慢性肾功能衰竭大鼠模型的建立与评价

建立两种慢性肾功能衰竭CRF动物模型:(1)大鼠肾大部分切除诱发肾衰(Platt法);(2)腺嘌呤诱发大鼠慢性肾功能衰竭的动物模型(Yokozawa法)。分别测定血清中血尿素氮(BUN),血肌酐(Scr)Ca2+、P5+等含量。取肾脏组织,HE染色,观察两种慢性肾功能衰竭大鼠模型肾脏组织的损伤情况。结果模型组大鼠血清中血尿素氮(BUN)、血肌酐(Scr)等含量明显升高,HE染色显示两种模型大鼠肾脏组织不同程度的损伤。通过对两种制备方法的可行性和操作性、制备原理、病变特点以及模型应用范围的对比,寻找建立接近临床实际,适用广泛,统一、简便、稳定的CRF动物模型。制作符合人类CRF的动物模型,对研究CRF的发病机理,探讨组织形态的变化与生化指标及临床表现的相互关系,筛选有效药物,阐明疗效机制均有重要作用。     

氯化汞诱导比格犬急性肾功能衰竭模型的建立

为了探讨氯化汞诱导比格犬急性肾功能衰竭模型的建立方法,试验选取14只比格犬随机分成2 mg/kg组(A组)、4 mg/kg组(B组),并设立生理盐水对照组,连续注射7 d,注射氯化汞后的第1~3周测定试验犬的肝脏、肾脏功能及观察相关脏器病理变化。结果表明:梯度剂量氯化汞可诱发比格犬不同程度的急性肾功能衰竭,但B组存在较严重的多器官损害。采用A组的方法,即每千克体重以2.0 mg的剂量连续注射7 d氯化汞溶液可建立急性肾功能衰竭模型。     

发酵驼乳和发酵牛乳对慢性肾功能衰竭大鼠影响的比较研究

为了研究发酵驼乳和发酵牛乳对腺嘌呤所致大鼠慢性肾功能衰竭的影响效果。试验采用腺嘌呤复制慢性肾功能衰竭大鼠模型,以发酵驼乳和发酵牛乳作为受试物进行灌胃干预。通过检测大鼠体质量、血肌酐（Scr）、尿素氮（BUN）、一氧化氮（NO）、超氧化物歧化酶（SOD）、血清总蛋白（TP）、钙（Ca）、磷（P）、24 h尿量、尿蛋白（UP）及肾脏病理组织学变化,分析驼乳对慢性肾功能衰竭大鼠的影响。结果：发酵驼乳可降低大鼠Scr、BUN水平、减缓UP、调节Ca、P的含量,提高SOD、TP水平,具有保护肾功能的作用。结论：驼乳对慢性肾功能衰竭大鼠的病情起到缓解作用。     

益生菌发酵驼乳对慢性肾功能衰竭的治疗作用

目的：比较不同菌种发酵的驼乳制品对腺嘌呤所致大鼠慢性。肾功能衰竭（CRF）的缓解作用。方法：采用腺嘌呤复制CRF大鼠模型,以不同发酵剂发酵的驼乳作为受试物进行灌胃干预。通过检测大鼠的饮食饮水情况、排尿量、尿液和血清常规指标及肾脏病理组织学变化,评估各发酵驼乳对CRF大鼠的治疗效果。结果：发酵驼乳均可改善肾功能衰竭大鼠的一般生理状况,可降低大鼠血肌酐（Scr）、尿素氦（BUN）水平,减缓尿蛋白（UP）,调节Ca、P的含量,提高过氧化物歧化酶（SOD）、血清总蛋白（STP）水平,具有保护肾功能的作用,其中LIcaseiZhang发酵的驼乳对CRF大鼠的改善效果最佳。     

