镉性肾损伤超微结构的改变

目的 研究镉对大脏脏近曲小管线粒体的早期毒性作用。方法 用透射电镜观察不同剂量镉引起肾损伤的超微结构变化。结果 镉中毒早期损伤表现为肾近曲小管上以细胞线粒体肿胀,变形,继发溶酶体大量增加,并在吞噬线粒体后发生溶解,最后导致细胞坏死。实验结果表明该实验设计可用于制造镉性早期肾损伤的中毒模型。结论 低剂量镉引起肾近曲小管超微结构的早期变化呈明显的剂量－效应关系,具有可逆性。中毒阈剂量经为０．２ｍ／ｋｇ     

尿磷酸二酯酶I对汞性肾脏损伤的监测

目的对尿磷酸二酯酶I监测汞性肾脏损伤进行实验研究。方法用微量测定法测定汞作业工人和非职业性汞接触者尿磷酸二酯酶I活性的变化,并与尿蛋白和尿肌酐的变化进行比较。结果汞作业工人尿汞超标者尿磷酸二酯酶I活性显著升高,与对照组比较,有非常显著性意义（P<0.01）,非职业性汞接触者（包括皮肤接触和口服者）尿磷酸二酯酶I活性均显著高于对照组（P<0.01）;与Pr、Cr相比较,尿磷酸二酯酶I对汞性肾损伤的检测具有更高的敏感性。结论尿磷酸二酯酶I是一项能反映汞性肾损伤的敏感指标,对于早期诊断汞肾损伤有较高的临床应用价值。     

镉中毒性肾损伤时肾细胞内微量元素的改变

镉中毒性肾损伤时肾细胞内微量元素的改变龙曼海赵金垣刘爱萍（贵阳医学院预防医学系，贵阳５５０００４）为了解微量元素在镉中毒性肾损伤中的可能作用及机理，本研究采用１２０的氯化镉（ＣｄＣｌ２）与巯基乙醇的混合液制备镉中毒性肾损伤模型，测定不同时间的生物材料...     

一种改进的尿蛋白图谱测定法——不连续SDS-PAS垂直板电泳法

随着科学技术的发展,镉、汞等重金属的接触水平日趋降低,因此需要一种更敏感的早期诊断指标。尿蛋白类型的分析是一种无损伤鉴别性较强的肾损伤部位的监测方法,可作为镉、泵等毒物长期低剂量引起潜在性肾损伤的诊断指标。国外用超滤浓缩-SDS,圆盘电泳法,近年来国内用聚乙二醇和自制超滤膜浓缩尿液-     

实验性汞中毒时肾组织和尿中碱性磷酸酶活性的变化

本研究采用亚急性汞中毒肾损害的大鼠模型,探讨了汞中毒时血、肾和尿中碱性磷酸酶(ALP)活性的变化关系。结果表明,大鼠肾匀浆中 ALP活性明显低于对照组,尿 ALP活性则显著增加。ALP 活性降低的部位在肾近曲小管。体外实验未发现氯化汞对肾、尿ALP 具有直接抑制作用或激活作用。尿中ALP 活性的增高是汞引起的肾小管上皮细胞损伤所致。它可作为汞中毒肾损害的一个观察指标。     

实验室汞污染引起慢性轻度汞中毒1例报道

实验室汞污染引起的慢性轻度汞中毒,患者临床上出现头痛、头晕、全身乏力、手抖、睡眠欠佳、性格改变等症状,并有口腔溃疡、手颤(+)、尿汞增高,经驱汞治疗后症状减轻,诊断慢性轻度汞中毒。     

镉中毒肾损害大鼠尿中金属硫蛋白的变化

用Sephadex G-75凝胶层析技术对亚急性镉中毒肾损害大鼠肝、肾、血、尿中金属硫蛋白(MT)进行了分离测定。结果表明,大鼠接受镉后,其肝、肾、血、尿中MT增多;MT是体内镉的主要存在形式;尿中MT增多是镉中毒肾损害最早出现的变化之一,是肾小管功能障碍的灵敏指标,对反映镉性肾损害有其特异性。     

