兰州大学机构库 >学院待认领
苦参碱对肾小球硬化大鼠MMP-1、TIMP-1表达的影响
Alternative TitleThe effect of matrine on MMP-1、TIMP-1 in Adriamycin-induced glomerular sclerosis rat
曹彦星
Thesis Advisor金玉
2009-05-17
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
Keyword苦参碱 肾小球硬化 阿霉素 基质金属蛋白酶-1 基质金属蛋白酶组织抑制剂-1 大鼠
Abstract目的: 观察苦参碱对阿霉素肾小球硬化大鼠慢性肾脏损害的保护作用及其对基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶组织抑制因子-1(TIMP-1)、a-平滑肌肌动蛋白(a-SMA)及Ⅳ型胶原蛋白(Col-Ⅳ)在肾小球硬化过程中表达的影响,探讨苦参碱对肾小球硬化的治疗作用及其机制,为氧化苦参碱在临床抗肾小球硬化中的应用提供理论依据。 方法: 96只健康雄性Wistar大鼠随机分为4组:正常对照组(A组)、模型组(B组)、苦参碱大剂量(75mg.kg-1.d-1)治疗组(C组)、苦参碱小剂量(25mg.kg-1.d-1)治疗组(D组)各24只。用单侧肾切除一周后尾静脉注射阿霉素(5mg/kg)的方法建立肾小球硬化大鼠模型,设假手术组为正常对照组。注射阿霉素后各治疗组予以相应剂量的苦参碱肌肉注射(1次/日)。2、4、6周分批处死每组各8只大鼠,观察尿蛋白、血清尿素氮、肌酐、白蛋白,HE染色观察肾脏病理指标的改变,并用免疫组化法检测肾组织基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶组织抑制因子-1(TIMP-1)、a-平滑肌肌动蛋白(a-SMA)及Ⅳ型胶原蛋白(Col-Ⅳ)表达,采用实时荧光定量PCR(RT-PCR)技术观察大鼠肾组织MMP-1、TIMP-1 mRNA的表达。动物实验时间8周。 结果: 1.与正常对照组相比,模型组不同时间尿蛋白水平明显升高,血清肌酐和尿素氮水平升高,血清白蛋白降低,肾小球硬化指数升高(P<0.01)。D组比较模型组尿蛋白排泄量明显减少,血清肌酐和尿素氮水平下降,肾小球系膜增生、硬化程度明显减轻(P<0.05或P<0.01); 2. 免疫组化显示:a-SMA、Col-Ⅳ表达随肾小球硬化程度而升高,以模型组为著,苦参碱小剂量组(D组)较低,两者间差异有统计学意义(P<0.05) ;MMP-1、TIMP-1表达趋势与实时荧光定量PCR (RT-PCR)结果一致,随着肾小球硬化严重程度而降低,苦参碱小剂量组(D组)最低,同各组差异有统计学意义 (P<0.05)。 结论:苦参碱对阿霉素肾小球硬化大鼠的慢性肾脏损害有一定的保护作用,其机制可能与影响MMP-I及TIMP-1的表达,从而减少ECM在肾脏的沉积进而延缓肾脏纤维化进程有关。
Other AbstractObjective: To observe the effect of matrine on MMP1and TIMP1 in adriamycin-induced glomerulosclerosis in rats and explore its protective mechanisms. Methods: 96 male Wistar rats were performed in experiments. The rats were randomly divided into 4 groups: normal control group (A group), model control group (B group), matrine 75mg.kg-1.d-1 treated group (C group), matrine25mg.kg-1.d-1 treated group (D group). Adriamycin nephropathy was induced by a single tail intravenous injection of adriamycin(5mg/kg)after the left kideny was cut off one week .Matrine was used for injection from the first day after the injection of adriamycin until the end of the study. Eight rats were sacrificed every 2 weeks in each group for blood biochemical analyses and histological study. Urinary protein (mg/24h), the concentration of serum creatinine (Cr), blood urea nitrogen (BUN), serum albumin (Alb) were measured at 2 ,4 and 6 weeks, and a semiquantitative score was used to evaluate the degree of glomerular lesions. immunohistochemistry was to examine the expression of MMP1、TIMP1. Finally,the expressions of MMP1 and TIMP1 mRNA were measured by real-time RT-PCR. Results: Matrine not only reduced urinary protein, Cr, BUN in blood, but also significantly ameliorated glomerular sclerosis (P<0.05 or P<0.01). Meanwhile immunohistoche- mistry staining indicated that a-SMA、Col-Ⅳ MMP-1 expression increased and TIMP-1 expression decreased in B group (model control group) compared with the 2 treated groups and A group (P<0.05 or P<0.01). D group (Oxymatrine 75 mg.kg-1.d-1 treated group) had advantages over C group (oxymatrine 25 mg.kg-1.d-1 treated group) and B group (model control group)(P<0.05), but inadvantages over A group(normol group). (P<0.05) Conclusion: Matrine has depressive role on the developing of glomerular sclerosis in Adriamycin-induced nephropathy rats .Its mechanism is considered to be relevant to intervention of MMP1/TIMP1. [Keywords] matrine , glomerular sclerosis , MMP-1 ,TIMP-1 ,a-SMA,Col-Ⅳ,rat , Adriamycin
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223139
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
曹彦星. 苦参碱对肾小球硬化大鼠MMP-1、TIMP-1表达的影响[D]. 兰州. 兰州大学,2009.
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