中文摘要：

目的探讨孕期糖尿病大鼠子代肾脏血管紧张素Ⅱ1型受体（angiotensinⅡtype 1receptor,AT1R）在子代高血压发生中的作用及其机制。方法将20周龄SD雌性大鼠20只（体质量250-280 g）分别与20只SD雄性大鼠（体质量250-280 g）进行交配。将次日见阴栓的雌鼠视为孕鼠（阴栓为白色结晶状颗粒）,得到12只孕鼠,分为糖尿病组孕鼠和对照组孕鼠,每组6只。糖尿病组孕鼠在孕期第0天单次腹腔注射链菌霉素（STZ）35 mg/kg,对照组孕鼠注射等体积生理盐水。采用鼠尾无创血压测量法持续监测子代大鼠血压;分别从糖尿病组孕鼠和对照组孕鼠的子代大鼠中各随机选取6只20周龄雄性大鼠（体质量250-280 g）用于实验。代谢笼测定24 h尿量,肾上腺动脉灌注AT1R阻断剂（坎地沙坦）测定尿钠排泄;qRT-PCR检测大鼠肾脏AT1R的mRNA表达;免疫印迹检测大鼠肾脏AT1R的蛋白表达。结果 12、16、20、24周龄时,糖尿病组子代大鼠血压均高于同龄期对照组子代大鼠[分别为（118±4）vs（105±3）,（124±2）vs（114±2）,（135±3）vs（118±2）,（140±4）vs（120±3）mm Hg,P〈0.05]。24 h尿液分析结果显示,STZ组子代大鼠的基础尿量及尿钠排泄率明显低于对照组子代大鼠[（558.8±40.5）vs（764.3±87.6）μmol/（kg·d）,P〈0.05]。肾上腺动脉灌注AT1受体阻断剂后,糖尿病组子代大鼠的排钠利尿作用明显高于对照组[（1 560±87）vs（760±60）μL/min,P〈0.05],其肾脏AT1R的蛋白表达及mRNA均显著高于对照组[（1.27±0.08）vs（0.57±0.05）,（1.2±0.1）vs（0.5±0.2）,P〈0.05]。结论孕期糖尿病导致大鼠子代血压升高,其可能机制是子代大鼠肾脏AT1R的蛋白表达增高,体内存在水钠潴留所致。

英文摘要：

Objective To explore the role of renal angiotensin II type-1 receptor（ AT1R） in hypertensive offsprings of rats with maternal diabetes and related mechanism. Methods Twenty SD female rats（ 20 week-old） with body weight of 250- 280 g were mated with 20 SD male rats with body weight of250- 280 g,and the female rats with vaginal plug of white crystalline particles were determined as pregnant rats. Twelve pregnant rats were divided into diabetic group（ n = 6） and control group（ n = 6）. On day 0 of gestation,the diabetic group was treated by single intraperitoneal injection of streptozotocin（ 35 mg / kg）,while the control group was injected with normal saline. Systolic blood pressure（ SBP） of the offsprings was monitored by tail-cuff non-invasive continuous blood pressure system. Six 20-week-old offsprings with body weight of 250- 280 g were randomly selected from the diabetes group and the control group respectively to detect 24-hour urine flow using stainless steel metabolic cages and urinary sodium excretion with suprarenal artery administration of AT1 R antagonist candesartan. The renal AT1 R mRNA levels were measured by qRTPCR,while the AT1 R protein levels were detected by Western blotting. Results The SBP of the postnatal offsprings from the diabetes group was higher than that from the control group in the 12 nd,16th,20 th and24th weeks（ 118 ± 4 vs 105 ± 3,124 ± 2 vs 114 ± 2,135 ± 3 vs 118 ± 2,and 140 ± 4 vs 120 ± 3 mm Hg,respectively,all P〈0. 05）. The 24-hour urine analysis showed that the basic urine flow and urinary sodium excretion rate of the offsprings from the diabetes group were significantly lower than those from the control group [558. 8 ± 40. 5 vs 764. 3 ± 87. 6 μmol /（ kg·d）,P〈0. 05]. The candesartan-induced natriuretic and diuretic effect in the offsprings from the diabetes group was stronger than that in the offsprings from the control group（ 1 560 ± 87 vs 760 ± 60 μL / min,P〈0. 05）. Moreover,the renal AT1 R at mRNA and protein levels in the