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1.
为筛选出特异性强、灵敏度高的犬急性肾毒性肾损伤标志物,建立急性肾毒性肾损伤模型,检测肾脏不同损伤程度下试验犬尿液和血液中4种肾损伤标志物浓度的动态变化,并通过病理学验证此变化与肾脏损伤是否具有相关性;通过血清肌酐、尿素氮检查验证此变化是否能快速、灵敏地反映肾脏损伤。结果表明,尿液中4种肾损伤标志物浓度动态变化与肾脏损伤具有良好相关性,在肾脏损伤早期浓度即开始显著升高,且时间均早于肌酐和尿素氮,因此均可作为犬急性肾毒性肾损伤早期诊断敏感标志物。血液中4种肾损伤标志物浓度动态变化与肾脏损伤具有良好相关性,其中N-乙酰-β氨基葡萄糖苷酶(NAG)和肾损伤分子(KIM-1)均在肾脏受损早期显著升高,时间均早于肌酐和尿素氮。说明NAG和KIM-1可以作为犬急性肾毒性肾损伤标志物。  相似文献   

2.
将家兔15只随机分为ARF模型Ⅰ组、ARF模型Ⅱ组和对照组.模型组每只家兔分别一次性背部皮下注射10 g/L氯化汞0,9 mL/kg和1.7 mL/kg.24 h后采集尿液和血液进行肾功能生化指标的检测,处死家兔取肾组织制片进行光镜和电镜检查.结果表明,急性肾功能衰竭的家兔血肌酐(SCr)、血清尿素氮(BUN)、半胱氨酸蛋白酶抑制剂(Cys-C)、尿微球蛋白(β2-MG)、尿微量白蛋白(MAlb)含量均升高,但尿酶变化并不显著;近曲肾小管上皮细胞变性坏死,呈现一种典型的高位肾单位肾病.  相似文献   

3.
旨在制作鸡的急性药物性肝损伤模型,将40只33日龄SPF级白羽鸡随机分成4组,每组10只,模型组灌胃不同浓度的恩诺沙星(200、150、100 mg/kg),对照组灌胃等体积蒸馏水,每天给药1次,连续给药5 d。最后1次灌胃后,禁食不禁水,24 h后空腹称重并颈静脉采血用于肝功能检测,取肝脏计算肝指数、剖检后肉眼观察、组织切片进行HE染色观察肝脏组织病理学变化。结果显示,模型组丙氨酸氨基转移酶(ALT)和直接胆红素(DBIL)同时升高,其中DBIL升高至对照组的2倍以上;总胆红素(TBIL)、碱性磷酸酶(ALP)和天冬氨酸氨基转移酶(AST)同时升高,其中TBIL升高至对照组的2倍以上,认为这2组指标可以作为恩诺沙星致鸡急性肝损伤诊断的生化参考依据;模型组肝脏病理切片均有不同程度的肝细胞病变,可视为鸡急性药物性肝损伤诊断的"金标准"。结果表明,鸡连续灌胃100 mg/kg的恩诺沙星5 d可以制作急性药物性肝损伤模型,此模型可用于保肝护肝药物筛选和药物性肝损伤机制的研究。  相似文献   

4.
为了研究麻保沙星在犬皮下给药的生物利用度,将18只犬随机分成2组,按照2mg/kg分别皮下注射或静脉注射麻保沙星后,采血待检,2周后两组交叉给药后,采血。分别在药物注射后5、10、15、30、45min,1、1.5、2,4、6,8、12、24、36、72h时采集血液。血浆通过高效液相色谱法检测药物浓度,用3P97药代动力学软件进行分析。麻保沙星皮下注射的平均药代动力学参数为:t1/2ka=0.19±0.08h;t1/2ke=7.21±1.88h;tmax=0.97±0.29h;Cmax=1.13±0.17μg/mL;AUC=13.13±4.24μg·h/mL;CL=0.17±0.05L/h;V/F=1.63±0.24L/kg。犬皮下注射麻保沙星的绝对生物利用度为66.7%,皮下注射能迅速被吸收且有较高的组织渗透性。  相似文献   

