机构地区:[1]郑州大学第一附属医院病理科,450052 [2]郑州大学第一附属医院泌尿外科尿动力学中心,450052 [3]郑州大学第一附属医院急诊科,450052 [4]郑州大学第一附属医院泌尿外科尿动力学中心河南省高等学校临床医学重点学科开放实验室,450052
出 处:《中华实验外科杂志》2013年第6期1126-1128,共3页Chinese Journal of Experimental Surgery
摘 要:目的观察替米沙坦对双侧输尿管梗阻(BUO)大鼠水电解质紊乱和肾脏水通道蛋白2(AQP2)表达的影响。方法慕尼黑大鼠36只,随机分为BUO组、替米沙坦组(TEL组)和对照组(Sham组),每组12只。BUO组和TEL组均行双侧输尿管结扎术,Sham组仅游离输尿管但不结扎。TEL组每天TEL液灌胃[5mg/(kg·d)],BUO组和Sham组同体积生理盐水灌胃。双侧输尿管梗阻24h后解除梗阻,第4天收集血液和肾脏标本,采用免疫组织化学和Westernblot技术检测肾脏AQP2表达。结果BUO组与Sham组比较,尿量显著增高[(93±6)μL/(min·kg)比(26±4)μL/(min·kg)],尿比重和尿钠显著降低[1.007±0.007比1.024±0.017;(43.25±6.99)mmol/L比(182.37±17.91)mmol/L],血肌酐和血清钾显著增高[(66.22±6.03)μmol/L比(33.89±2.97)μmol/L;(5.57±0.37)mmol/L比(4.29±0.09)mmol/L]。TEL组与BUO组比较,尿量硅著降低(54±6)μL/(min·kg)比(93±6)μL(min·kg),尿比重和尿钠湿著升高[1.017±0.009比1.007±0.007;(82.23±12.98)mmol/L比(43.25±6.99)mmol/L],血肌酐和血清钾显著降低[(42.83±1.51)μmol/L比(66.22±6.03)μmol/L;(4.69±0.21)mmol/L比(5.57±0.37)mmoL/L]。AQP2表达BUO组显著低于Sham组,TEL组显著高于BUO组,各组比较差异有统计学意义(P〈0.05)。结论替米沙坦可抑制AQP2蛋白表达下调,减轻BUO解除后肾脏低渗性尿,保护肾脏功能。Objective To explore the molecular mechanism of renal function defects after bilateral ureteral obstruction (BUO) and investigate the effect of telmisartan (TEL) on the expression of renal aqua- porin 2 following BUO in rats. Methods Thirty-six Munich-Wistar rats were randomly divided into three groups (BUO,n = 12; TEL, n = 12; Sham, n = 12). The BUO model was built in BUO and TEL groups by bilateral ureteral ligation. Age- and time-matched sham-operated controls were prepared. The rats in TEL group were fed on TEL [5 mg/(kg.d) ] every day. BUO was released 24 h after BUO, and at the 4th day the blood samples were collected and kidneys were harvested to examine the effects of TEL on the dysregula- tion of AQP2 by using semi quantitative immunoblottling and immunohistochemistry. Results BUO resulted in a marked polyuria [BUO vs. sham: (93 ±6) ixL/(min·kg) vs. (26 ±4) μL/(min·kg) ,n= 12;P〈 0. 05] and a reduced urine specific gravity [BUO vs. sham: 1. 007 ±0. 007 vs. 1. 024 ±0. 017,n = 12;P 〈 0.05] and urine Na [(43.25 ±6.99) mmol/L vs. (182.37 ±17.91) mmol/L,n=12;P〈0.05], an increased Scr [ (66. 22 ± 6. 03) μmol/L vs. (33.89 ±2. 97 )μmol/L, n = 12 ;P 〈 0. 05 ] and serum potassium [ (5.57±0. 37) mmoL/L vs. (4. 29 ±0. 09) mmol/L,n = 12;P 〈0. 05). Administration of TEL partly pre-vented this increase in postobstructive urine production [ ( 54 ± 6) vs. ( 93 ± 6 ) μL ( min. kg), n=12 ; P 〈 0. 05 ], and decrease in urine specific gravity ( 1. 017 ± 0. 009 vs. 1. 007 ± 0. 007, n = 12 ; P 〈 0. 05 ). The Scr and serum potassium levels were lower significantly in TEL group than in BUO group [ (42. 83 ± 1.51 ) μmol/L vs. (66. 22 ± 6. 03 )μmoL/L ; ( 4. 69 ± 0. 21 ) mmol/L vs. ( 5. 57 ± 0. 37 ) retool/L, n = 12 ; P 〈 0.05 ]. BUO resulted in a significantly decreased expression of AQP2 as compared with controls, and TEE prevented the reduction of AQP2 ( P 〈 0. 05 ). Conclusion TEL prevents
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