鸭油甘油二酯对肥胖大鼠减肥降脂作用与机制研究

本试验旨在研究鸭油、鸭油甘油二酯对肥胖大鼠体重、器官指数、血清生化指标的影响,以及鸭油甘油二酯抗肥胖和降胆固醇作用的潜在机制。试验分为2个阶段。造模阶段：将80只大鼠随机分为2个组,对照组每组4个重复,每个重复5只;造模组每组12个重复,每个重复5只。对照组大鼠自由采食基础饲粮,造模组大鼠自由采食脂肪含量为60%的高脂饲粮,连续饲养28 d。修复干预阶段：将造模组的肥胖大鼠随机分为模型对照组、鸭油组、鸭油甘油二酯组,每组4个重复,每个重复5只。模型对照组以蒸馏水灌胃,用高脂饲粮连续喂养30 d,其余各组分别用鸭油、鸭油甘油二酯进行灌胃,用基础饲粮连续喂养30 d。结果表明：1）与对照组相比,造模组的体重显著升高（P<0.05）,表明造模成功。2）与模型对照组相比,鸭油甘油二酯组的最终体重、Lee’s指数、肝体比以及血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇含量均显著降低（P<0.05）;血清高密度脂蛋白胆固醇含量升高,但差异不显著（P>0.05）;心体比、脾体比、肾体比、睾体比均无显著差异（P>0.05）。3）与模型对照组相比,鸭油甘油二酯组的肝脏甘油三酯、磷脂...     

纳米硒对犬肾衰中肾组织离子转运体表达及凋亡的影响

旨在探究纳米硒作为治疗药物对腺嘌呤诱导急性肾衰犬肾组织离子转运体表达及凋亡的影响。20只体重约4 kg年龄1岁左右的贵宾犬在做基本健康检查并适应性喂养两周后,随机分为空白对照组(Control,饲喂基础日粮30 d)、急性肾衰造模组[Model,15 d基础日粮+15 d腺嘌呤75 mg·(kg·d)^-1]、常规输液治疗组[Infusion,15 d腺嘌呤75 mg·(kg·d)^-1+15 d静注葡萄糖氯化钠60 mL·(kg·d)^-1、呋塞米2~4 mg·kg^-1]、纳米硒治疗组[Nano-Se,15 d腺嘌呤,75 mg·(kg·d)^-1+15 d纳米硒0.5 mg·(kg·d)^-1]、纳米硒预防组[Prevention,15 d纳米硒0.5 mg·(kg·d)^-1+15 d腺嘌呤75 mg·(kg·d)^-1],每组4只犬。通过血液生化分析,尿常规分析,肾组织石蜡切片免疫组化,Western blot,RT-qPCR检测相关蛋白基因表达水平。结果表明：纳米硒治疗与预防有效降低肾衰特征指标CRE、BUN,恢复肾衰异常尿常规指标尿比重、尿pH,改善肾衰犬机体钙磷代谢;纳米硒治疗对比急性肾衰造模组可有效增加肾组织CaSR、WNKs mRNA与蛋白表达量(P<0.05),降低NKCC2 mRNA与蛋白表达量(P<0.05),从而减弱了急性肾衰中过度代偿的重吸收功能;纳米硒治疗较肾衰造模组肾组织促凋亡Bax、Caspase3/9 mRNA与蛋白表达量显著下调(P<0.05),降低急性肾衰中肾的凋亡效应。     

电针百会穴对脾虚泄泻模型大鼠影响的研究

旨在探讨电针百会穴对脾虚泄泻大鼠的影响.选取64只Wistar大鼠,分成假手术组、模型组、百会组和阳性对照组.除假手术组外,其他各造模组以灌胃番泻叶浸液造模,待造模组出现脾虚泄泻症状后,百会组电针百会穴,阳性对照组灌胃蒙脱石散,持续2周.整个试验过程中观察并记录所有大鼠的症状体征、体质量和腹泻指数.试验结束后,检测各组...     

