摘要
目的 :探讨血管紧张素Ⅱ (AngⅡ )对近端肾小管上皮细胞DNA、RNA及蛋白质合成的作用。 方法 :采用3H标记的胸腺嘧啶核苷 (3HT)、3H标记的尿嘧啶核苷 (3HU)及3H标记的脯氨酸 (3HP)掺入的方法 ,观察AngⅡ对无血清培养的LLC PK1细胞DNA、RNA及蛋白质合成的作用。 结果 :AngⅡ刺激 2 4、48和 72h ,LLC PK1细胞3HT掺入与对照组相比无明显变化。AngⅡ刺激 48h ,3HU掺入的min-1值明显升高 (4 2 42± 6 6 9、4119± 5 71及3 972± 5 6 4vs 3 2 2 0± 2 6 5 ,10 -10 、10 -8及 10 -6mol/LvsControl,P <0 0 5 ) ;同样 ,3HP掺入的min-1值也有明显升高(6 2 0 72± 10 912、6 3 736± 92 11及 6 45 0 7± 15 5 90vs 492 40± 70 45 ,10 -10 、10 -8、及 10 -6mol/LvsControl,P <0 0 5 )。缬沙坦 (10 6mol/L)可以阻断AngⅡ刺激LLC PK13HU及3HP掺入的作用。 结论 :①AngⅡ可以刺激LLC PK1细胞RNA及蛋白质合成 ,而对LLC PK1细胞DNA合成无明显促进作用 ,表明AngⅡ可以诱导LLC PK1细胞肥大而不是增生。②血管紧张素Ⅱ 1型受体拮抗剂对AngⅡ诱导的LLC PK1细胞肥大有明显抑制作用。
Co mpensatory hypertrophy of nephron,es pecially the proximal convoluted tubule, is a classic theory in the mechanism of progression of chronic renal insufficiency.Many large prospective cl inical trails demonstrated that the inhi bition of angiotensin converting enzyme can slow the progression of chronic rena l failure.However,the exact role of angi otensin Ⅱ on the growth of renal tubular epithelial cells was not clear.In this study,we investigated the role of Ang Ⅱ and valsartan (Ang Ⅱ type 1 receptor ant agonist,AT1Ra)on the synthesis of DNA,RN A and protein by proximal tubular epithe lial cells. METHODOLOGY After incubated with Ang Ⅱ and / or AT1Ra(valsartan),the DAN,RNA and prot ein synthesis of LLC-PK1 cells(procine t ubular epithelial cells line)were measur ed with 3H-thymidine, 3H-uridine an d 3H-proline incorporation to evaluate the proliferation and hypertrophy of the se cells. RESULTS Measured by 3H-thymidine incorpora tion in LLC-PK1 cells at 24,48 and 72 ho urs,there was no obseved effect of Ang Ⅱ (10 -10 、10 -8and 10 -6mol/L)on the prolife ration of LLC-PK1 cells.In contrast,the same concentration of Ang Ⅱ could promot e 3H-uridine and 3H-proline incorpor ation in LLC-PK1 cells.Incubated with LL C-PK1 cells for 48 hours,Ang Ⅱ(10 -10、 10 -8and 10 -6mol/L)could increase t he 3H-uridine incorporation (3 220±265 vs 4 242±669,4 119±571 and 3 972±564,Co ntr ol vs 10 -10、10 -8and 10 -6mol/L ,P<0.05).This effect was blocked by valsartan(10 -6mol/L)(3 100±450 vs 4 242±669、2 984±482 vs 4 119±571 and 2 985±701 vs 3 972±564,P<0.05).Simila rly,in cubated with LLC-PK1 cells for 48 hours, Ang Ⅱ(10 -10、10 -8and 10 -6mol/L) increased the 3H-proline incorporat ion( 49 240±7 045 vs 62 072±10 912,63 7 36±9 211 and 64 507±15 590,control vs 10 -10,10 -8and 10 -6mol/L,P<0.0 5).This effect was blocked by valsart an(10 -6mol/L)(49 516±6 808 vs 62 07 2±10 912、50 901±7 241 vs 63 736±9 211 and 49 592±10 059 vs 64 507±15 590 res pectively,P<0.05). CONCLUSION Ang Ⅱ can stimulate RNA and protein but not D NA synthesis in LLC-PK1 cells,which impl ies that Ang Ⅱ can induce renal proxim al tubular epithelial cell hypertrophy b ut not proliferation.This hypertrophic e ffect can be inhibited by AT1Ra,which su ggests that this effect is mediated by Ang Ⅱ type 1 receptor.
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
2000年第5期416-419,共4页
Chinese Journal of Nephrology,Dialysis & Transplantation
