妊娠期糖尿病对子代大鼠肾脏多巴胺D1受体介导的尿钠排泄功能的影响  

Effects of gestational diabetes on the urinary sodium excretion mediated by the renal dopamine D_1 receptor in rat offspring

作　　者：罗浩[1] 陈彩宇[1] 罗晓丽[1] 王红勇[1] 曾春雨[1] LUO Hao;CHEN Cai-yu;LUO Xiao-li;WNAG Hong-yong;ZENG Chun-yu(Department of Cardiology,Chongqing Institute of Cardiology,Chongqing Key Laboratory for Hypertension Chongqing Cardiovascular Clinical Research Center,Daping Hospital（Field Surgery Research Institute）,Third Military Medical University,Chongqing 400042,China)

机构地区：[1]陆军军医大学大坪医院(野战外科研究所)心血管内科,重庆市心血管病研究所,重庆市高血压研究重点实验室,重庆市心血管病临床医学研究中心,重庆400042

出　　处：《中华高血压杂志》2018年第10期934-940,共7页Chinese Journal of Hypertension

基　　金：国家自然科学基金项目(31500931);重庆市基础科学与前沿技术研究专项(cstc2016jcyjA0057,cstc2017jcyjAX0153)

摘　　要：目的探讨妊娠期糖尿病对子代大鼠肾脏多巴胺D1受体介导的尿钠排泄功能的影响。方法将SpragueDawley(SD)孕鼠随机分为妊娠期对照组(10只)和妊娠期糖尿病组(10只),妊娠期糖尿病组大鼠在孕期第0天腹腔注射链脲佐菌素(STZ,35mg/kg),而妊娠期对照组大鼠给予注射等体积的0.9%生理盐水。子代大鼠出生后,分别从2组中按随机数字表法选取20只雄性大鼠进行实验。采用无创鼠尾测压仪从4周龄连续检测子代大鼠血压至16周;代谢笼收集16周龄子代大鼠24h尿液;酶联免疫吸附试验(ELISA)法检测16周龄子代大鼠肾脏丙二醛和超氧化物歧化酶(SOD)活性;肾上腺动脉灌注多巴胺D1受体激动剂(Fenoldopam)测定其介导的尿钠排泄功能;进一步检测肾脏G蛋白耦联受体激酶4(GRK4)、多巴胺D1受体的表达及磷酸化水平。结果 12、14、16周龄妊娠期糖尿病子代大鼠血压明显高于妊娠期对照组子代大鼠[(134±4)比(123±4),(138±6)比(126±3),(141±5)比(124±5)mm Hg,均P<0.05];糖尿病母鼠的子代24h尿量及尿钠排泄率明显低于妊娠期对照组子代大鼠(P<0.05);通过肾上腺动脉灌注Fenoldopam,其介导的排钠利尿作用(尿流速和尿钠排泄率)明显低于妊娠期对照组子代大鼠(P<0.05)。与妊娠期对照组子代大鼠比较,糖尿病母鼠的子代丙二醛水平明显升高,而SOD活性明显降低(P<0.05)。糖尿病母鼠的子代肾脏GRK4表达及多巴胺D1受体磷酸化水平显著高于妊娠期对照组子代大鼠(P<0.05)。结论妊娠期糖尿病引起子代大鼠肾脏多巴胺D1受体功能受损,其机制可能与氧化应激水平升高,引起肾脏GRK4表达增加,导致肾脏多巴胺D1受体过度磷酸化有关,其可能是引起子代大鼠高血压发生的重要机制之一。Objective To investigate the effects of maternal gestational diabetes （MGD） on the urinary sodium excretion mediated by the renal dopamine D1 receptor in rat offspring. Methods The pregnant Sprague Dawley （SD） rats were randomly divided into gestational control group （ n = 10 ） and gestational diabetes group （ n = 10 ）. The rats in gestational diabetes group were intraperitoneally injected gestation, in each group measured by d the gestational were randomly non-invasive tail selected after ere given an equal v birth. The blood with streptozotocin （STZ, 35 mg/kg） on day 0 of olume of 0.9 % saline. Twenty male offspring rats pressure of the offspring aged 4 to 16 weeks were cuff method. And the 24-hour urine volume and sodium excretion of the offspring at the age of 16 weeks were collected by metabolic cages. The activity of malondialdehyde （MDA） and superoxide dis mutase （SOD） in kidneys of the offspring at the age of 16 weeks were measured by enzyme-linked immunosorbent as say （ELISA）. The D1 receptor-mediated urinary sodium excretion was detected by the stimulation of renal Dl-like re ceptor wl coupled r th fenoldopam through suprarenal artery infusion. Furthermore, the protein expression of renal G protein eceptor kinase 4 （ GRK4 ）, dopamine D1 receptor and the phosphorylation level of D1 receptor were analyzed.Results The blood pressure in the MGD offspring at the age of 12, 14, 16 weeks was significantly higher than that in control offspring [（134±4） vs （123±4）, （138±6） vs （126±3）, （141±5） vs （124±5） mm Hg,allP〈0.05]. The 24-hour urine volume and sodium excretion rate in MGD offspring were significantly lower than those in the control offspring （P〈0.05）. The urinary flow rate and sodium excretion mediated by perfusing fenoldopam through suprarenal artery were significantly lower in the MGD offspring than those in the control offspring （P〈0.05）. Compared with the control offspring, the level of MDA in the MGD offspring was signif

关 键 词：妊娠期糖尿病 子代 高血压 肾脏 多巴胺 

分 类 号：R714.256[医药卫生—妇产科学]