饲料中不同蛋白和钙对鸡肾脏影响的研究

通过饲喂不同蛋白,人工试验出鸡尿酸盐沉积模型,并观察鸡肾脏临床病理变化。采用高蛋白高钙饲料造模,将动物分健康对照组、高蛋白组、高钙组、高蛋白高钙组,通过鸡的死亡率、采食饮水量的变化、体重变化率、血液中尿酸盐含量等指标,考察肾肿模型,其中用磷钨酸显色法测定鸡血液中尿酸的含量。高蛋白高钙能使鸡增重率降低,鸡的饮水量、采食量降低,死亡率升高,血清中尿酸盐含量升高,尿酸盐在肾脏沉积形成花斑肾。用44%高蛋白高钙(0.5%钙)可以人工试验出鸡尿酸盐沉积模型。     

驼乳对大白鼠肾病模型组织结构的影响

采用组织切片方法对50只大白鼠进行了实验。按每个实验组平均体重最相近原则分为正常对照组、病理模型组、尿毒清干预组、驼乳低剂量组、驼乳高剂量组5个组,每组10只,进行为期7d的适应性饲养后, 从实验的第1天开始除正常对照组外, 其他组用腺嘌呤蒸馏水配制成浓度为 2%的混悬液, 大白鼠按200 mg/d 剂量,灌胃给药确定建立慢性肾功能衰竭模型。同时,每日15:00尿毒清干预组灌胃 25%尿毒清溶液,驼乳低剂量组、驼乳高剂量组灌予驼乳,每日1次,共28 d。停药后将大白鼠致死,取肾脏组织,制作组织切片,显微观察。结果表明,病理模型组肾小球无明显变化,肾小管及间质内有大量的中性粒细胞,部分肾小管破坏、萎缩,其中可见淋巴细胞浸润及结缔组织增生、部分肾小管扩张、肾小管上皮细胞明显增生;尿毒清干预组基本病变与投药组基本一致,但肾小管的破坏程度有所减少;驼乳低剂量组和驼乳高剂量组的病变基本与投药组相同。     

高脂血症大鼠模型4种造模方法的筛选及优化

通过不同的造模方法诱导高脂血症大鼠模型,筛选出理想的高脂血症造模方法.将50只大鼠随机分为空白组、模型组Ⅰ、模型组Ⅱ、模型组Ⅲ、模型组Ⅳ,每组10只.各模型组分别采用不同造模方法诱导高脂血症大鼠模型,模型组Ⅰ:基础饲料85 g+猪油15 g;模型组Ⅱ:基础饲料63 g+猪油15 g+蛋黄粉10 g+蔗糖10 g+胆固醇2 g;模型组Ⅲ:基础饲料60.8 g+猪油15 g+蛋黄粉10 g+蔗糖10 g+胆固醇2 g+胆酸钠2 g+丙基硫氧嘧啶0.2g;模型组Ⅳ:一次性腹腔注射维生素D3600 000 U/kg后,饲养方法同模型组Ⅲ.造模第3周末、第8周末于大鼠眼眶静脉丛取血,提取血清,以ELISA法检测血清中总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)的水平.结果表明,模型组Ⅲ和模型组Ⅳ均出现血脂代谢紊乱,高脂血症模型构建成功,且模型组Ⅳ造模周期明显较模型组Ⅲ缩短,节约试验成本,所造模型可以稳定保持5周以上.模型Ⅳ方法是建立高脂血症大鼠模型的理想方法.     

中兽医古方治疗肾阳虚证部分研究进展

摘要：肾阳虚证为命门火衰,温煦失常,气化不利所致的一种虚寒性证候,肾阳虚证在家畜生产实践中常见,影响其生产效能。治疗方剂层出不群,传统古方五子衍宗丸、补肾宁、肾气丸和右归丸等是常用基础方,在此基础上结合辨证施治方法衍生的自拟处方不在少数。对诸多方剂适用证候、治疗效果进行总结概括,指导兽医人员临床用药。结果表明：催情散多用于肾阳虚引起的公畜少精、弱精证,以及母畜卵巢发育不全等繁殖障碍性疾病;肾气丸与右归丸多用于改善公畜生殖系统,提高精子活力;补肾宁可促进母畜排卵,五子衍宗丸能抑制生殖系统炎症因子,降低生殖道炎症的发生率。     

电针疗法对AKI犬的肾功能、钙磷代谢、抗氧化能力以及NRF2信号通路的影响

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...     

