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目的研究大剂量睾酮对小鼠尿路梗阻的影响及其特点。方法 SPF级BLAB/c雄性小鼠45只,体重(20±2)g,完全随机分为A、B和C组,每组15只。B组和C组经皮向腹腔内分别注射丙酸睾酮0.25 mg和1.25 mg,A组以等量生理盐水替代,每天1次,连续20 d。第21 d所有小鼠处死并收集血和尿标本,检测肾功能、性激素、血管内皮生长因子(VEGF)和SELDI-TOF-MS蛋白质谱分析,并解剖观测小鼠双肾、输尿管、膀胱、前列腺及尿道等全尿路情况。结果相比A组,B组为良性前列腺增生(BPH)和单纯下尿路梗阻模型。C组在下尿路梗阻加重基础上出现双输尿管扩张和双肾轻度积水,BUN及Cr(P<0.05)均有升高趋势,但BUN无统计学差异。且蛋白尿阳性,血VEGF升至(9.67±2.67)pg/ml(P<0.01),具有下尿路梗阻继发早期梗阻性肾病特点。此外,C组血清检出11个异常血清蛋白,包括6个蛋白高表达(959.4、5855.1、7519.3、11 840.8、15 074.8、15 880.3 Da),5个蛋白低表达(3496.0、3748.5、4434.0、6057.1、9150.5 Da)。不仅SELDI图形波峰与临床梗阻性肾病相似,且高表达的11 840.8 Da和15 074.8 Da经鉴定分别为可反映肾小球滤过功能受损的β2微球蛋白和血红蛋白家族,而低表达的4434.0 Da和9150.5 Da与急性肾小管坏死的临床患者相符。结论大剂量睾酮可诱导小鼠严重下尿路梗阻,并继发双侧早期梗阻性肾病的方法简易快速有效,且与临床患者在病因机制、血清学和蛋白组学等方面有一些类似特点,具有一定的继续研究和探讨价值。
Objective To study the effects of high-dose testosterone on urinary tract obstruction in mice and its characteristics. Methods 45 SPF male BALB / c mice, weighing 20 ± 2 g, were randomly divided into A, B and C groups, 15 in each. Group B and group C were percutaneously injected intraperitoneally with testosterone propionate 0.25 mg and 1.25 mg, respectively, and group A with normal saline instead of normal saline for 20 days. The mice were sacrificed on the 21st day and blood and urine samples were collected for detection of renal function, sex hormones, vascular endothelial growth factor (VEGF) and SELDI-TOF-MS protein profiles and anatomical observations of the kidneys, ureter, bladder and prostate in mice And urinary tract and other urinary tract conditions. Results Compared with group A, group B was a model of benign prostatic hyperplasia (BPH) and simple lower urinary tract obstruction. In group C, bilateral ureteral dilatation and mild hydronephrosis occurred on the basis of the increase of lower urinary tract obstruction. The BUN and Cr (all P <0.05) showed an increasing tendency, but there was no statistical difference between the two groups. The proteinuria was positive and the serum VEGF increased to (9.67 ± 2.67) pg / ml (P <0.01). It had the characteristics of early obstructive nephropathy secondary to lower urinary tract obstruction. In addition, 11 abnormal serum proteins were detected in serum of group C, including 6 proteins highly expressed (959.4, 5855.1, 7519.3, 11404, 15 074.8, 15 880.3 Da), 5 proteins low expressed (3496.0, 3748.5, 4434.0, 6057.1 , 9150.5 Da). Not only was the SELDI pattern peak similar to clinical obstructive nephropathy, but the high expression of 11 840.8 Da and 15 074.8 Da were identified as β2 microglobulin and hemoglobin families, respectively, that could reflect impaired glomerular filtration, whereas the low expression of 4434.0 Da and 9150.5 Da are consistent with clinical patients with acute tubular necrosis. Conclusion High-dose testosterone can induce severe lower urinary tract obstruction in mice and secondary to early bilateral obstructive nephropathy, the method is simple, quick and effective, and has some similarities with clinical patients in etiology and pathogenesis, serology and proteomics, Have some continued research and explore the value.