X线造影剂的肾毒性

近年来随着Ｘ线造影剂的大量使用，由造影剂而诱发的各种副反应不断增多，特别是造影剂导致的肾功能损害或原有肾功能损害的加重越来越受到人们的关注，作者结合近年文献资料，综述了造影剂的肾毒性作用及其机制，发生造影剂肾病的危险因素，造影剂肾毒性的预防。     

X线造影剂的肾毒性

近年来随着Ｘ线造影剂的大量使用，由造影剂而诱发的各种副反应不断增多，特别是造影剂导致的肾功能损害或原有肾功能损害的加重越来越受到人们的关注，作者结合近年文献资料，综述了造影剂的肾毒性作用及其机制，发生适影剂肾病的危险因素，造影剂肾毒性的预防。     

己酮可可碱对大鼠睾丸扭转复位后生精功能的保护

目的:探讨己酮可可碱(PTX)对大鼠睾丸扭转复位后生精功能的保护作用。方法:雄性SD大鼠24只,随机分成3组,每组8只,建立睾丸扭转动物模型。第Ⅰ组为假手术组(扭转720°后立即复位),第Ⅱ、Ⅲ组扭转720°2 h,于复位前15 m in分别静脉注射生理盐水和PTX,术后24 h留取手术侧睾丸。应用流式细胞术(FCM)检测各组生精细胞凋亡和各级生精细胞计数,采用硫代巴比妥酸法测定丙二醛(MDA)含量,化学比色法测定组织内总抗氧化能力(T-AOC)。结果:第Ⅲ组应用PTX后与第Ⅱ组相比,生精细胞凋亡明显减少(399.50±33.31vs1221.75±132.48,P<0.01),单倍体和四倍体细胞群计数显著增多(5554.13±441.28vs4102.35±206.98;1906.00±200.72vs1711.63±144.55,P均<0.01;),T-AOC明显回升(32.52±2.86vs22.76±3.73,P<0.01),MDA含量下降(1.78±0.20vs3.98±0.36,P<0.01),其差异均有显著性(P<0.01)。结论:己酮可可碱对睾丸扭转复位后的生精功能具有明显的保护作用。     

己酮可可碱对脓毒症大鼠急性肺损伤的保护作用及机理

目的：探讨己酮可可碱（PTX）对腹腔感染致脓毒症时急性肺损伤的保护作用及其机理。方法：采用盲肠结扎穿孔致脓毒症模型,将42只大鼠随机分为对照组6只,脓毒症组18只和PTX治疗组18只,检测肺组织生物喋呤（BH4）合成限速酶－三磷酸鸟苷环水解酶Ⅰ（GTP－CHI）,诱生型一氧化氮合酶（iNOS)和肿瘤坏死因子－α（TNF－α）mRNA的表达,同时测定肺组织BH4、一氧化氮（NO）的含量及髓过氧化物酶（MPO）活性的变化。结果：脓毒症早期给予PTX治疗可有效抑制腹腔感染后2、8h肺组织TNF－α mRNA表达和伤后2h MPO活性;同时,治疗组2h肺组织BH4,NO含量及GTP－CHI mRNA,iNOS mRNA表达均显著降低。结论：早期应用PTX对脓毒症后急性肺损伤具有明显保护作用,该效应与PTX抑制BH4,NO的诱生相关。     

己酮可可碱对自由基致心肌损伤的保护作用及其机制

目的：观察己酮可可碱（ｐｅｎｔｏｘｉｆｙｌｉｎｅ，ＰＴＸ）对自由基损伤心肌的作用和机制，方法：采用外源性氧自由基灌注致大鼠心肌损伤，观察自由基射前，后不同时间阶段的心功能及血清丙二醛，乳酸和肌酸激酶含量的改变，结果：氧自由基注射后５分，心肌＋ｄｐ／ＩＩｐ由有药前３４±２．７ｓ＾－１降至１９±６．８ｓ＾－１（Ｐ〈０．０１），１小时后仍无明显好转（Ｐ〈０．０５），血清丙二醛，乳酸及肌酸激酶的含量明显升     