5.
旨在探讨中性粒细胞明胶酶脂质运转蛋白(NGAL)和胱抑素C(Cys-C)在药物诱导的急性肾衰竭(ARF)输液治疗过程中的变化规律和临床意义。每日皮下注射庆大霉素40mg/kg^60mg/kg建立犬的ARF模型,后静脉输注乳酸钠林格注射液。在犬ARF诱导期和恢复期,采集血清进行生化指标、NGAL和Cys-C浓度的测定,同时获取肾脏组织进行病理学分析。结果显示,在治疗过程中,犬的临床症状、尿量和尿比重都逐渐改善和恢复。血清NGAL在开始治疗后的第2天出现下降直至恢复正常,而血清Cyc-C呈现波动性的变化,血清尿素氮(BUN)和肌酐(CREA)浓度在输液第3~4天开始出现下降,但存在明显的波动性变化。组织病理学方面,肾小管细胞坏死的得到缓解和部分恢复。结果证明,乳酸钠林格注射液对庆大霉素诱导的ARF有明确的逆转作用,NGAL和Cys-C的表达规律与肾损伤的程度和肾功能变化有关,其中NGAL的表达变化对犬急性肾衰竭的早期诊断和治疗预后有很好的临床提示意义。  相似文献   

6.
为了研究腹膜透析(peritoneal dialysis,PD)治疗和输液治疗对犬急性肾损伤(acute kidney injury,AKI)的疗效,试验对8只试验犬持续皮下注射硫酸庆大霉素注射液40~60 mg/(kg·d)11 d,通过监测血液肌酐(Cr)和尿素氮(BUN)等指标的变化建立犬AKI模型,检测血液Cr、BUN、白蛋白(ALB)、磷(P)、中性粒细胞明胶酶脂质运载蛋白(NGAL)和胱抑素C(Cys C)等指标,并对比采用腹膜透析治疗和输液治疗这两种方法进行治疗时的临床症状。结果表明:Cr浓度升高超出正常水平的50%,且BUN指标呈进行性升高说明造模成功;腹膜透析治疗时各项指标的恢复均比输液治疗迅速,其中BUN、NGAL和Cys C等指标在治疗3~5 d后就与输液治疗有明显差异;与输液治疗相比,腹膜透析治疗时犬只呕吐等临床症状消失更迅速,精神、食欲迅速好转。除血液Cr、BUN等传统指标外,NGAL与Cys C这2个指标在犬AKI诊断、治疗和监测中反应更加敏感,可作为犬AKI诊断和疗效的评价指标。说明在犬AKI治疗过程中腹膜透析治疗效果明显优于输液治疗。  相似文献   

7.
急性肾损伤(acute kidney injury, AKI)目前已成为犬最主要的一种肾系疾病,尤其在老年犬中发病率逐年上升。近年来,针刺疗法在宠物临床已得到广泛的应用,并逐渐从治疗瘫痪等外科疾病向治疗宠物内科疾病的方向发展。本研究以腺嘌呤为造模药物建立急性肾损伤犬模型,采用电针疗法进行治疗。研究电针疗法对于犬的肾功能、钙磷代谢、抗氧化能力以及对于NRF2通路相关蛋白的影响,探究电针疗法对犬的急性肾损伤的治疗作用。选取24只3~4 kg健康比格犬,随机分为对照组、造模组、常规治疗组、电针干预组、电针治疗组和联合治疗组。第1~15天为造模期,第16~30天为治疗期。试验结束后检测尿比重、血清中尿素氮(BUN)、肌酐(CREA)、尿酸(UA)、钙(Ca2+)和磷(P3+)的变化;影像诊断X光检测肾变化情况;检测血清及肾组织的超氧化物歧化酶(SOD)和丙二醛(MDA);病理组织学观察各组试验犬肾组织病变的严重程度;采用qRT-PCR和Western blot方法检测各组试验犬肾组织中与抗氧化相关基因和蛋白的表达情况;用免疫组织化学的方法检测肾组织中...  相似文献   

8.
32只健康本地犬饲养1周后按体质量灌胃番泻叶水煎剂6 m L/kg人工复制脾虚泄泻证病理模型,造模成功后随机分为4组:黄芪多糖治疗组后海穴注射黄芪多糖注射液0.25 m L/kg,2次/d;硫酸庆大霉素治疗组后海穴注射硫酸庆大霉素注射液0.2 m L/kg,2次/d;后海穴针刺组后海穴注射生理盐水0.25 m L/kg,2次/d;病理对照组不作任何处理;同时设立4头健康犬作为空白对照,造模期间灌胃生理盐水。用药后治疗期间测定试验犬只的体质量、三大临床指标、部分血液指标和脾脏指数,并统计分析。结果表明,黄芪多糖治疗组血红蛋白、红细胞水平在较短时间内恢复正常,脾脏指数显著(P0.05)高于硫酸庆大霉素治疗组;硫酸庆大霉素治疗组白细胞降低速度极显著(P0.01)快于黄芪多糖治疗组。这表明后海穴注射黄芪多糖注射液可以用于治疗犬脾虚泄泻证。  相似文献   

