大气细颗粒物对G蛋白偶联受体激酶4的异常调节在尿钠排泄中的作用  

Role of PM_(2. 5) in regulation of G protein-coupled receptor kinase 4 in natriuresis in vitro

作　　者：曾敬[1] 芦茜[1] 陈垦[1] 姚勇刚[1] 张骏[1] 曾春雨[1] 

机构地区：[1]第三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400042

出　　处：《第三军医大学学报》2014年第10期1064-1067,共4页Journal of Third Military Medical University

摘　　要：目的探讨大气细颗粒物(fine particle,fine particulate matter,PM2.5)对G蛋白偶联受体激酶4(G proteincoupled receptor kinase 4,GRK4)的异常调节及其影响尿钠排泄在高血压病发生、发展中的作用。方法以Wistar-Kyoto(WKY)大鼠来源肾脏近曲小管上皮细胞(renal proximal tubule,RPT)株为研究对象,观察在PM2.5刺激对细胞活力、Na+-K+-ATP酶活性以及GRK4、D1R表达的变化;以小干扰RNA(siRNA)技术沉默GRK4,观察PM2.5对Na+-K+-ATP酶活性的影响。结果不同浓度PM2.5(10、50、100μg/mL)处理WKY大鼠RPT细胞株24 h后,细胞活力无明显差异(P>0.05)。PM2.5干预组(100μg/mL)Na+-K+-ATP酶活性明显高于对照组(P<0.05),且对10-6mol/L非诺多泮(fenoldopam)的作用较对照组减低(P<0.05)。不同浓度PM2.5(10、100μg/mL)干预后RPT细胞的GRK4表达明显高于对照组(P<0.05),多巴胺D1受体的蛋白表达明显低于对照组(P<0.05)。以siRNA技术沉默GRK4后,PM2.5对Na+-K+-ATP酶活性的作用较对照组无明显差异(P>0.05)。结论 PM2.5通过调节GRK4表达,进而调控D1受体的表达和Na+-K+-ATP酶活性,参与了对尿钠排泄的调节。Objective G protein-coupled receptor kinase 4 （GRK4） affects renal sodium excretion via impairment of renal dopamine receptor, resulting in sodium retention and an increase in blood pressure. Previous studies pointed out that PM2. s was a risk factor and etiological factor of hypertension. Whether or not PM2.5 is involved in the regulation of GRK4 and renal sodium excretion is investigated in this study. Methods We observed the regulatory effect of PM2.5 on cell viability, Na ＋ -K ＋ -ATPase activity and GRK4 expression in WKY rat renal proximal tubule （RPT） ceils. Moreover, we observed the regulatory effect of PM2.5 on Na＋ -K＋- ATPase activity in WKY rat RPT cells treated by GRK4 siRNA. Results The cell viability showed no difference in WKY rat RFT cells treated by different concentrations of PM2.5 （10, 50, and 100 txg/mL, P 〉0. 05 ）. Compared with controls, Na ＋ -K ＋ -ATPase activity was significantly increased in the cells treated by 100 μg/mL PM2.5 （P 〈 0.05 ）, and decreased by 10-6 mol/L fenoldopam treatment （P 〈 0. 05 ）. PM2.5 leaded to a higher expression of GRK4 and lower expression of dopamine D1 receptor in WKY rat RPT cells （ P 〈 0. 05 ）. Na ＋ - K ＋ -ATPase activity in PM2.5-treated cells showed no difference after blocking GRK4 by siRNA （ P 〉 0. 05 ）. Conclusion PM2.5 increases GRK4 expression, decreases dopamine D1 receptor expression and increases Na ＋ -K ＋ -ATPase activity, showing regulatory effects on renal sodium excretion.

关 键 词：大气细颗粒物 G蛋白偶联受体激酶4 NA+-K+-ATP酶 高血压 

分 类 号：R122.7[医药卫生—环境卫生学] R362[医药卫生—公共卫生与预防医学]