本文選題：阿霉素腎病兔 + 蛋白尿　； 參考：《安徽醫(yī)科大學(xué)》2014年碩士論文

【摘要】：研究目的 觀察單側(cè)腎切除阿霉素腎病兔ApoB mRNA編輯效率及其血、尿液生化和腎臟病理學(xué)改變。 研究資料與方法 40只雄性6月齡新西蘭兔，體重1000±100g，隨機(jī)分為病例組（n=20只）、假手術(shù)組（n=20只）。①病例組：以3%的戊巴比妥30mg/Kg行腹腔注射麻醉，無菌條件下行左腎切除，1w后耳靜脈注射阿霉素5mg/Kg，術(shù)后12周處死所有兔子留取腎臟及肝臟標(biāo)本，濾紙吸干后稱重，立即用10%中性福爾馬林溶液固定，石蠟包埋；②假手術(shù)組：以3%的戊巴比妥30mg/Kg行腹腔注射麻醉，只探及腎包膜不切除左腎，1w后耳靜脈注射生理鹽水5mg/Kg，術(shù)后12周處死所有兔子留取腎臟標(biāo)本，濾紙吸干后稱重，立即用10%中性福爾馬林溶液固定，石蠟包埋。另分別于試驗前（0周）和試驗結(jié)束（12周）檢測血清肌酐(Scr)、尿素氮(BUN)、總蛋白(TP)、白蛋白(Alb)、24h尿蛋白(24h UPr)及載脂蛋白B-100、載脂蛋白B-48。酶法測定Scr、BUN、TP、Alb；放射免疫法檢測血漿ApoB-100、ApoB-48；雙縮脲比色法檢測24小時尿蛋白濃度；蘇木素一伊紅(HE)染色觀察腎臟病理改變；免疫組化觀測肝臟ApoB-100及ApoB-48的組織表達(dá)。 研究結(jié)果 ①病例組24h UPr和血清Scr、BUN、ApoB-100和ApoB-48顯著高于假手術(shù)組，而血清TP，Alb則明顯降低。 ②病例組腎臟腎臟腎上皮細(xì)胞腫脹，系膜細(xì)胞增生、系膜基質(zhì)增多；腎間質(zhì)增寬，，可見大量炎癥細(xì)胞浸潤。ApoB-100和ApoB-48以腎小球表達(dá)增高為主。 研究結(jié)論 單側(cè)腎切除加1周后耳靜脈注射阿霉素(5mg／kg)在術(shù)后12周可以成功建立腎病模型，具體表現(xiàn)為大量蛋白尿、低蛋白血癥和明顯的高脂血癥，腎臟病理顯示局灶性病變及肝臟組織ApoB-100和ApoB-48表達(dá)普遍增高。 研究目的 觀察外源性Apobec-1基因?qū)胄挛魈m兔體內(nèi)后，肝臟apoB mRNA編輯效率及其對血脂代謝的影響。 研究資料與方法 60只雄性6月齡新西蘭兔，體重1000±100g，隨機(jī)分為apobec-1腺病毒感染病例組（n=20）、假干預(yù)組（n=20)，假手術(shù)組（n=20)，置于代謝籠中飼養(yǎng)。①病例組：以3%的戊巴比妥30mg/Kg行腹腔注射麻醉，無菌條件下行左腎切除，1w后耳靜脈注射阿霉素5mg/Kg，術(shù)后11周處死每組的半數(shù)兔子留取肝臟標(biāo)本，其余兔子分別通過耳緣靜脈注入Apobec-1重組腺病毒，飼養(yǎng)1周，摘除右側(cè)腎臟和肝臟，濾紙吸干后稱重，立即用10%中性福爾馬林溶液固定，石蠟包埋；②假干預(yù)組：以3%的戊巴比妥30mg/Kg行腹腔注射麻醉，無菌條件下行左腎切除，1w后耳靜脈注射阿霉素5mg/Kg，術(shù)后11周處死每組的半數(shù)兔子留取肝臟標(biāo)本，其余兔子分別通過耳緣靜脈注入空白腺病毒，飼養(yǎng)1周，摘除右側(cè)腎臟和肝臟，濾紙吸干后稱重，立即用10%中性福爾馬林溶液固定，石蠟包埋；③假手術(shù)組：以3%的戊巴比妥30mg/Kg行腹腔注射麻醉，只探及腎包膜不切除左腎，1w后耳靜脈注射生理鹽水5mg/Kg，術(shù)后11周處死每組的半數(shù)兔子留取肝臟標(biāo)本，其余兔子分別通過耳緣靜脈注入Apobec-1重組腺病毒，飼養(yǎng)1周，摘除右側(cè)腎臟和肝臟，濾紙吸干后稱重，立即用10%中性福爾馬林溶液固定，石蠟包埋。分別留取處死前后靜脈血及24h尿液。 研究結(jié)果 ①用藥前病例組24h UPr、ApoB-100和ApoB-48、TG及TCH、VLDL、LDL-C顯著高于假手術(shù)組，而與假干預(yù)組相差不大，而用藥后24小時病例組尿蛋白較前有所緩解，ApoB-100、TG及TCH、VLDL、LDL-C顯著下降，TP明顯升高，ApoB-48上升不明顯，假干預(yù)組及假手術(shù)組用藥后改變與用藥前差別不大。②導(dǎo)入重組腺病毒前后肝臟病理未發(fā)現(xiàn)有畸形改變；③Western Blot均顯示病例組肝臟組織顯著表達(dá)Apobec-1和ApoB-48。 研究結(jié)論 Apobec-1重組腺病毒導(dǎo)入可在一定程度上起到降血脂和腎臟保護(hù)效應(yīng)，尚未發(fā)現(xiàn)明顯肝臟致畸改變。
[Abstract]:research objective
Objective To observe the editing efficiency of ApoB mRNA in unilateral nephrectomy rabbits with adriamycin nephropathy and their changes in blood, urine biochemistry and renal pathology.