锌金属硫蛋白对镉中毒小鼠肾损伤的修复作用

目的：研究锌金属硫蛋白（Zn-MT）对镉中毒小鼠肾损伤的修复作用。方法：以昆明种小鼠作为研究对象，染镉14d建立亚急性镉中毒模型，随后经口给予Zn-MT。收集24h尿液，测定尿N－乙酰－β－D－氨基葡萄糖苷酶（NAG酶）活性作为衡量肾脏损伤程度的一项指标，同时电镜观察肾组织形态学变化；测定并分析肾组织上清液中脂质过氧化代谢产物一丙二醛（MDA）水平、超氧化物歧化酶（SOD）、谷胱甘肽过氧化酶（GSH－Px)活性。结果：Zn-MT可明显降低肾组织中MDA水平，使肾组织中SOD、GSH－Px活力有一定程度的恢复，此时尿NAG酶活性降低表明肾损伤程度减轻，且上述作用呈明显的剂量－反应关系；电镜下观察到给予Zn-MT后肾组织形态学病变有所减轻。结论：Zn-MT可对镉中毒小鼠肾组织脂质过氧化损伤起到一定的修复作用。     

松花粉对急性汞中毒大鼠肝肾的保护作用及机制研究

目的研究松花粉对急性汞中毒大鼠肝肾的保护作用及机制。方法将大鼠随机均分为正常对照组,染汞模型组,松花粉低、中、高剂量组(2、4、8 g/kg)。通过皮下注射HgCl_2建立急性汞中毒模型,末次染汞后,各组分别灌胃给予相应药物,2次/d,共5 d。通过电感耦合等离子体质谱仪,测定肝汞、肾汞、血汞和尿汞的含量。通过试剂盒,测定尿素氮(BUN)、尿蛋白、尿乳酸脱氢酶(LDH)、尿碱性磷酸酶(ALP),血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、血清总胆红素(TBIL),以及肝、肾中的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、谷胱甘肽(GSH)和丙二醛(MDA)的含量或活性。结果与正常对照组比较,染汞模型组大鼠的肝汞、肾汞、血汞、尿汞、BUN、尿蛋白、尿LDH、尿ALP、血清ALT、血清AST、血清TBIL、肾脏MDA和肝脏MDA含量或活性均升高(P<0.01),肾脏和肝脏SOD、GSH-Px、GSH含量或活性降低(P<0.01)。与染汞模型组比较,松花粉低、中、高剂量组大鼠的尿汞含量增加(P<0.05或P<0.01),上述其余指标均能显著地向正常对照组的数值变化(P<0.05或P<0.01)。结论松花粉具有清除体内汞蓄积、修复急性汞中毒诱导的急性肝肾损伤的作用,其机制与抑制脂质过氧化损伤相关。     

镉对去卵巢大鼠骨密度和肾功能的影响

目的：研究镉对去卵巢大鼠骨密度的影响及其与肾脏损伤的关系。方法：将SD大鼠行人工去卵巢术，分别经饮水给不同剂量的镉染毒，24周后处死。用双能量X线骨密度仪（HOLOGIC，QDR－4000）测定股骨颈、股骨中点及腰椎的骨密度，用石墨炉原子吸收法测定血、尿及骨镉，放免法测定血清雌二醇,同时测定镉肾损伤指标尿β2－微球蛋白和尿钙。结果：大鼠去卵巢后，体内雌二醇水平低下，骨密度明显下降。镉染毒可使大鼠股骨颈的骨密度明显降低，且随镉染毒剂量增加呈下降趋势。镉染毒后，大鼠发生肾损伤，尿β2－微球蛋白和尿钙含量升高。同时股骨颈的骨密度与肾损伤指标β2－微球蛋白有显著性相关。结论：镉染毒可降低去卵巢大鼠的骨密度，对股骨颈作用尤为敏感，而且镉引起的骨损伤与镉造成的肾损伤相关。     