破格救心汤对心衰大鼠血小板膜糖蛋白ⅡbⅢa浓度的影响

研究破格救心汤对慢性心力衰竭(CHF)大鼠血小板膜糖蛋白ⅡbⅢa(GP-ⅡbⅢa)浓度的影响,探讨其治疗CHF的作用机制。采用阿霉素诱导法复制CHF大鼠模型,随机分为空白组、模型组和破格救心汤组。记录各组大鼠死亡情况和一般情况,并运用ELISA试剂盒检测各组大鼠的GP-ⅡbⅢa浓度。模型组大鼠死亡4只,破格救心汤组和空白组无死亡。模型组大鼠出现鼻唇紫绀、四肢末梢苍白、被毛粗糙变黄、进食减少、行动缓慢等。与模型组比较,破格救心汤组大鼠症状明显减轻,GP-ⅡbⅢa浓度明显降低(P<0.01)。破格救心汤能降低心衰大鼠GP-ⅡbⅢa浓度,减少血栓栓塞性疾病的发生率,这可能是其治疗CHF的作用机制之一。     

Urinary alkaline phosphatase and 7-glutamyl transferase as indicators of acute renal damage in dogs

Urinary alkaline phosphatase (AP) and 7-glutamyl transferase (GGT) levels were measured in normal dogs, dogs with chronic renal failure, and dogs with acute renal failure, as confirmed by renal histology. The median values for urinary AP were 5–8 iu/litre/mmol creatinine for normal dogs, 6–7 for dogs with chronic renal failure and 49-4 for dogs with acute renal failure. The median values for urinary GGT were 3–4 iu/litre/mmol creatinine for normal dogs, 4–9 for dogs with chronic renal failure and 9-6 for dogs with acute renal failure. The results suggest that urinary AP can be used as an indicator of acute renal damage in the dog. GGT was shown to be less useful. No clear correlations were found between urinary enzyme levels and the extent of morphological kidney damage.     

大鼠慢性心力衰竭模型心电图分析

为探讨大鼠心电图(ECG)在评价大鼠慢性心力衰竭(CHF)模型中的意义,以SD大鼠36只随机分为2组,模型组24只,正常组12只.模型组采用阿霉素诱导法复制CHF大鼠模型.记录标准肢体Ⅱ导联ECG,并用心脏系数和心肌病理学检查验证.结果显示,模型组大鼠ECG典型改变为ST段凸面向上抬高(电压约升高0.12mV)和T波高...     

Chronic renal failure in an English bull terrier with polycystic kidney disease

An entire female English bull terrier, aged five years and one month, was diagnosed with polycystic kidney disease by renal ultrasonography. It had thickening and abnormal motion of the mitral valve on 2D and M mode echocardiography, and left ventricular outflow tract obstruction, characterised by turbulence in the left ventricular outflow tract and elevated aortic blood flow velocity, detected by colour flow and spectral Doppler echocardiography, respectively. Two years later, haematology, serum biochemistry and urinalysis data suggested the presence of compensated renal failure. The dog was euthanased at 10 years and eight months of age, with haematology, serum biochemistry and urinalysis data Indicating decompensated chronic renal failure. Postmortem examination confirmed polycystic kidney disease, chronic renal disease, mitral and aortic valvular myxomatous degeneration, and mixed mammary neoplasia. This case demonstrates that bull terriers with polycystic kidney disease may develop associated chronic renal failure.     

Renal microcirculatory and correlated histologic changes associated with dirofilariasis in dogs