Research materials and methods
40 male 6 month old New Zealand rabbits, weighing 1000 + 100g, were randomly divided into case group (n=20) and sham operation group (n=20 only). (1) case group: intraperitoneal injection of 3% pentobarbital 30mg/Kg, left nephrectomy under aseptic conditions, and adriamycin 5mg/Kg after 1W, all rabbits were sacrificed for kidney and liver specimens for 12 weeks after 12 weeks of operation and filter paper sucked. After dry weighing, immediately fixed with 10% neutral formalin solution, paraffin embedded; sham operation group: intraperitoneal injection of 3% pentobarbital 30mg/Kg, only the renal capsule did not remove the left kidney, 1W posterior auricular vein injection of saline 5mg/Kg, 12 weeks after the operation, all rabbits were left to take the kidney specimen, filter paper was weighed after sucking dry, immediately use 10% neutrality Faure Marin solution was fixed and paraffin was embedded. The serum creatinine (Scr), urea nitrogen (BUN), total protein (TP), albumin (Alb), 24h urine protein (24h UPr) and apolipoprotein B-100 were detected before the test (0 weeks) and the end of the experiment (12 weeks). The apolipoprotein B-48. enzyme method was used to determine Scr, BUN, TP, and arsenic. The urine protein concentration of 24 hours was measured by colorimetric method. The pathological changes of kidney were observed by hematoxylin and eosin (HE) staining, and the tissue expression of liver ApoB-100 and ApoB-48 was observed by immunohistochemistry.
Research results
(1) 24h UPr and serum Scr, BUN, ApoB-100 and ApoB-48 in case group were significantly higher than those in sham operation group, while serum TP and Alb decreased significantly.
In case group, renal renal epithelial cells were swollen, mesangial cells proliferated, mesangial matrix increased, renal interstitium widened, and a large number of inflammatory cells infiltrated.ApoB-100 and ApoB-48 with increased glomerular expression.
research conclusion
A nephrotic model could be successfully established at 12 weeks after unilateral nephrectomy plus adriamycin injection (5mg / kg) after 1 weeks. The specific manifestations were a large number of proteinuria, hypoproteinemia and obvious hyperlipidemia. The renal pathological manifestations of focal lesions and liver tissue ApoB-100 and ApoB-48 were generally increased.
research objective
To observe the apoB mRNA editing efficiency and the effect on lipid metabolism in the liver of New Zealand rabbits after the introduction of exogenous Apobec-1 gene.
Research materials and methods
60 male 6 month old New Zealand rabbits, weighing 1000 + 100g, were randomly divided into apobec-1 adenovirus infection case group (n=20), false intervention group (n=20), sham operation group (n=20) and kept in metabolic cage. (1) case group: intraperitoneal injection of 3% pentobarbital 30mg/Kg, left nephrectomy under no bacteria condition, and adriamycin 5mg/Kg after 1W, after 1W. Half of the rabbits in each group were sacrificed for 11 weeks to leave the liver specimens. The rest of the rabbits were injected with Apobec-1 recombinant adenovirus through the auricular vein. The right kidney and liver were removed for 1 weeks. The filter paper was removed and weighed after sucking the filter paper. 10% neutral Faure Marin solution was fixed and paraffin embedded. 2. The false intervention group was injected with 3% pentobarbital 30mg/Kg. Left nephrectomy under sterile conditions and adriamycin 5mg/Kg were injected into the auricular vein after 1W. Half of the rabbits in each group were sacrificed 11 weeks after the operation to leave the liver specimens. The rest of the rabbits were injected with the blank adenovirus through the ear vein. The right kidney and liver were removed for 1 weeks. The filter paper was weighed after sucking the filter paper. 10% neutral formalin solution was immediately fixed and paraffin paraffin was used. Buried; (3) sham operation group: intraperitoneal injection of 3% pentobarbital 30mg/Kg, only the renal capsule did not remove the left kidney, 1W posterior auricular vein injection of saline 5mg/Kg, 11 weeks after the operation, half of the rabbits in each group were sacrificed to leave the liver specimens, and the rest of the rabbits were injected with the Apobec-1 recombinant adenovirus through the ear vein, and the right kidney was removed for 1 weeks. After weighing with the liver, the filter paper was dried and weighed immediately. 10% neutral formalin solution was fixed and paraffin embedded. The venous blood and 24h urine were collected before and after the death.
Research results
(1) 24h UPr, ApoB-100 and ApoB-48, TG and TCH, VLDL, and LDL-C were significantly higher than those in the sham operation group, but the urine protein in the case group was significantly different from that in the sham intervention group, while the 24 hours after the drug use was relieved, ApoB-100, TG and TCH, VLDL, increased significantly. There was not much difference between the changes before and before the drug use. (2) there was no abnormal change in the liver pathology before and after the introduction of the recombinant adenovirus; (3) Western Blot showed that the liver tissues of the case group showed significant expression of Apobec-1 and ApoB-48.
research conclusion
Apobec-1 recombinant adenovirus can play a role in lowering blood lipid and renal protection to some extent, and has not found obvious liver teratogenic changes.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R699.2

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