大鼠亚慢性铬染毒引起的肾损害

30只Wistar♂大鼠ip K_2Cr_2O_7 1.06mgCr~(6+)/kg,每周5次,连续12wk。肾脏出现明显的形态和功能异常,早期肾小管上皮细胞出现变性,尿中N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、溶菌酶(LZM)和蛋白质的含量分别在染毒d2,3和5wk时显著增加;晚期肾小管上皮细胞出现广泛变性和坏死,尿中碱性磷酸酶(ALP)、γ-谷氨酰移换酶(γ-GT)和葡萄糖的含量分别在染毒d6,10和10wk时明显增加,GFR在染毒7wk开始下降。尿铬主要以低分子铬结合物(LW-Cr,5000道尔顿)形式排出。尿铬与肾损害程度显著相关,尿LZM、尿蛋白和GFR出现异常的尿铬临界浓度分别为5.90,7.57和9.36μg/mg肌酐。肾脏铬的蓄积则以高分子铬结合物(HM-Cr,65000道尔顿)和与尿铬相似的LM-Cr两种形式存在,主要蓄积在肾皮质。肾铬与肾损害相关密切,尿LZM和尿蛋白出现异常的肾皮质铬临界浓度分别为36.7ppm和41.8ppm。     

苯那普利与氟伐他汀单用及联用对阿霉素肾病大鼠单核细胞趋化蛋白-1的影响

目的探讨苯那普利与氟伐他汀单用及联用对阿霉素肾病大鼠单核细胞趋化蛋白-1(MCP-1)的影响。方法雄性SD大鼠120只,适应性喂养2周后,随机抽取18只为正常对照组(A组),另外102只制作阿霉素肾病模型。84只造模成功的大鼠随机分为4组:B组为模型对照组(生理盐水,3mL/d,n=21),C组为苯那普利治疗组[苯那普利3.5mg/(kg·d),n=21],D组为氟伐他汀治疗组[氟伐他汀10mg/(kg·d),n=21],E组为苯那普利与氟伐他汀联合治疗组[苯那普利3.5mg/(kg·d)+氟伐他汀10mg/(kg·d),n=21]。分别于2、6、10周末,遵循随机化原则,按n=6分层抽取各组样本,收集24h尿液、血液及肾脏标本待测。结果与B组比较,C组、D组及E组血清MCP-1及甘油三酯、胆固醇浓度均降低,24h尿蛋白减少;肾脏局部MCP-1的表达明显减少。E组疗效更为明显。结论苯那普利与氟伐他汀可以减轻阿霉素肾病大鼠蛋白尿,降低血清甘油三酯、总胆固醇及MCP-1浓度,抑制MCP-1在肾脏的表达,联用时疗效更好。     

金钗石斛对糖尿病大鼠肾组织中糖基化终产物表达的干预作用

目的研究金钗石斛对糖尿病(DM)大鼠肾组织中肾脏糖基化终产物受体(RAGE)表达的干预作用。方法将W istar大鼠随机分3组,用链脲佐菌素(STZ)建立DM模型,金钗石斛水煎剂10 g/(kg.d)灌胃给药12周后,肾组织病理切片HE染色观察肾组织病理变化;生化法测定血糖、尿蛋白、肌酐浓度;荧光光谱法测定尿液和血清糖基化终产物(AGE)含量;免疫组化检测肾组织RAGE蛋白;实时荧光定量PCR检测肾组织RAGE mRNA表达。结果金钗石斛可降低DM模型大鼠血糖,减轻肾脏损害,降低血清中AGE以及肾组织RAGE mRNA和蛋白表达水平。结论金钗石斛干预减轻DM肾脏功能损害可能通过降低血清中AGE和下调肾组织中RAGE表达而实现。     

维生素C对糖尿病大鼠肾脏醛糖还原酶活性的影响

目的 :探讨不同剂量维生素C对糖尿病大鼠肾脏醛糖还原酶(AR)活性的影响。方法 :体重195g 左右的雄性Wistar大鼠50只 ,随机分为5组 :C组 :正常对照组 ;D组 :糖尿病组 ;DT1 组 :糖尿病鼠 +维生素C30mg/(kg·d)组 ;DT2 组 :糖尿病鼠 +维生素C90mg/(kg·d)组 ;DT3 组 :糖尿病鼠 +维生素C270mg/(kg·d)组。实验第9wk检测血浆、肾脏维生素C水平和AR活性。结果 :与正常对照组比较 ,糖尿病组血浆、肾脏维生素C水平显著下降 (P<0 05) ,肾皮质AR活性明显升高 (P<0 01) ;3种剂量维生素C治疗组血浆、肾脏维生素C水平与正常对照组比较差异无显著性 ,AR活性较糖尿病组明显降低 (P<0 05)。结论 :补充维生素C可显著增加糖尿病大鼠血浆肾脏维生素C水平 ,明显降低糖尿病大鼠肾皮质AR活性。     

