulting in cholesterol accumulation in the proximal tubule cells. The cholesterol--cyclodextrin complex has a limited aqueous solubility. Crystallization of this complex in renal tissue might explain the nephrotoxicity of parenterally administered -cyclodextrin. The absence of such crystallization might explain the lower nephrotoxicity of hydroxypropyl--cyclodextrin after intravenous administration.     

左旋精氨酸预防大剂量顺铂急性肾毒性的剂量探讨

目的探讨左旋精氨酸预防大剂量顺铂急性肾毒性的最佳剂量。方法选择128例肿瘤病人,随机分为A、B、C3组,3组病人顺铂的剂量及用法相同,均为100mg/m2,分两天(第1、2天)给药。3组病人左旋精氨酸的用量分别为每天5g/m2、10g/m2和15g/m2,于化疗的当天在顺铂后应用,每例病人加与不加精氨酸周期的两周期化疗形成自身对照,每例病人化疗前及化疗后24h均检测尿β2-MG、血尿素氮(BUN)、血肌酐(Cr)及血尿酸,观察3组病人加与不加精氨酸周期化疗前后各观察指标的变化,并比较3组的疗效。结果血BUN、Cr及尿酸无论在加精氨酸周期还是在不加精氨酸周期,化疗前后检测值均无明显变化,该3项指标不宜作为早期急性肾功能损害的检测指标。而A、B、C3组病人化疗后的尿β2-MG值在加与不加精氨酸周期分别为0.9120±0.6618与1.5167±0.7908(P<0.05)、0.5404±0.5810与1.4616±0.8120(P<0.01)及0.4998±0.6210与1.5210±0.7710(P<0.01),均有明显差别,B组的结果差别极其显著,C组的结果差别也极其显著。A、B、C3组的显效率及总有效率分别为40.9%及59.1%、68.2%及90.9%、77.5%及97.5%,经X2检验,A、B两组的显效率及总有效率均差别显著,B、C两组的显效率及总有效率均无显著性差别。结论左旋精氨酸有效预防大剂量顺铂急性肾毒性的最佳剂量为每天10g/m2,增加剂量并不增加疗效。     

奈达铂（Nedaplatin）在大鼠体内的肾毒性和骨髓抑制的时辰毒理学研究

目的:以大鼠为实验对象,通过测定给药时间与奈达铂(Nedaplatin)诱发的肾毒性和骨髓抑制的关系,研究铂(Pt)衍生物奈达铂的时辰毒理.方法:于8:00或20:00通过尾静脉给S-D大鼠(n=8)注射奈达铂(5 mg/kg体重)或空白溶媒,给药间隔为7天.定期采血、采尿测定血清肌苷清除率和周边血中的中性粒细胞.最后一次给药后24小时,处死动物,采集肾脏和大腿骨用于Pt浓度测定和组织学检查.共给药6次.结果:20:00给药组的体重抑制明显高于8:00给药组,实验结束时,两实验组均有2只动物死亡.奈达铂诱发的骨髓抑制没有明显的给药时间相关性,但20:00给药组的肾毒性明显大于8:00给药组.肌苷清除率和肾组织损伤积分均与肾皮质中n的含量有很好的相关性.结论:奈达铂诱发的肾毒性和药物在组织中的蓄积与给药时间有很好的相关性,提示该类药物在临床使用过程中应注意给药时间的选择.     

Effects of low‐dose melamine exposure during pregnancy on maternal and fetal kidneys in rats

Despite the previous reports on melamine contamination in high concentrations some years ago, there were not many studies on low‐level exposure in daily life, particularly in pregnancy. We investigated the effect of low‐dose melamine on the kidneys of the pregnant rats and their developing embryos/fetuses during various gestational stages namely implantation, gastrulation, organogenesis, maturation and whole pregnancy. Our results showed that the repeated low level of melamine (12.5, 25, and 50 mg/kg bw/d) during pregnancy did not cause obstruction of renal tubules although more precipitating crystals were found in the early gestational periods. Simple hyperplasia in the maternal tubules and pelvic epithelium were more prominent after exposed to melamine during the whole gestational period. Neonatal kidneys significantly suffered more from congestion in glomeruli and interstitium, dilated tubules and interstitial edema after melamine administration to the mother in the late and the whole gestational periods. A trend of advance of glomerular development in fetuses was also observed. We conclude that in utero exposure of low‐level melamine could post a risk on the kidneys of the pregnant mother as well as the developing fetuses, which may further increase the possibility of other health problems later in life.     

Cisplatin toxicity reduced in human cultured renal tubular cells by oxygen pretreatment

Abstract

Cisplatin is an effective and widely used chemotherapy agent and its side effects, particularly nephrotoxicity, limit its usage and related platinum-based drugs. Cisplatin nephrotoxicity is mainly due to extremely increase in reactive oxygen species (ROS) generation leading to kidney tubular cell death. Preconditioning with oxidative stress has been demonstrated to stimulate the cellular adaptation to subsequent severe oxidative stress. Short term oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on Cisplatin induced cell death was investigated in present research. We studied the effects of hyperoxic environment pre-exposure on Cisplatin toxicity in an in-vitro model of cultured human embryonic tubular epithelial cells (AD293). Viability of AD293 cells, as evaluated by MTT-assay, was affected by Cisplatin in a time (1–4?h) dependent model. Biochemical markers of cell apoptosis were evaluated using immunoblotting. Pretreatment with nearly pure oxygen (≥90%) for 2?h significantly reduced the level of cell damage. Activated caspase 3 and Bax/Bcl-2 ratio were significantly increased in Cisplatin-treated cells. Oxygen pretreatment inhibited caspase 3 activation and decreased Bax/Bcl-2 ratio. Oxygen pre-treatment itself not showed any cytotoxicity in exposure times up to 3?h. Our data indicate that hyperoxic preconditioning reduces Cisplatin toxicity in cultured human tubular epithelial cells. The exact mechanism of protection is unclear, though enhancement of some endogenous defense mechanisms and subsequently scavenging of free oxygen radicals may play an important role.