己酮可可碱对沙鼠全脑缺血／再灌注的保护作用

目的　观察己酮可可碱 (PTX)对沙鼠全脑缺血 /再灌注模型的作用效果 ,并对其作用机制进行初步探讨。方法　夹闭双侧颈动脉 ,诱导沙鼠全脑缺血 ,30分钟后松夹 ,再灌注 90min。在缺血诱导时 ,静脉给予 2 5mg·kg-1,或者 5 0mg·kg-1的PTX ;另一组于再灌注开始时静脉输注 2 5mg·kg-1的PTX。假手术组和对照组输入相同容积的 0 9%NaCl。再灌注开始时以 0 2 %伊文思兰 1ml·10 0g-1对所有沙鼠腹腔注射。实验结束时断头取脑 ,- 70℃冰箱保存 ,进行脑水肿定量、脑组织超氧化物歧化酶 (SOD)活性、丙二醛 (MDA)含量测定及脑组织伊文思兰含量测定。结果　与对照组相比 ,在缺血诱导时或再灌注开始时输注 2 5mg·kg-1PTX明显减轻沙鼠脑水肿的程度 (P <0 0 5或0 0 1) ,脑组织脂质过氧化产物MDA含量显著降低 (P <0 0 5或 0 0 1) ,脑组织中SOD的活性明显升高 (P <0 0 5或 0 0 1) ,脑组织伊文思兰含量显著降低 (P <0 0 5或 0 0 1)。 5 0mg·kg-1PTX输注对沙鼠脑缺血 /再灌注损伤无保护作用 ,其中 3只沙鼠死于低血压休克。结论　在血液动力学稳定的前提下 ,PTX对脑缺血 /再灌注损伤的保护作用可能与其提高脑血流量 ,抑制超氧阴离子产生 ,以及对血管内皮细胞的保护作用有关     

缬草油对高胆固醇血症大鼠肾间质纤维化的改善作用及机制探讨

目的观察缬草油对高胆固醇血症大鼠肾间质纤维化的改善作用并探讨其可能机制。方法将64只SD大鼠随机分为正常组、高脂组、缬草油组和辛伐他汀组,每组16只。缬草油组给予缬草油25mg·kg^-1·d^-1灌胃,辛伐他汀组同时给予辛伐他汀5mg·kg^-1·d^-1灌胃。比较各组大鼠总胆固醇（TC）、甘油三酯、低密度脂蛋白（LDL）、高密度脂蛋白、24h尿蛋白量、血肌酐（SCr）、肾间质损伤指数及转化生长因子β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）mRNA和蛋白表达。结果与高脂组相比,第16周时缬草油组肾小管间质损伤指数降低,TC、LDL、24h尿蛋白量和SCr降低,差异均有统计学意义（P〈0．01）。与正常组相比,第8周时,高脂组肾小管内TGF-β1表达增多,差异有统计学意义（P〈0．01）,而α-SMA表达未见明显升高;第16周时,TGF-β1表达更为明显,α—SMA表达明显增加,差异均有统计学意义（P〈0．01）。缬草油能显著降低各时间点TGF-β1、rSMA蛋白和mRNA表达,其改善作用较辛伐他汀更明显。结论缬草油可改善高脂血症大鼠肾间质纤维化,可能与其调节血脂,下调肾组织TGF-β1表达,抑制肾小管上皮细胞转分化有关。     

宽叶缬草对高胆固醇血症大鼠肾脏保护作用的探讨

目的 :探讨宽叶缬草在脂质肾损害中的保护作用和可能机制。方法 :用含 4 %胆固醇和 1%胆酸钠的高脂饲料饲喂大鼠建立高脂模型 ,观察宽叶缬草对大鼠血脂、尿蛋白和肾功能的影响 ,以及对肾小球系膜细胞增殖、细胞外基质增生、α -SMA表达、Ⅳ型胶原表达的影响。结果 :宽叶缬草有降低总胆固醇、低密度脂蛋白和尿蛋白的作用 (P <0 .0 1) ,肾病理和免疫组化证实宽叶缬草在降脂和降低尿蛋白同时 ,能减轻肾小球系膜病变和细胞外基质产生 ,降低肾小球α -SMA和Ⅳ型胶原表达。结论 :宽叶缬草的肾保护作用可能与降脂基础上的肾小球系膜细胞表型转化的抑制有关     

