摘要
目的 观察人近端肾小管上皮细胞能否合成组织醛固酮(ALDO),以及内皮素-1 (ET-1)对该作用的影响。方法 利用体外培养的人近端肾小管上皮细胞系(HKC)进行试验,采用放射免疫方法对醛固酮进行检测。(1)刺激试验:观察HKC细胞受不同浓度和不同作用时间的ET 1刺激后,醛固酮及血管紧张素Ⅱ(AngⅡ)生成量的变化。(2)抑制试验:固定ET -1刺激条件,观察不同浓度和不同作用时间的血管紧张素转换酶抑制剂(ACEI)对HKC细胞生成血管紧张素Ⅱ及醛固酮的影响。结果 (1)未加任何刺激的HKC细胞能产生基础量醛固酮及血管紧张素Ⅱ。ET- 1刺激后醛固酮及血管紧张素Ⅱ的生成量均呈剂量依赖及时间依赖性增加, 10-9及10-7 mol/LET-1刺激48h后醛固酮及血管紧张素Ⅱ的生成量显著高于0mol/LET -1组(P<0 .05或0. 01); 10-7 mol/L的ET -1刺激12h、24h及48h后醛固酮及血管紧张素Ⅱ的生成量也显著高于0h组(P<0.05或0. 01)。(2)用10-7 mol/LET 1与不同浓度的ACEI共同孵育HKC细胞48h,结果10-9、10-7及10-5 mol/L的ACEI能使血管紧张素Ⅱ及醛固酮生成量显著减少(与0mol/LACEI组比较P<0. 01 ),但是,此浓度的ACEI虽能完全阻断血管紧张素Ⅱ生成,却未能完全阻断醛固酮生成;用10-7 mol/LET 1与10-5 mol/LACEI共同孵育HKC细胞,并在不同时间段进行?
Objective To observe whether local aldosterone (ALDO) may be synthesized by hum an renal proximal tubular cell lines (HKC) and investigate whether endothelin-1 (ET-1) has effects on the production of local ALDO.Methods The following tests were performed: (1) stimulative tests: after the HKC cells were incubated with ET-1 in different concentration (0, 10 -11, 10 -9, 10 -7 mol/L) or for different time (0, 6, 12, 24, 48 h), the le vels of ALDO and angiotensinⅡ (AngⅡ) in the media were measured by radioimmun oassay. (2) inhibitive test: after the HKC cells were incubated with different concentration of angiotensin converting enzyme inhibitor (ACEI) (0, 10 -11, 10 -9, 10 -7, 10 -5 mol/L) and ET-1 (10 -7 mol/L), or incu bated with ACEI (10 -5 mol/L) and ET-1 (10 -7 mol/L) for different time (0, 6, 12, 24, 48 h), the levels of ALDO and AngⅡin the media were detecte d by radioimmunoassay.Results (1) Both ALDO and AngⅡat a basic quantity were produced by HKC c ells without any stimulants. After stimulation with ET-1, the production of AL DO and AngⅡwas increased with a dose and time dependant manner. When the HKC c ells were incubated with 10 -9 and 10 -7 mol/L ET-1 for 48 h, the lev els of ALDO and AngⅡwere significantly higher than those with 0 mol/L ET-1 ( P<0.05 or P<0.01). When the HKC cells were incubated with10 -7 mol /L ET-1 in different time, the levels of ALDO and AngⅡin 12, 24 and 48 h w ere significantly higher than those in 0 h(P<0.05 or P<0.01). (2) whe n the HKC cells were incubated with 10 -7 mol/L ET-1 and ACEI in different concentration for 48 h, the production of AngⅡand ALDO was significantly decre ased in 10 -9, 10 -7 and 10 -5 mol/L ACEI (vs 0 mol/L ACEI, P <0.01). Although the AngⅡproduction was completely blocked by these concentra tion of ACEI (vs the basic quantity of AngⅡ, P>0.05), the ALDO production was not (vs the basic quantity of ALDO, P<0.05). When the HKC cells were i ncubated with 10 -7 mol/L ET-1 and 10 -5 mol/L ACEI for different tim e, the production of AngⅡand ALDO was completely blocked in 6 h and 12 h (vs 0h , P>0.05). Although the AngⅡproduction was still completely blocked in 24 h and 48 h (vs 0 h, P>0.05), the ALDO production was not (vs 0 h, P<0 .05).Conclusion Local aldosterone can be synthesized by human renal proximal tubular cells. Its production can be up-regulated by ET-1. This effect is partially mediated by AngⅡ.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2005年第1期58-61,共4页
National Medical Journal of China
