氨氯地平对SHR肾小球系膜细胞的保护作用

Protective Effect of Amlodipine on SHR Glomerular Mesangial cell

目的 观察氨氯地平是否能抑制SHR肾小球系膜细胞的肥大与增殖。将氨氯地平与苯那普利拉及氯沙坦比较其单用或合用时的不同效应。方法 采用SHR系膜细胞培养技术 ,以3H 亮氨酸或3H 胸苷的cpm值反映蛋白或DNA合成。结果 (1 )SHR系膜细胞在AngⅡ、PDGF刺激后引起的肥大与增殖 ,均可被氨氯地平所抑制 ;(2 )在AngⅡ组 ,对于肥大与增殖三种药物单用时抑制作用无差异。PDGF引发的肥大 ,氯沙坦、普那普利拉明显优于氨氯地平 ,且普那普利拉比氨氯地平强 ;PDGF引发的增殖 ,仅氯沙坦比氨氯地平强。 (3)氨氯地平与普那普利拉或氯沙坦联合后均有协同的抗肥大作用。抗增殖方面 ,氨氯地平与普那普利拉联合在AngⅡ组无协同作用 ,在PDGF组有协同作用。氨氯地平与氯沙坦配伍后对增殖有协同拮抗作用。结论 (1 )氨氯地平能抑制SHR系膜细胞的肥大与增殖。(2 )在AngⅡ组 ,抗系膜细胞的肥大与增殖 ,氨氯地平与普那普利拉、氯沙坦互相之间无差异 ;由PDGF引发的肥大与增殖 ,氯沙坦明显优于氨氯地平 ;(3)氨氯地平与普那普利拉或氯沙坦联合后有协同抗系膜细胞肥大作用 ;在抑制增殖方面 ,氨氯地平 +氯沙坦可能优于氨氯地平 +普那普利拉。

Objective To investigate the effect of CCB amlodipine on hypertrophy and proliferation in SHR mesangial cells. Methods Mesangial cells were cultured from SHR as previously described. 3H leucine or 3H thymidine was added to measure protein or DNA synthesis, induced by Ang Ⅱor PDGF. The inhibitory effects of amlodipine were compared with ACEI (Benazeprilat) and losartan.\ Results (1)Amlodipine significantly decreased protein and DNA synthesis in SHR mesangial cells stimulated by Ang Ⅱ and PDGF. (2) no significant differences in the inhibitory effect were found among these three drugs. In PDGF group, protein synthesis was most signi ficantly decreased by losartan, the effect of losartan and benazeprilat was stronger than amlodipine. DNA synthesis was sabstantially reduced by losartan than that by amlodipine. (3) Treat that of ment with amlodipine plus benazeprilat or losartan showed additiveinhibiting effect on protein synthysis. Combination of amlodipine and benazeprilat showed no additive inhibiting effect on the proliferation by Ang Ⅱ, but in PDGF group the combined effect was appeared. Amlodipine plus losartan demonstrated a more significant decrease in DNA synthesis. Conclusions (1) The hypertrophy and proliferation of SHR mesangial cell could be inhibited by amlodipine. (2) In AngⅡ group, no significant differences were found among these three drugs. In PDGF group, the inhibitory effect of losartan was stronger than amlodipine. (3) Combined with amlodipine and benazeprilat or losartan showed combined effect in decreasing protein synthesis. In proliferation, only amlodipine plus losartan demonstrated a significant combined effect.