【文章內容簡介】
射或腹腔內注射,給藥劑量80 mg~400 ml/d),用藥時間414 d,觀察到停藥后30 d出現(xiàn)腎問質纖維化。,Wistar大鼠連續(xù)2 d皮下注射慶大霉素250 mg/(kg /d),觀察到4 d時腎問質纖維化最明顯,28 d時恢復正常。,第四十一頁,共八十三頁。,3.6.鎮(zhèn)痛藥腎病(sh232。n b236。nɡ)動物模型,用雌性Fischer 344大鼠,阿司匹林230 m∥(kgd)和撲熱息痛380 m∥(kgd)溶解于飲水,持續(xù)給藥65周。最早出現(xiàn)(chūxi224。n)腎乳頭的結構損傷,并累及腎間質細胞和基質,隨后可見到腎間質纖維化和腎小管萎縮。,3.7.蛋白(d224。nb225。i)超負荷引起的腎間質纖維化動物模型,大鼠和小鼠建立的每日腹腔注射無菌小牛血清0.5 mL,造成腎間質纖維化的同時還造成明顯的腎小球硬化。,第四十二頁,共八十三頁。,3.8.ETl轉基因小鼠腎纖維化動物模型,將人的ET1基因通過顯微注射法轉移到NMRI小鼠受精卵,ET1在腎、腦和肺高表達。此轉基因小鼠在14個月時觀察(guānch225。)到腎小球硬化、腎間質纖維化和’腎囊腫,而無高血壓,提示ETl能非血壓依賴地引起腎纖維化。此ET1轉基因小鼠未出現(xiàn)明顯蛋白尿。,第四十三頁,共八十三頁。,四、腎衰動物模型,急性腎衰竭(acute renal failure,ARF)是指由于(y243。uy)各種原因引起的腎功能急劇下降的臨床綜合癥。,1.油酸誘發(fā)的大鼠急性腎衰模型(m243。x237。ng) 2.缺血性急性腎衰動物模型 3.汞劑誘發(fā)家兔急性腎衰模型 4.氨基糖甙類抗生素誘發(fā)大鼠急性腎衰模型,第四十四頁,共八十三頁。,4.1.油酸誘發(fā)的大鼠急性(j237。x236。ng)腎衰模型,第四十五頁,共八十三頁。,【模型(m243。x237。ng)特點】,第四十六頁,共八十三頁。,4.2Mouse model of ischemic acute kidney injury,Experimental Procedures for Bilateral Ischemic AKI in Mice,1.Preparation for experiment,homeothermic monitor system, animal hair clipper , tissue forceps with blunt points, tweezers with ultrasharp points, dissecting and operating scissors with sharp points , microaneurysm clip applying forceps, 4–0 Vicryl suture with 1/2circle needle of 17mm length。 needle holder, Michel wound clips, Michel wound clipapplying forceps, 1ml syringes, 30 G needles, alcohol swab, cotton swab, gauze sponges, and surgical gloves. 0.9% sodium chloride), 5 mg/ml pentobarbital in saline, 0.03 mg/ml buprenorphine in saline,第四十七頁,共八十三頁。,2. Surgical procedure and surgery,Fig. 1. Sites of ?ank incision of bilateral mouse model of ischemic acute kidney injury (AKI). The incision sites on the left (A) and right (B) sides are labeled with red line.,第四十八頁,共八十三頁。,3.Monitoring the Success of Renal IschemiaReperfusion,1. The kidney color,Red dark purple deep dark purple change back to red,Remove the clips,2. Blood urea nitrogen (BUN) and serum creatinine detection,Monitor the BUN before the renal ischemia and at different reperfusion time points.,The serum creatinine is usually determined at the endpoint of the experiment,3. Histological examination of kidney tissues,第四十九頁,共八十三頁。,Fig2 Blood urea nitrogen (BUN) level of C57BL/6 mice after different ischemiareperfusion periods.,第五十頁,共八十三頁。,Fig 3 Histological examination of kidney tissues by methods such as hematoxylinandeosin (Hamp。E),第五十一頁,共八十三頁。,4. How to create a consistent mouse model of Ischemic AKI,1.Mouse surgeon.,2. Animals. animal age, sex, genetic background,3.Key Equipment。 microaneurysm clips,4.Surgery: (1)Dehydration status and surgery time: conduct the ischemia experiment at a certain time of the day,第五十二頁,共八十三頁。,