缬草油对高胆固醇血症大鼠肾小管上皮细胞巢蛋白表达的影响

目的：探讨缬草油对高胆固醇血症大鼠肾小管上皮细胞巢蛋白表达的影响。方法：大鼠随机分为正常组、高脂组、缬草油（25mg·kg-1.d-1）组和辛伐他汀（5mg·kg-1.d-1）组,用含4%胆固醇和1%胆酸钠的高脂饲料饲喂大鼠建立高脂模型。观察8、12、16周时各组大鼠血脂、尿蛋白、血肌酐和肾小管间质病理改变,免疫组化法检测肾小管上皮细胞巢蛋白和α-平滑肌肌动蛋白（α-SMA）表达。结果：随时间延长,高脂大鼠肾小管上皮细胞逐渐出现巢蛋白和α-SMA表达。巢蛋白表达与总胆固醇、低密度脂蛋白、24h尿蛋白、血肌酐正相关（r=0.963、0.830、0.944、0.706,P〈0.01）,与肾小管间质损伤指数正相关（r=0.974,P〈0.01）,与α-SMA呈正相关（r=0.804,P〈0.01）。缬草油能显著降低大鼠血总胆固醇、低密度脂蛋白、24h尿蛋白和血肌酐,下调肾小管上皮细胞巢蛋白和α-SMA表达（P〈0.01）。在巢蛋白表达减少同时,肾小管间质损伤和纤维化明显改善,其改善作用较辛伐他汀更明显（P〈0.05）。结论：缬草油可能通过降脂、下调肾小管上皮细胞巢蛋白表达减轻高胆固醇血症大鼠肾间质纤维化。     

己酮可可碱对精子活力的体外改善作用

目的体外分析己酮可可碱(Pentoxifylline，PF)对精子活力的改善作用，探讨PF最佳作用浓度和时间，为实施人工授精奠定基础。方法本实验就PF的不同浓度(0．6mmol／L、3．0mmol／L)和不同时间(30min，60min)，恒温下与70例弱精子的体外孵育，并与对照比较，观察精子活力特性的改善情况。结果PF的不同浓度及不同时间对精子活力均有改善作用，而用PF的0．6mmol／L浓度、孵育30min，对体外弱精子的活力有显著增强作用。结论PF对体外弱精子的活力有改善作用，药物浓度和作用时间直接影响孵育效果。     

非离子型对比剂对人血管内皮细胞活力和凋亡影响的实验研究

目的观察不同浓度非离子型对比剂对人脐静脉血管内皮细胞活力的影响。方法采用MTT实验分析不同浓度非离子对比剂对脐静脉血管内皮细胞的作用,并通过测定细胞凋亡率,探讨对比剂影响细胞的方式及影响程度。结果各处理组内细胞凋亡均明显增高（P〈0.01）;对比剂浓度因素对血管内皮细胞活力影响显著（P〈0.01）。结论体外培养环境下非离子对比剂在一定浓度下会对血管内皮细胞造成活力影响并增加细胞凋亡率;但不同类型非离子型对比剂欧乃派克及威视派克对血管内皮细胞的影响无明显差别。     

Effects of pentoxifylline in Adriamycin-induced renal disease in rats

Tumor necrosis factor- (TNF-) is a mediator of inflammation in human and animal renal disease. Pentoxiphylline (PTX) is an inhibitor of TNF-. In this study we examined the effects of PTX on TNF-, proteinuria, nitrite production, and apoptosis in an experimental model of Adriamycin (ADR) nephropathy in rats. Rats were divided into four groups: untreated Wistar rats (controls), PTX treatment alone, ADR treatment alone to induce nephropathy, and ADR treatment followed by PTX. ADR treatment followed by PTX treatment prevented the increase in serum TNF- levels and proteinuria in rats with ADR-nephropathy (P<0.05). Urine nitrite levels were significantly increased in the ADR-induced nephropathy group and the increase was prevented in the ADR-induced nephropathy group when they also received PTX. The urine nitrite levels were not different between the PTX-treated group and the untreated control rats. PTX prevented the rise of serum TNF- in ADR nephropathy rats and a decrease in proteinuria, urine nitrite, and apoptosis in the renal tissue. These findings suggest a beneficial anti-inflammatory effect of PTX.     