西洛他唑对糖尿病大鼠肾脏过氧化物酶体增生物激活受体γ表达的影响

目的探讨西洛他唑对高糖大鼠肾脏过氧化物酶体增生物激活受体γ(PPARγ-)表达的影响。方法雄性SD大鼠,链脲佐菌素(STZ)制备糖尿病模型。设正常对照组、糖尿病对照组及高[25 mg/(kg.d)]、低[18 mg/(kg.d)]剂量西洛他唑组,12周后处死动物,测血糖、糖化血红蛋白,肾重/体重,检测肾组织PPARγ-mRNA及蛋白质表达。结果与糖尿病组相比,西洛他唑无明显降低血糖作用;糖尿病对照组肾重/体重明显增加(P<0.01),西洛他唑有减轻肾肥大趋势;RT-PCR、Western blot结果显示西洛他唑能明显增强PPARγ-mRNA和蛋白质水平表达(P<0.05),高剂量组效果优于低剂量组,但无统计学差异。结论西洛他唑可能通过上调PPARγ-,对糖尿病肾脏具有保护作用。     

Tissue distribution of cadmium and nephropathy after administration of cadmium in several chemical forms

Cadmium (Cd) was administered as CdCl2, Cd-Cys, Cd-partial structural peptide of metallothionein (MT) II, Cd-MT I, and Cd-MT II to rats, and the distribution of and nephropathy caused by the corresponding Cd compounds were examined. Each Cd complex showed dissociation of Cd in vivo and in vitro in the plasma. With Cd-Cys approximately 80% dissociation was observed while Cd-MT showed only 15% dissociation. When the dissociation of the Cd complex in the plasma was less, the distribution of Cd to the liver was decreased but distribution was increased to the kidney and urine. Each Cd complex showed the presence of Cd in the kidney shortly after the administration in the high molecular weight fraction (HM-fr) and also in MT-fr. This was then followed by a decrease in the Cd level in the HM-fr but by an increase in the MT-fr. All Cd compounds except CdCl2 caused some transient renal damage. Renal damage shown by significant increases of urinary protein, glucose, and amino acids were observed at the doses of 1.3-1.7 mg Cd/kg in the Cd-Cys group, at 0.51-0.64 mg Cd/kg in the Cd-peptide group, and at 0.16-0.23 mg/kg in the Cd-MT I and II groups. The Cd level in the kidney of rats with renal damage from these complexes was approximately the same in all the groups, that is, 10 micrograms/g kidney. It is concluded that Cd causes renal damage when its concentration in the kidney is 10 micrograms/g or higher regardless of the type of Cd complex that is administered.     

Long-term oral intake of low-dose cadmium exacerbates age-related impairment of renal functional reserve in rats

Our study was designed to clarify whether renal functional reserve (RFR) was impaired in rats chronically treated with oral low-dose cadmium (Cd). Rats (n = 15) were treated with 1 ppm of cadmium chloride added to drinking water. We measured RFR (representing the ability to increase glomerular filtration rate [GFR] and renal plasma flow [RPF] in response to infusion of glycine) at 2 and 10 months after initiation of exposure to Cd. Urinary excretion of Cd was significantly higher in 10-month Cd-treated rats than in age-matched control rats (provided with distilled water only). Weight gain was noted in Cd-treated rats, which was identical to that in age-matched control rats. Urinary volume and urinary excretions of sodium, protein, and glucose were similar in the two groups. There were no differences in the basal mean arterial pressure (MAP) and renal hemodynamics between 2-month Cd-treated and age-matched control rats. Infusion of glycine resulted in significant increases in GFR and RPF and a significant reduction in renal vascular resistance (RVR) in both 2-month Cd-treated and age-matched control rats (control, GFR: 133 +/- 10%, RPF: 148 +/- 8%; 2-month Cd-treated rats, GFR: 152 +/- 12% and RPF: 154 +/- 7%). The basal MAP and renal hemodynamics in 10-month Cd-treated rats were also identical to those in age-matched control rats. Infusion of glycine significantly increased GFR in 10-month control rats (132 +/- 15%), but not in 10-month Cd-treated rats (98 +/- 11%), but did not change MAP, RPF, and RVR in both groups. In addition to age-related pathological changes, mild renal interstitial edema and degenerative mitochondria with diminished matrix density and loss of the cristae in the proximal tubular cells were more frequent in 10-month Cd-treated rats. Our results suggest that long-term oral intake of low-dose Cd in rats exacerbate age-related impairment of renal functional reserve and degeneration of the proximal tubular epithelial cells.     