9.
【目的】:通过测定小鼠血液中非蛋白氮(NPN)含量,确立氯化汞对小鼠急性肾损伤模型,并对肌苷和解毒净保肾作用进行比较。[方法】:16只健康昆明小鼠随机分成4组。其中A组为Hgcl损肾组;B组为Hgcl+肌苷;c组为解毒净+0.1%HgCl2及D组对照组。24h后处死采血,制备无蛋白血滤液,分别测定血液中非蛋白氮(NPN)含量,从而观察保肾药的作用。【结果]:肌苷和解毒净对氯化汞引起的急性肾损伤都有一定的保护作用。[结论]:解毒净的保肾作用优于肌苷的保肾作用。  相似文献   

10.
本研究旨在观察青蒿琥酯对庆大霉素诱导犬急性肾损伤的抗氧化调节作用及其机制。将20只犬随机等分成4组:对照组(Control)、庆大霉素模型组(GM)、青蒿琥酯治疗组(GM+ART)、青蒿琥酯+ML385干预组(GM+ART+ML385)。除对照组,其他组犬采用注射GM建立AKI模型。成功造模后,GM+ART组给与青蒿琥酯,ART+ML385组给与ART和ML385,对照组和GM组给予生理盐水,试验期12 d。用不同浓度GM与MDCK细胞共培养,确定最佳浓度为4.0 mmol·L-1,用相同方法确定ART最佳浓度为50.0 μmol·L-1。将体外培养MDCK细胞、过表达Kelch样ECH相关蛋白1(Keap1)的MDCK细胞(M-K)和敲减核因子E2相关因子2(Nrf2)表达的MDCK细胞(M-SiNrf2)分别分成3组:健康对照组、GM对照组和GM+ART干预组,共培养24 h后用于检测。结果显示:1)在动物试验中,GM+ART组肌酐(Cr)、尿素氮(UN)及肾损伤因子1(KIM-1)水平显著低于GM组,GM+ART+ML385组Cr、UN及KIM-1水平显著高于GM+ART组。2)在动物试验中,与GM组比较,GM+ART组Nrf2和谷胱甘肽半胱氨酸连接酶催化亚基(GCLC)蛋白表达上调,Keap1蛋白表达下调,肾组织匀浆中总超氧化物歧化酶(T-SOD)和谷胱甘肽(GSH)水平升高,丙二醛(MDA)水平降低。与GM+ART组比较,给与ML385后Nrf2和GCLC蛋白表达下调,T-SOD和GSH水平降低。3)在细胞试验中,与4.0 mmol·L-1 GM共培养的MDCK细胞比较,加入50.0 μmol·L-1ART能显著提高细胞增殖率,降低ROS水平,下调Keap1表达,上调Nrf2、血红素氧合酶1(HO1)及GCLC表达。4)在细胞试验中,与MDCK细胞比较,在GM+ART相同处理下,M-K细胞和M-SiNrf2细胞Keap1蛋白表达上调,Nrf2、HO1及GCLC蛋白表达下调,细胞增殖率降低,ROS含量升高(P<0.05或P<0.01)。综上所述,青蒿琥酯对庆大霉素诱导犬急性肾损伤具有保护作用,其作用机制与青蒿琥酯通过Keap1/Nrf2信号通路抑制氧化应激反应有关。  相似文献   

11.
Routinely, kidney dysfunction and decreased glomerular filtration rate (GFR) are diagnosed by the evaluation of changes in the serum creatinine (SCr) and blood urea nitrogen (BUN) concentrations. However, neither of these tests is sensitive or specific enough for the early diagnosis of impaired kidney function because they are both affected by other renal and nonrenal factors. Furthermore, kidney injury can be present in the absence of kidney dysfunction. Renal reserve enables normal GFR even when nephrons are damaged. Renal biomarkers, especially those present in urine, may be useful for the study of both acute and chronic nephropathies. The aim of this review is to describe the current status of urinary biomarkers as diagnostic tools for kidney injury in dogs with particular focus on acute kidney injury (AKI). The International Renal Interest Society (IRIS) canine AKI grading system and the implementation of urinary biomarkers in this system also are discussed. The discovery of novel urinary biomarkers has emerged from hypotheses about the pathophysiology of kidney injury, but few proteomic urine screening approaches have been described in dogs. Lack of standardization of biomarker assays further complicates the comparison of novel canine urinary biomarker validation results among studies. Future research should focus on novel biomarkers of renal origin and evaluate promising biomarkers in different clinical conditions. Validation of selected urinary biomarkers in the diagnosis of canine kidney diseases must include dogs with both renal and nonrenal diseases to evaluate their sensitivity, specificity as well as their negative and positive predictive values.  相似文献   

