氯沙坦钾对慢性心力衰竭小鼠肾脏水通道蛋白2表达的影响

Expression and Significance of Aquaporin-2 in kidney in Mice with Chronic Heart Failure

目的探讨慢性心力衰竭小鼠肾脏水通道蛋白2(AQP-2)的表达。了解氯沙坦钾对慢性心衰小鼠肾脏 AQP-2表达的影响。方法昆明小鼠33只随机分为3组:假手术组(n=10);慢性心力衰竭组(CHF 组,n=13);氯沙坦钾组(n=10)。以左冠状动脉结扎建立小鼠 CHF 模型,其中氯沙坦钾组在结扎术后2周给予氯沙坦钾(10 mg/kg·d)灌胃8周。观察各组小鼠一般情况、心率、血压、肾/体质量及死亡率。光镜下观察 HE 染色后小鼠肾组织的病理改变;用逆转录聚合酶链反应(RT-PCR)法检测小鼠肾脏组织 AQP-2 mRNA 的表达;用免疫组织化学和 Western blot 分析法检测肾组织 AQP-2蛋白的表达。结果假手术组小鼠术后8周均存活,且一般情况佳;CHF 组死亡3只(23%);氯沙坦钾组小鼠术后8周均存活。与假手术组比较,CHF 组小鼠心率、收缩压(SBP)、舒张压(DBP)、肾/体质量均显著增高(P<0.05);氯沙坦钾组以上各项指标较 CHF 组显著下降(P<0.01),但仍高于假手术组。CHF 小鼠肾小管上皮细胞有明显空泡形成,经氯沙坦钾治疗后病理改变有所减轻。CHF 小鼠肾组织AQP-2基因和蛋白表达均显著高于假手术组,经氯沙坦钾治疗后表达有所下调,但仍高于假手术组。结论 CHF小鼠肾组织存在 AQP-2基因和蛋白表达增加,氯沙坦钾在保护肾脏的同时下调肾组织 AQP-2基因及蛋白的表达。

Objective To determine the expression of renal aquaporin-2（AQP-2） of mouse with chronic heart failure（CHF） and the effect of losartan on the expression of renal AQP-2 of mouse with CHF. Methods Experimental CHF models were established by coronary artery ligation. Thirty three Kunming mouse were grouped as follows： sham operated group（n=10）, CHF group（n=13） , losartan potassium treatment group [10 mg/（kg · d） by garage, n=10] for 8 weeks. Heart rate, blood pressure, renal/body mass rate and mortality of all mouse were determined. The expression of mouse renal AQP-2 mRNA was analysed with RT-PCR. Immunohistochemical and Western blot methods were used to determine the expression of renal AQP-2 protein. Results After 8 weeks of operation, all mouse in sham operated group survived, 3 mouse in CHF group died（3/13） and all mouse in losar- tan potassium group survived. Compared with sham operated group, heart rate, systolic blood pressure （SBP）, di- astolic blood pressure（DBP）, renal/body mass rate of mouse in CHF group were significantly increased （P〈0. 05 ）, losartan decreased these indices significantly（P〈0. 01 ）, but remained higher than in sham operated group. Losartan significantly decreases the vacuole and renal AQP-2 gene and protein expression in renal tubule in CHF mice. Condmion The losartan potassium downregulated the increased renal AQP-2 gene and protein expression in CHF mice.