Nine 7-month-old Beagle dogs were inoculated with 200 third-stage larvae of Dirofilaria immitis. The development of cardiac disease secondary to heartworm infection was confirmed by thoracic radiography, echocardiography, and angiography with blood pressure measurements. The only indication of renal disease was mild-to-moderate proteinuria. The dogs were euthanatized approximately 18 months after inoculation. The mean microfilarial count in blood at the time of euthanasia was 88,700/ml, with a mean of 89 adult heartworms in the vena cavae, heart, and pulmonary arteries. The kidneys were perfused for microangiographic and correlative histologic examination of the intrarenal microvasculature and associated renal morphologic features. Angiograms of whole kidneys from 6 dogs revealed attenuation or truncation of the major renal vessels. Microangiograms of all kidney slices revealed attenuation in the microangiographic appearance of the glomerular capillaries. Histologic examination of all kidney slices revealed mild-to-intense, diffuse, chronic interstitial nephritis and generalized membranoproliferative glomerulonephritis. Microfilariae were observed within the glomerular capillaries and the medullary vessels. The microangiographic changes correlated with and were explained in part by the histologic changes in the renal parenchyma.     

Evaluation of cystatin C as an endogenous marker of glomerular filtration rate in dogs

Cystatin C is a cysteine protease inhibitor produced by all nucleated cells. It is freely filtered by the glomerulus and is unaffected by nonrenal factors such as inflammation and gender. Because of greater sensitivity and specificity, cystatin C has been proposed to replace creatinine as a marker of glomerular filtration rate (GFR) in humans. The aims of this study were to validate an automated assay in canine plasma and to evaluate the usefulness of cystatin C as a marker of GFR in dogs. Western blotting was used to demonstrate cross-reactivity of an anti-human cystatin C antibody. An immunoturbidimetric assay was used to detect cystatin C in 25 clinically healthy dogs and 25 dogs with renal failure. Mean cystatin C concentration in the healthy dogs and the dogs with renal failure was 1.08 +/- 0.16 mg/L and 4.37 +/- 1.79 mg/L respectively. Intra- and interassay variability was <5%. The assay was linear (r = .974) between 0.14 and 7.53 mg/L. Both cystatin C and creatinine concentrations were measured in banked, frozen serum from 20 remnant kidney model dogs and 10 volume-depleted dogs for which GFR measurements by exogenous creatinine clearance had been determined previously. In the remnant kidney model, cystatin C was better correlated with GFR than creatinine (r = .79 versus .54) but was less well correlated with GFR in volume-depleted dogs (r = .54 versus .95). GFR measurements were repeated in the remnant kidney model dogs 60 days after initial GFR measurements. At this time, cystatin C and creatinine concentrations correlated equally well with GFR (r = .891 versus .894, respectively). Cystatin C concentration is a reasonable alternative to creatinine for screening dogs with decreased GFR due to chronic renal failure.     

2型糖尿病合并肾性高血压模型的建立及评价

制备一种发病过程类似于人类2型糖尿病合并肾性高血压疾病的大鼠模型。大鼠高脂高糖膳食4周后,予快速腹腔注射链脲佐菌素(STZ)溶液28mg/kg,制作成2型糖尿病模型。2周后,连续3d均测得空腹血糖(FBG)≥7.8mmoL/L或随机血糖(RBG)≥16.7mmol/L,为2型糖尿病成模标准。待血糖稳定后,再用改良的"两肾一夹法"结扎肾动脉,造成一侧肾动脉狭窄,形成肾性高血压。2周后,连续3d均测得大鼠收缩压(SBP)≥140mmHg,同时FBG≥7.8mmol/L或RBG≥16.7mmol/L,确定为2型糖尿病合并肾性高血压模型制作成功。4周后,模型大鼠血糖、血压稳定。与空白对照组相比,复合模型组大鼠出现体重减轻、空腹血糖升高、糖化血红蛋白值升高(P0.01),血压升高(P0.01);与糖尿病组和假手术组相比,复合模型组大鼠血肌酐,尿素氮变化不明显(P0.05),但血压明显升高(P0.01);同时,彩超结果显示,复合模型组大鼠左侧肾脏、肾动脉直径均变小,血流速增快。大鼠高脂高糖膳食后,用低剂量链脲佐菌素(STZ)溶液腹腔注射,再用改良的"二肾一夹"法制备的2型糖尿病合并肾性高血压大鼠模型,在一定程度上较好地模拟出该疾病的发病特点,可为2型糖尿病合并肾性高血压后的临床及试验研究提供一个稳定、实用、有效的新模型。