12.
Objective To evaluate and compare the effects of oral isosorbide and glycerol on intraocular pressure (IOP), serum osmolality (SOSM), and blood glucose (BG) in normal dogs. Methods Ten normal dogs were administered an oral dose of either isosorbide (1.5 g/kg), glycerol (1.5 g/kg) or control (water, 2 mL/kg) in a double blind protocol. Prior to dosing, baseline IOP, SOSM, and BG were measured in all dogs. IOP was subsequently evaluated every 30 min for 6 h post‐dosing. BG and SOSM were reassessed at times 1, 2, 4, and 6 h post‐dosing. After 1‐week washout periods, every dog was subject to each of the three treatments. The dogs were held NPO for 4 h after dosing. Results The maximal decrease in IOP was 17% by 1 h and 13.5% by 30 min after glycerol and isosorbide administration, respectively. However, the overall changes in IOP were not significant when compared to the controls. SOSM increased above baseline after dosing with glycerol but decreased after isosorbide, which difference was significant at 1, 2, and 4 h post‐administration. BG significantly increased after administration of glycerol relative to the control but was not significantly affected by isosorbide. Conclusions Neither glycerol nor isosorbide significantly affected IOP when compared to the control. However, glycerol induced significant elevations in both BG relative to the control and SOSM relative to isosorbide.  相似文献   

13.
The aim of our study was to investigate how the distribution and amount of cathepsin B change during acute kidney injury. The research was done on a rat model of acute kidney injury that was induced by nephrotoxic antibiotic gentamicin. Gentamicin was injected at a dose of 40 mg/kg body weight (the first treated group) and 80 mg/kg body weight (the second treated group) for 14 days. Control groups received injections of physiological saline only. One day after the last injection, animals were euthanized, dissected and kidney samples were taken and fixed in 10% buffered formalin. Tissue sections were stained with haematoxylin and eosin, periodic Acid Schiff (PAS) and Oil-red-O. Immunohistochemistry was used for the demonstration of cathepsin B. Vacuolar degeneration of the proximal convoluted tubules was the most prominent pathologic lesion found in the first treated group, while necrosis prevailed in the second treated group in the same localisation. In both treated groups significantly weaker immunohistochemical reaction for cathepsin B was noticed in the proximal convoluted tubules in comparison to the control groups (P < 0.05). The decrease of positive reaction was the largest in the proximal convoluted tubules of the outer renal cortex. Stronger positive reaction for cathepsin B, although not statistically significant, was found in the proximal straight tubules (P > 0.05), as well. However, more numerous cathepsin B-positive large granules appeared in the proximal straight tubules of the second treated group then in the second control group (P < 0.05). We can conclude that the amount of cathepsin B in the affected proximal convoluted tubules significantly decreases along the increased severity of the histopathological lesions of the proximal convoluted tubuls, the amount of enzyme in the well preserved proximal straight tubules increases and more cathepsin B-positive large granules appear in the cytoplasm.  相似文献   

14.
Renal damage, a common feature in canine leptospirosis, ranges from a subclinical affection to kidney dysfunction and death. Chances of recovery can be improved by early intervention. However, traditional biomarkers (serum urea and creatinine) have limited relevance for precocity. Kidney Injury Molecule-1 (KIM-1) is a transmembrane protein upregulated in early stages of tubular injury. This study evaluated the use of urinary KIM-1 to detect early renal injury in naturally occurring canine leptospirosis. This exploratory research included 30 dogs divided into two groups: (1) dogs with leptospirosis (n = 25) and (2) healthy dogs (n = 5). Leptospira sp. infection was diagnosed through urine PCR and/or direct bacteriologic culture and/or serology (single MAT titters ≥800). Additionally, stage of infection was further characterized in acute and subacute phases based on the onset of clinical symptoms from 3 to 7 days. Urinary KIM-1 (uKIM-1) concentrations were measured in both groups with a commercial canine ELISA kit.uKIM-1 levels were statistically different (P < 0.01) between the studied groups, especially in non-azotemic dogs (P = 0.0042). The biomarker showed 88 % sensibility to diagnosis of kidney injury at> 1.49 ng/mL cut-off. Urine KIM-1 was negatively correlated with urine specific gravity (USG) but accompanied histopathological evidence of renal degeneration, necrosis and regeneration processes, extending information on kidney health. Measurement of KIM-1 in the urine of canine patients was able to detect naturally occurring acute and subacute leptospirosis accompanied by tubular injury in early non-azotemic infections.  相似文献   