Nephrotoxic effects of ionic and nonionic contrast media on rat and human renal cortical slices

Background. Nephrotoxicity is a well-known adverse effect of radiographic contrast medium (CM). Recently, several kinds of low- osmolality nonionic CM have been developed. However, the nephrotoxic effects of nonionic CM compared with those of ionic CM have not been well evaluated. Methods. To compare the direct nephrotoxic effects of ionic and nonionic CM on renal epithelial cells, rat and human renal cortical slices were incubated with CM at 37°C for 120 min. Diatrizoate and iothalamate were employed as ionic CM. Iopamidol, iohexol, iomeprol, ioversol, iopromide, and ioxilan were employed as nonionic CM. Direct toxicity of CM was evaluated by the activities of N-acetyl-β-D-glucosaminidase (NAG) and γ-glutamyl-transferase (GGT) released from the renal slices into the incubation buffer. Results. In the experiment with rat renal slices, NAG and GGT activities in buffer solutions were increased dose-dependently by 30, 60, and 90 mg I/ml of CM. There was no significant difference in NAG or GGT release between ionic and nonionic CM at the concentration of 60 mg I/ml. In the experiment with human renal slices, incubation with 60 mg I/ml of diatrizoate, iothalamate, iomeprol, and iopromide did not affect NAG levels. Significantly greater increases in NAG levels, compared with the control, were observed after incubation with iopamidol, iohexol, ioxilan and ioversol. Nevertheless, the increases in NAG caused by some of the nonionic CM were very slight. GGT release from human renal slices was significantly greater than that of the control in all experimental groups. Again, there was no significant difference in renal toxicity between ionic and nonionic CM. Conclusions. Newly developed nonionic CM had almost the same degree of nephrotoxicity against rat and human renal epithelial cells as conventional ionic CM, when direct renal toxicity was evaluated by enzyme release in an in-vitro experimental system using renal cortical slices. Received: November 22, 2000 / Accepted: March 6, 2001     

脂质微泡造影剂的制备方法及其应用的研究进展

脂质微泡是近年来国内外研究的热点之一。脂质微泡不仅是一种良好的超声造影剂,而且在医药实验研究及临床治疗方面应用较广泛,本文就其制备方法及应用的研究进展进行简述。     

超声微泡造影剂介导基因转染的研究进展

基因治疗疾病的有效性主要取决于基因转染率,基因转染载体包括病毒载体和非病毒载体。超声微泡造影剂为一种新型非病毒载体,介导基因转染具有安全、靶向、目的基因转染率高等优点,本文对近年来超声微泡造影剂介导基因转染的研究进展进行综述。     

Early glomerular effects of contrast media in rats: Evaluation with a simple method

The aim of this study was to evaluate the early effects of high and low-osmolar contrast media on glomerular function in rats by using a new method based on the measurement of the urinary excretion of ^99mTc-DTPA. Thirty-six Sprague-Dawley male rats were examined: nine rats were injected with diatrizoate (ionic high-osmolar contrast medium), nine rats with iohexol (nonionic low-osmolar contrast medium), nine rats with iopamidol (nonionic low-osmolar contrast medium), and nine rats with saline as controls. The urinary excretion of ^99mTc-DTPA in the first minutes after i.v. injection was assumed as an index of glomerular filtration rate. A lower urinary excretion of ^99mTc-DTPA was found in rats treated with contrast media in comparison with control rats. This effect was more evident after diatrizoate but was statistically significant also after iohexol.

In conclusion, a reduction in the glomerular filtration rate probably occurs in the first few minutes after contrast media administration. The measurement of urinary excretion of ^99mTc-DTPA could be a simple method to detect acute glomerular effects due to contrast media or to other drugs.     

