高盐饮食对自发性高血压大鼠肾髓质环氧化酶2表达的影响  

Regulation of cyclooxygenase 2 expression in renal medulla of spontaneous hypertensive rats by dietary salt intake

作　　者：王少清[1] 陈靖[1] 尤莉[1] 张力胤[1] 陶琳[1] 张敏敏[1] 周江华[1] 郝传明[1] 顾勇[1] 

机构地区：[1]复旦大学附属华山医院肾病科,上海200040

出　　处：《中华肾脏病杂志》2007年第11期716-721,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金（30400211）;教育部“211工程”二期重点建设学科基金

摘　　要：目的观察自发性高血压大鼠（SHR）肾髓质环氧化酶2（COX2）的表达以及不同盐负荷状态下COX2的变化。方法6周龄SHR大鼠及其对照Wistar-Kyoto（WKY）大鼠各12只，随机分为低盐组和高盐组（WKY-LS组，WKY-HS组，SHR-LS组，SHR-HS组），分别给予高盐（含8％NaCl）或低盐（含O．04％NaCl）饮食3d。观察基础状态及不同盐负荷前后大鼠尾动脉血压、24h尿量（UV）、尿钠（UNa）以及COX2代谢物6k．PGFlα排泄情况。应用免疫组化和Western印迹的方法检测肾髓质COX2蛋白表达。结果给予不同盐负荷3d后，SHR-Hs组血压显著升高[（12．59±5．13）比（11．94±3．76）mmHg，P〈0．05]。基础状态及不同盐负荷状态下，SHR大鼠24hUV、UNa排泄与WKY大鼠相比均显著下降（P均〈O．05）。与各自基础状态相比，低盐饮食后两种大鼠的UV和UNa排泄显著降低；高盐饮食后则显著增加（P均〈O．05）。SHR和WKY大鼠尿COX2代谢物6k-PGFlα的排泄对盐负荷的反应也类似，高盐组均较低盐组显著增加（P〈0．05），但同样盐负荷状态下两组之间差异无统计学意义。基础状态下及低盐饮食SHR与WKY大鼠肾髓质COX2表达差异无统计学意义；给予高盐饮食后WKY大鼠肾髓质COX2表达增加2．06倍，SHR大鼠增加1．87倍，但两种大鼠之间差异无统计学意义。结论SHR大鼠肾脏水盐排泄功能受损，高盐饮食后血压进一步升高，水钠潴留，同时伴有肾髓质COX2表达升高，但不同盐负荷对SHR大鼠肾髓质COX2表达的影响与WKY大鼠相同。提示肾髓质COX2参与了水盐代谢的调节，且在SHR大鼠中表达正常，但并非该动物模型高血压形成及水钠潴留的关键因素。Objective To investigate the effects of dietary salt intake on the expression of cyclooxygenase 2 （COX2） in renal medulla of spontaneously hypertensive rats （SHR） and normahensive Wistar-Kyoto rats （WKY）. Methods Rats at age of 6 weeks were randomly assigned to the following groups （n=6）： WKY rats were fed with low salt diet containing 0.04% NaC1 （WKY-LS）, WKY with high salt diet containing 8% NaC1 （WKY-HS）, and SHR with low salt diet （SHR-LS）, SHR with high salt diet （SHR-HS）. The blood pressure （BP） was determined by automatic sphygmomanometer at the tail artery. The urine volume （UV） and urinary sodium excretion （UNa） were also measured. Urinary level of 6-keto prostaglandin Flα （6k-PGFIα） was detected by radioimmunity. Protein expressive level of COX2 in the renal medulla was assessed by immunohistochemistry and Western blot. Results The average baseline BP of SHR groups, measured 1 day before the start of the salt diet, was significantly higher than that of WKY groups （P〈O.05）. After 3 days of different salt diet, BP of WKY-LS, WKY-HS and SHR-LS did not change obviously （P〉O.05）, while BP of SHR-HS group was significantly enhanced compared to basal level （P〈O.05）. Both UV and UNa of SHR groups were significantly lower compared with those of WKY groups regardless of normal, low or high salt diet provided（P〈O.05）. Levels of UV and UNa significantly increased in all the groups treated with high salt diet and decreased in those allotted low salt food, compared to baseline levels（P〈O.05）. Urinary levels of COX2 metabolite 6k- PGFlα in both SHR and WKY groups responded similarly to dietary salt intake. Groups of high salt diet exerting an obvious increase and groups of low salt diet exhibiting a drop （P〈O.05） with no variance were found between SHR and WKY having the same salt-loading （P〉O.05）. Renal COX2 staining was mainly localized in medullary interstitial cells by immunohistochemistry. High salt diet for 1 week incr

关 键 词：高血压 大鼠 近交SHR 氯化钠 环氧化酶2 肾脏髓质 水 钠潴留 

分 类 号：R686[医药卫生—骨科学]