托拉塞米与呋塞米治疗儿童肾病综合征伴高度水肿的疗效评价

目的:观察托拉塞米与呋塞米治疗儿童肾病综合征引起水肿的临床疗效。方法:选取54例儿童肾病综合征患儿,将54例患儿分为托拉塞米组、呋塞米加口服补钾组、呋塞米组各18例。三组患儿在激素及一般治疗的基础上,托拉塞米组给予静脉注射托拉塞米1 mg/(kg·d),每次不超过20 mg;呋塞米加口服补钾组给予静脉注射呋塞米2 mg/(kg·d),每次不超过40 mg,并口服补钾;呋塞米组给予静脉注射呋塞米2 mg/(kg·d),每次不超过40 mg。三组患儿分别于治疗前1 d、治疗后每天记录24 h尿量,治疗前及治疗后第4天抽外周血查电解质的变化情况,并记录不良反应。结果:三组患儿治疗后尿量较治疗前均显著增多,但治疗后前3 d平均尿量三组比较差异无统计学意义(P>0.05);呋塞米组治疗后第4天血钾浓度较其余两组降低明显(P<0.05);托拉塞米组和呋塞米加口服补钾组患儿治疗后第4天血钾浓度比较差异无统计学意义(P>0.05)。结论:临床上对于儿童肾病综合征引起的水肿应用托拉塞米或呋塞米治疗效果显著。应用呋塞米时同时口服补钾可减轻其致低血钾的不良反应。     

Acetaminophen nephrotoxicity in male Wistar rats

Acute acetaminophen (APAP) nephrotoxicity was studied in male Wistar rats 1 h after different APAP single doses (200, 500 and 1000 mg/kg body wt, i.p.). Significant impairments in glomerular filtration rate (GFR) and clearance ofp-aminohippuric acid (Cl_PAH) were observed in a dose-dependent way, although tubular parameters measured, water and electrolyte fractional excretion, remained at control values, while the urine to plasma osmolality ratios (U_osm/P_osm) were diminished in APAP-1000 rats (control=2.93 ±0.20, APAP-1000=1.40±0.04). The time course of renal function was also studied in APAP-1000 mg/kg-treated animals; parallel impairments were observed in GFR, Cl_PAH and tubular functions. Maximal alteration was observed at 16 h and restorement began at 24 h post-injection. Glucose renal handling, either at low or at high tubular glucose loads, remained at control values. Thus, our data suggest that the early stage of acetaminophen nephrotoxicity might be due to renal hemodynamic changes which might induce an alteration in tubular function principally in distal structures of medullary tissue, as shown by the U_osm/P_osm results. These effects occurred coupled with a diminution in hepatic glutathione (GSH) levels at every APAP dose and in renal GSH levels in APAP-1000 mg/kg-treated rats. Moreover, renal damage was observed both in the presence or absence of hepatic damage.     

肾康福液对大鼠慢性肾功能衰竭的预防、治疗作用和Ⅱ期临床试验

目的 :探讨肾康福液预防和治疗慢性肾功能衰竭 (肾衰 )的疗效。方法 :2 4只慢性肾衰大鼠模型随机分为 4组 :(1)空白对照组不给任何药物仅灌同容积水 ;(2 )阳性对照组灌服包醛氧化淀粉水溶液 (0 .5 g·kg- 1) 2mL ,tid ;(3 )治疗组灌服肾康福液 2mL ,tid ;(4)预防组在肾切除前 7d灌服肾康福液 ,剂量同治疗组。疗程均为 18wk。 2 40例慢性肾衰病人随机分为治疗组 12 0例 ,口服肾康福液2 0mL ,tid× 18wk ;对照组 12 0例口服包醛氧化淀粉 5～ 10 g ,tid× 18wk。结果 :肾康福液组大鼠和病人的肌酐、尿素氮、尿蛋白定量均明显下降 (P <0 .0 5 )。 2组临床总有效率分别是 95 .8%及 68.3 %(P <0 .0 5 )。结论 :肾康福液对慢性肾衰大鼠和病人有明显预防和治疗作用。