父代大鼠长期暴露大气细颗粒物对子代血压及尿钠排泄的影响

Effect of long-term exposure of paternal rats to fine particulate matter on blood pressure and natriuresis in the offsprings

目的 探讨父代大鼠长期暴露大气细颗粒物（fine particulate matter,PM2.5）对其子代血压及尿钠排泄的影响。方法 将20只8~10周龄,体质量180~200 g的雄性SD（Sprague-Dawley）大鼠采用完全随机方法分为暴露组和对照组（n=10）。暴露组经气道滴灌PM2.5混悬液（10 mg/m L,20μL/次,2次/周,共12周）,对照组同法滴灌等量PBS缓冲液。12周后与健康雌性SD大鼠交配分别得到暴露组子代和对照组子代。标准饲料喂养子代大鼠至7~8周龄,体质量180~200 g,用无创鼠尾血压监测仪测定2组子代大鼠血压,代谢笼法收集24 h尿液并测定尿量、尿钠排泄情况,通过肾上腺动脉灌注多巴胺受体激动剂非诺多泮观察肾脏利尿排钠功能,Western blot检测子代大鼠肾脏组织G蛋白偶联受体激酶4（G protein coupled receptor kinase 4,GRK4）、多巴胺Ⅰ类受体（D1DR）蛋白表达情况。结果 与对照组子代相比,暴露组子代血压明显升高[（130.2±2.6）vs（113.0±0.5）,P〈0.05];D1受体介导的利尿排钠功能受损[尿流速：（7.52±1.98）vs（10.71±2.05）,P〈0.05;尿钠排泄率：（522.8±211.1）vs（990.6±231.0）,P〈0.05];子代大鼠肾脏GRK4蛋白水平明显增加[（0.81±0.06）vs（0.67±0.09）,P〈0.05],D1受体蛋白表达降低[（0.53±0.05）vs（0.64±0.04）]。结论 父代大鼠长期暴露PM2.5会引起其子代大鼠成年时期血压升高,可能与PM2.5影响子代肾脏GRK4的表达从而引起D1受体介导的利尿排钠功能障碍相关。

Objective To determine the effect of long-term exposure of paternal rats to fine particulate matter （PM） on blood pressure and natriuresis in the offsprings. Method8 Twenty male Sprague- Dawley （SD） rats （8 weeks old, weighting 180 -200 g） were randomly divided into control group and PM2.5 group （n = 10）. PM2.s suspension was administered by intra-tracheal instillation at a dose of 10 mg/mL, 20 uL once, twice a week for 12 weeks, and the control group was exposed to equal dose of phosphate buffered saline （PBS）. Blood pressure was detected with a noninvasivc tail-cuff method. The offsprings were separately obtained from the 2 groups by mating the male rats with healthy female SD rats, and the blood pressure of the offsprings was measured with the noninvasive tail-cuff method. The natriuresis was detected by metabolic cage. Fenoldopam （D1 receptor agonist） was administrated through suprarenal artery perfusion to determine the function of D1 receptor. Then Western blot assay was performed to assess the protein levels of renal G protein coupledreceptor kinase 4 （GRK4） and D, dopamine receptor （D1DR） in the offsprings. Iqosults Compared with the offsprings from the control group, the offsprings from the PM25 group showed significant increase in blood pressure （ 130.2± 2.6 vs 113.0 ± 0.5, P 〈 0. 05 ） , and significant decrease in urine flow （7.52± 1.98 vs 10.71 ± 2.05, P 〈 0.05 ） and urine sodium excretion （522.8 ± 211.1 vs 990.6± 231.0, P 〈 0. 05 ）. The expression levels of GRK4 （0.81 ± 0.06 vs 0. 67 ±0.09, P 〈 0. 05 ） and D1DR （0. 53±0.05 vs 0. 64± 0.04） were different in the offsprings from the PM25 group. Conclusion Long-term exposure of paternal rats to fine PM significantly increases the blood pressure and decreases natriuresis of the offsprings, which is probably related with renal GRK4 that can regulate the function of D1 DR.