兰州大学机构库 >学院待认领
苦参碱对阿霉素诱导大鼠肾损害的保护作用及对Podocin、α-actinin-4的影响
Alternative TitleThe Effect of Matrine in the Adriamycin-induced Nephropathy Rats and the Expression of Podocin and α-actinin-4
刘亮亮
Thesis Advisor李宇宁
2015-05-17
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword苦参碱 阿霉素 肾小球硬化 podocin α-actinin-4
Abstract目的:1.观察苦参碱对阿霉素大鼠肾脏病模型的肾小球损害干预效果;2.研究苦参碱对阿霉素大鼠肾损害模型中足细胞蛋白podocin、α-actinin-4的表达变化。 方法:对SPF级健康雄性大鼠进行分组,左侧肾脏切除术后适应性喂养一周,分2次、2周予大鼠经尾静脉给adriamycin各5毫克/千克、2.5毫克/千克,成功建立阿霉素大鼠肾损害病理模型。其中大鼠分组为:空白对照组(A)、假手术组(B)、模型组(C)、干预组1(25毫克/千克·天)(D)、干预组2(50毫克/千克·天)(E)。于建立模型完成第2、4、6周测定每组大鼠24小时尿蛋白,于6周时取肾皮质行病理切片观察(光、电镜),评估肾小球硬化程度,Western-Blot检测肾组织中Podocin、α-actinin-4的表达。 结果:1.对照组和假手术相对比,同时间点24小时尿蛋白水平、病理切片观察均无显著不同。2.模型组与空白组相较之下,切片检查行HE、PAS、Masson染色于光镜下可见模型组呈弥漫性肾小球节段性硬化,周围血管腔扩张,小管间质广泛纤维化。电镜下足细胞的足突消失融合,基底膜增厚不规则,小管上皮细胞微绒毛脱落、消失,内皮细胞肿胀。数据显示模型组和对照组相较,24小时尿蛋白水平大幅升高;病理切片观察肾小球硬化程度比对照大鼠损害更显著(P<0.05)。Western-Blot 结果显示模型组Podocin、α-actinin-4蛋白于6周末表达降低(P<0.05)。3.苦参碱干预后,与模型组比较,小剂量干预组、大剂量干预组HE、PAS、Masson染色光镜下可见肾小球硬化,基底膜变厚,系膜细胞明显增生,病变比模型组明显轻微。电镜观察皮质标本示足突绒毛化、轻度融合,少量纤维增生,病变比模型组轻微;24小时尿蛋白在2周比模型组高,4周水平开始下降,比模型组低,仍比对照组高(P<0.05),6周时蛋白持续下降为比模型组低(P<0.05);病理切片观察示干预组两组肾组织硬化程度均比模型组要低(P<0.05)。干预组Western-Blot结果显示干预组Podocin、α-actinin-4蛋白于6周末表达与模型组相较均升高(P<0.05)。 结论:1.苦参碱对阿霉素诱导大鼠肾损害有明显缓解作用;2.苦参碱可能通过影响足细胞蛋白Podocin、α-actinin-4的表达水平从而减轻足细胞的损害,实现对阿霉素所致大鼠肾小球硬化的保护。
Other AbstractObjective:1.To observe the protection of matrine in the adriamycin-induced nephropathy rats. 2.To study the expression of podocin and α-actinin-4 in adriamycin-induced nephropathy rats. Methods:Divide 50 SPF rats randomized in 5 group. Feed rats adaptively for 1 week after removed their left kidney. The rats nephropathy was induced by two injecting adriamycin at 2-week intervals( 1st dose :5mg/kg, 2nd dose: 2.5mg/kg ). Groups: control group(A), sham operation group(B), model group(C), ADR+Matrine 25mg/kg·d group(D), ADR + Matrine 50mg/kg·d group(E). At 2nd,4th,6th week after the establishing of models detect the 24 hours protein of rats urine. Calculate kidney of rats for pathological examination(light microscopic and Electron microscopy),study index of glomeruli sclerosis and detect the expression of podocin and α-actinin-4 at 6th week. Results:1.There was no significant difference between group A and group B in pathological examination and 24 hours protein of rats urine. 2. The results of light microscopic examination shows that glomeruli suffer from wide ranges of glomeruli sclerosis under light microscopic in HE ,PAS, Masson stain in group C. The capillary lumens surround glomeruli expanded, and the fibers proliferated in renal tubulointerstitial. Under observation of electron microscopy we can confirm the fusion of podocyte foot processes and the irregular thickened basal membrane. The epithelial cell of renal tubular lost microvilli, with swelling endothelial cells. The mesangial cells also proliferated, extracellular matrix increased,and there are huge amount proliferation of fibers.Compare control group to model group,the 24 hours protein of rats urine of model group get higher than control group,and continue increased over time. By the observation of pathological biopsy, we found that there are big difference between the index of glomeruli sclerosis in group C and group A(P<0.05).The result of Western-Blot shows the expression of podocin and α-actinin-4 get lower in group C than group A,B(P<0.05).3.After the matrine treatment ,the results of light microscopic examination in HE ,PAS, Masson stain shows less glomeruli sclerosis in group D and E although the thickened basal membrane and proliferation of fibers still exist. The observation of electron microscopy shows lighter fusion of podocyte foot processes, witch slightly injured than group C. At 2th week,the 24 hours protein of rats urine in group D,E get higher than group C(P>...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223145
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
刘亮亮. 苦参碱对阿霉素诱导大鼠肾损害的保护作用及对Podocin、α-actinin-4的影响[D]. 兰州. 兰州大学,2015.
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