CAJ | 학술논문

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、11840.8、15074.8、15880.3 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11840.8 Da和15074.8 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。
목적연구대제량고동대소서뇨로경조적영향급기특점。방법 SPF급BLAB/c웅성소서45지，체중（20±2） g，완전수궤분위A、B화C조，매조15지。 B조화C조경피향복강내분별주사병산고동0.25 mg화1.25 mg，A조이등량생리염수체대，매천1차，련속20 d。제21 d소유소서처사병수집혈화뇨표본，검측신공능、성격소、혈관내피생장인자（ VEGF）화SELDI-TOF-MS단백질보분석，병해부관측소서쌍신、수뇨관、방광、전렬선급뇨도등전뇨로정황。결과상비A조，B조위량성전렬선증생（ BPH）화단순하뇨로경조모형。 C조재하뇨로경조가중기출상출현쌍수뇨관확장화쌍신경도적수，BUN급Cr（P＜0.05）균유승고추세，단BUN무통계학차이。차단백뇨양성，혈VEGF승지（9.67±2.67）pg/ml（P＜0.01），구유하뇨로경조계발조기경조성신병특점。차외，C조혈청검출11개이상혈청단백，포괄6개단백고표체（959.4、5855.1、7519.3、11840.8、15074.8、15880.3 Da），5개단백저표체（3496.0、3748.5、4434.0、6057.1、9150.5 Da）。불부SELDI도형파봉여림상경조성신병상사，차고표체적11840.8 Da화15074.8 Da경감정분별위가반영신소구려과공능수손적β2미구단백화혈홍단백가족，이저표체적4434.0 Da화9150.5 Da여급성신소관배사적림상환자상부。결론대제량고동가유도소서엄중하뇨로경조，병계발쌍측조기경조성신병적방법간역쾌속유효，차여림상환자재병인궤제、혈청학화단백조학등방면유일사유사특점，구유일정적계속연구화탐토개치。
Objective To study the effects and characteristics of whole urinary obstruction of mice induced by high-dose testosterone .Methods Forty five BLAB/c male mice, weight ( 20 ±2 ) g, were completely randomly divided into 3 groups as A,B and C.Each mouse in group B and group C was injected with testosterone propionate 0.25 mg and 1.25 mg into abdominal cavity respectively ,whereas the other mice in group A were only injected with saline solutions instead .All mice were daily injected for continuous 20 d.Till the end of 21 d,all mice were sacrificed and their sera and urine specimens were collected for renal function , sexual hormones , vascular endothelial growth factor(VEGF)and SELDI-TOF-MS protein spectrum analyses.On the other hand,some anatomical studies on mice urinary tracts were also carried out .Results Compared to group A , group B contributed us benign prostatic hyperplasia ( BPH ) and lower urinary tract obstruction model .As to group C, however, mild expansion and hydronephrosis in bilateral upper urinary tract had happened resulted from severe lower urinary tract obstruction .In group C,moreover,serum BUN(P>0.05),Cr(P<0.05)were both increased accompanied with mild proteinuria, and serum VEGF was also increased to (9.67 ±2.67)pg/ml(P <0.01).What′s more,the group C had been discovered 11 anomalous proteins , including 6 proteins in high-expression ( 959.4 , 5855.1 , 7519.3 , 11 840.8 , 15 074.8,15 880.3 Da)and 5 in low-expression(3496.0,3748.5,4434.0,6057.1,9150.5 Da).The SELDI graphic peaks were very similar to clinical patients of obstructive nephropathy .Not only high-expression proteins of 11 840.8 Da and 15 074.8 Da were speculated as β2-microglobulin and hemoglobin family series that could probably reflect the glomerular filtration function , but also low-expression proteins of 4434.0 Da and 9150.5 Da were very close to clinical patients of acute tubular necrosis .Conclusion The lower urinary tract obstruction and early bilateral obstructive nephropathy induced by high-dose testosterone in mice is not only easy and effective ,but also has many similar characteristics with clinical patients in etiology ,serology and proteomics ,which probably deserved us to further study in future .