血管紧张素Ⅱ及氯沙坦对小鼠足细胞葡萄糖转运蛋白4表达的影响

摘要

Objective To investigate the influence of angiotensinⅡ(AngⅡ) on the expression of GLUT4 and whether losartan (Lo) could depress the function of AngⅡon podocytes. Methods The mouse podocyte clone 5 (MPC5) were divided into five groups: the control group, AngⅡ at the concentration of 10-6, 10-8, 10-10 mmol/L groups, and Lo 10-6 mmol/L+AngⅡ10-6 mmol/L group. The GLUT4 mRNA level was detected by semi-quantitative RT-PCR and the expression of GLUT4 by indirect immunofluorescence. Results Compared to the control group, in group AngⅡ10-6 mmol/L, the GLUT4 expression and protein synthesis were significantly decreased, GLUT4 mRNA transcription was decreased by 56.1%(P=0.041), and indirect immunofluorescence expression was decreased by 54.9%. The GLUT4 expression of AngⅡ10-10 mmol/L and AngⅡ10-8 mmol/L group was decreased compared with the control group, but there were no statistically significant difference. AngⅡ10-8 mmol/L depressed more GLUT4 expression than the AngⅡ10-10 mmol/L did, and there were also no statistically significant difference (P>0.05). As for the Lo 10-6 mmol/L+AngⅡ10-6 mmol/L group, the GLUT4 expression was significantly increased, when compared with the AngⅡ10-6 group its GLUT4 mRNA transcription was increased by 176.3%(P=0.006), and indirect immunofluorescence expres-sion increased by 87.8%(P<0.05). Conclusion AngⅡcould significantly decrease the GLUT4 expression and synthe-sis, and the effect was concentration dependent therefore could be hampered by Losartan.%目的：观察血管紧张素Ⅱ(AngiotensinⅡ，AngⅡ)对足细胞葡萄糖转运蛋白4(GLUT4)表达的影响，及血管紧张素1型受体阻断剂氯沙坦(Losartan，Lo)能否抑制AngII对足细胞GLUT4的作用。方法将小鼠MPC5足细胞分成对照组、AngⅡ10-6 mmol/L组、AngⅡ10-8 mmol/L组、AngⅡ10-10 mmol/L组、Lo10-6 mmol/L+AngⅡ10-6 mmol/L组，半定量聚合酶链反应(RT-PCR)检测足细胞GLUT4mRNA的水平，间接免疫荧光检测GLUT4蛋白的表达。结果与对照组相比，AngⅡ10-6 mmol/L组能够显著抑制GLUT4的表达及蛋白合成，GLUT4 mRNA的表达下降了56.1%(P=0.041)，间接免疫荧光表达下降了54.9%(P<0.05)。AngⅡ10-8 mmol/L组及AngⅡ10-10 mmol/L组GLUT4的表达与对照组相比有所下降，但差异无统计学意义(P>0.05)，AngⅡ10-8 mmol/L组对GLUT4抑制强于AngⅡ10-10 mmol/L组，两组间差异无统计学意义(P>0.05)。Lo 10-6 mmol/L+AngⅡ10-6 mmol/L组GLUT4的表达显著升高，与AngⅡ10-6组相比，mRNA升高176.3%(P=0.006)，蛋白表达升高87.8%(P<0.05)。结论 AngⅡ能够显著抑制足细胞GLUT4的表达及合成，具有浓度依赖性，这种作用能被氯沙坦所阻断。