15.
Five, 3-month-old mongrel dogs weighing between 4.5 to 5.5 kg were studied to evaluate and compare the efficiency of 99mTc-DTPA, 99mTc-MAG3, and 99mTc-DMSA in detecting gentamicin-induced renal tubular injury. After baseline renograms using all three methods, all dogs received daily intramuscular injections of gentamicin at a dose of 30-45 mg/kg. Additional studies were obtained after a cumulative dose of 450, 1,575, and 2,250 mg of gentamicin was reached. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and percentage of total renal uptake measurements were calculated. Baseline and post-gentamicin injection blood urea nitrogen (BUN) and serum creatinine values were determined. A Duncan test revealed significant renal function impairment at 450 mgs of cumulated gentamicin with 99mTc-DMSA and at 1,575 mgs of cumulated gentamicin for 99mTc-DTPA and 99mTc-MAG3. There was no correlation between BUN and serum creatinine values when compared to gentamicin (p > 0.05). The images obtained with 99mTc-MAG3 were of better quality than those obtained with 99mTc-DTPA even under severe renal dysfunction. Percentage of 99mTc-DMSA uptake indicated renal damage, before than GFR and ERPF. BUN and serum creatinine measurements were poor indicators of gentamicin-induced renal failure.  相似文献   

16.
Canine leptospirosis is characterized by an acute or chronic disease. Some dogs may act as asymptomatic carriers, keeping the agent in the renal tubules and eliminating it in the urine for an extended period. Chronic kidney disease (CKD) is multifactorial and pathophysiology has been widely discussed. The aim of the study was to investigate whether the occurrence of CKD may possibly be associated with asymptomatic leptospiral infection in dogs in endemic regions. Serology and urine PCR were performed in 16 dogs with CKD and 48 healthy dogs from an endemic area. Dogs with CKD were more frequently shedders (75%) than non-CKD animals (20.8%). Therefore, our results demonstrate that asymptomatic leptospiral infection is associated with canine chronic kidney disease and that differential diagnosis is important for dogs from endemic areas presenting CKD. The early detection of shedders, besides the obvious impact on Public health may also help to improve the animal health and avoid the development of CKD.  相似文献   

17.
QUANTITATIVE CONTRAST ULTRASOUND ANALYSIS OF RENAL PERFUSION IN NORMAL DOGS   总被引:1,自引:1,他引:1  
Eight normal dogs with no evidence of renal disease, weighing between 8 and 25 kg were imaged using contrast harmonic ultrasound after injection of a microbubble contrast medium. All dogs received three separate bolus injections of 0.05 ml of commercial contrast medium (Definity). Time/mean pixel value (MPV) curves were generated for selected regions in the cortex and medulla of the left kidney in each dog. Upslope, downslope, baseline, peak intensity, and time to peak were calculated for each zone. For a bolus injection, within the renal cortex (averaging all subjects) the upslope was 7.4 +/- 1.5 MPV/s, downslope was -0.4 +/- .2 MPV/s, baseline was 66.8 +/- 9.3 MPV, peak was 103.6 +/- 8.2 MPV, time to peak (from injection) was 12.8 +/- 5.3 s and from time of contrast medium reaching the kidney was 5.1 +/- 2.0 s. Within the renal medulla (averaging all subjects), upslope was 2.8 +/- 1.7 MPV/s, downslope was -0.3 +/- .2 MPV/s, baseline was 39.3 +/- 6.0 MPV, peak was 65.2 +/- 14.3 MPV, time to peak from injection was 20.9 +/- 6.4 s and from time of contrast reaching the kidney was 11.6 +/- 4.1 s. These baseline data may prove useful in the evaluation of dogs with diffuse disease or vascular compromise.  相似文献   

18.
Three dead dogs were brought to the College of Veterinary Medicine, Kyungpook National University for study. Clinically, all the dogs showed emaciation, anorexia, depression, hemorrhagic vomiting and diarrhea for 7~10 days before death. All the clinical signs were first noted for about one month after feeding the dogs with commercial diets. At necropsy, all 3 dogs had severe renal damage with the same green-yellowish colored nephroliths in the renal pelvis. They also showed systemic hemorrhage and calcification of several organs, which might have been induced by uremia. Microscopically, necrosis, calcification and calculi were detected in the renal tubules, and especially in the proximal convoluted tubules and collecting ducts of the kidney. These findings were supportive of a mycotoxic effect, and especially on their kidneys. However, the precise cause of the toxic effect in these cases of canine renal failure could not be determined.  相似文献   

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