高渗和低渗造影剂对人肾小管上皮细胞的毒性作用

目的 比较高渗造影剂（HOCM，泛影葡胺）和低渗造影剂（LOCM，欧乃派克）对人肾小管上皮细胞的毒性，探讨Bax／Bcl-2，半胱氨酸天冬氨酸蛋白酶（caspase）-3在造影剂诱导肾小管上皮细胞凋亡中的作用。方法 以HKC细胞株为研究对象，实验分为7组：HOCM1组（111mgI／ml），HOCM2组（74mgI／m1），LOCMl组（111mgI／m1），LOCM2组（74mgI／ml），甘露醇高渗对照组，甘露醇低渗对照组，培养基对照组。采用四甲基偶氮唑蓝（MTT）试验和乳酸脱氢酶（LDH）检测造影剂对体外培养HKC细胞的毒性作用。采用Hoechst染色、TUNEL染色、DNA琼脂糖凝胶电泳、电镜和流式细胞仪DNA分析方法观察造影剂对HKC细胞凋亡的作用。采用Westem印迹方法检测Bax和Bcl-2蛋白含量的变化。采用荧光比色法检测caspase-3活性。结果 HOCM和LOCM组培养液中LDH水平较对照组显著增高（P〈0．05），细胞活力较对照组显著降低（P〈0．05），且与渗透浓度，作用时间及碘离子浓度有关。HOCM可诱导肾小管上皮细胞凋亡，且明显高于甘露醇高渗对照（P〈0．05）。LOCM在本实验剂量不能诱导肾小管上皮细胞凋亡。HOCM在诱导HKC细胞凋亡时伴随有Bax、Bcl-2表达的上调，caspase-3活性升高。结论 HOCM和LOCM对肾小管上皮细胞均有毒性作用，LOCM的毒性作用明显小于HOCM。HOCM可诱导人肾小管上皮细胞凋亡且与高渗及碘离子浓度有关。Bax／Bcl-2、caspase-3可能参与了造影剂诱导人肾小管上皮细胞凋亡的调控。     

The protective effect of hydroxytyrosol on contrast - induced nephropathy and endoplasmic reticulum stress

Objective To investigate the expression of glucose-regulated protein 78(GRP78) and cysteine aspartic acid protease 12(Caspase - 12) and evaluate the endoplasmic reticulum stress (ERS) in rats with contrast - induced nephropathy (CIN), and observe the protective effects of hydroxytyrosol on CIN rats. Methods Eighty-four Wistar rats, (220±20) g, were randomly divided into control group, CIN group, hydroxytyrosol treated group (group C+H). At 12th, 24th, 48th, 72th day after the rats model were established, BUN and Scr were detected. ELISA were used to detect the expression of methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). HE staining were used to evaluate the pathological change of kidney. TUNEL were used to detect the apoptosis of tubular cells. Real-time PCR were used to detect the expression of GRP78 mRNA and Caspase-12 mRNA in tubular cells. Immunohistochemistry and Western blotting were used to detect the expression of GRP78 and Caspase - 12 protein in tubular cells. Results BUN, Scr, the mRNA and protein expression of GRP78, Caspase-12 in hydroxytyrosol treated group were higher than that in control group(P＜0.05), but were significantly lower than that in CIN group (P＜0.05). Pathological changes and the apoptosis of tubular cells in CIN group were more serious than that in hydroxytyrosol treated group (P＜0.05). Conclusions Endoplasmic reticulum stress may be associated with contrast-induced nephropathy. Hydroxytyrosol can protect kidney from contrast medium via reducing the endoplasmic reticulum stress.     

Nephrotoxicity of high- and low-osmolality contrast media

Nephrotoxicity of radio-opaque contrast media (CM) is generally believed to involve toxic injury of proximal tubular cells. Measurement of urinary tubular enzyme excretion has been advocated as a sensitive marker of such toxic injury. It has been claimed that the new low-osmolality or nonionic CM reduce the incidence of nephrotoxicity but this remains uncertain. We studied 23 patients with normal renal function undergoing coronary angiography; patients were randomized into three groups receiving either diatrizoate (1,800 mmol/kg H2O), ioxaglate (600 mmol/kg H2O) or iohexol (850 mmol/kg H2O). Urinary excretion of a panel of enzymes increased significantly in all groups by 20 h (p less than 0.05 to less than 0.005). Alanine aminopeptidase excretion at 20 h was greater after the administration of high osmolality ionic CM than with the others but all three CM produced a similar pattern of enzyme excretion. No significant change in glomerular filtration rate was found in any group so the significance of the enzymuria remains uncertain.