论文部分内容阅读
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 investigate the effects of long-term exposure to PM2.5 on the offspring blood pressure and urinary sodium excretion in the offspring rats. Methods Twenty male Sprague-Dawley rats (8-10 weeks old and 180-200 g body weight) were randomly divided into exposed group and control group (n = 10). In the exposed group, PM2.5 suspension (10 mg / m L, 20 μL / time, 2 times / week for 12 weeks) was dripped by airway. In the control group, the same volume of PBS was dripped. Twelve weeks later, healthy female SD rats were mated to progeny and control progeny of the exposed group. The standard diet was fed to the offspring of rats to 7-8 weeks of age and the body weight was 180-200 g. The blood pressure of the offspring of two groups was measured by noninvasive mouse tail blood pressure monitor, the urine of 24 h was collected by metabolic cage method, Urinary sodium excretion was measured by adrenal artery perfusion dopamine agonist fenoldopan renal diuretic sodium function, Western blot detection of offspring rat kidney G protein-coupled receptor kinase 4 (G protein coupled receptor kinase 4, GRK4), dopamine class I receptor (D1DR) protein expression. Results Compared with the progeny of the control group, the blood pressure in the progeny of the exposed group was significantly higher than that of the control group [(130.2 ± 2.6) vs (113.0 ± 0.5), P <0.05]. The D1 receptor- : (7.52 ± 1.98) vs (10.71 ± 2.05), P <0.05; urinary sodium excretion rate was (522.8 ± 211.1) vs (990.6 ± 231.0), P <0.05] (0.81 ± 0.06) vs (0.67 ± 0.09), P <0.05], and decreased the expression of D1 receptor protein [(0.53 ± 0.05) vs (0.64 ± 0.04)]. Conclusion Long-term exposure of PM2.5 to the adult male rats results in an increase of blood pressure in the offspring of adult offspring rats. It may be related to the effect of PM2.5 on the expression of GRK4 in the kidney and the D1 receptor-mediated dysfunction of natriuresis.