缬沙坦及红花对单侧输尿管结扎大鼠肾脏细胞增殖的影响

Effect of valsartan and safflower on cell proliferation in SD rat induced with unilateral ureteral obstruction

目的观察肾间质纤维化实验大鼠肾脏细胞增殖的特点及缬沙坦、红花对其的抑制作用。方法结扎大鼠单侧输尿管(UUO)复制肾间质纤维化实验动物模型,分别给以缬沙坦10mg·kg-1·d-1、红花4.0g·kg-1·d-1经口灌服,14d后摘取肾脏,采用免疫组化、RT-PCR检测增殖细胞核抗原(PCNA)的表达、流式细胞学检测细胞增殖/凋亡及细胞周期。结果免疫组化结果显示UUO大鼠肾脏PCNA阳性细胞表达明显增多,RT-PCR显示其基因表达增强,流式细胞学显示UUO大鼠肾脏细胞增殖/凋亡比例下降,S期细胞比例增多;缬沙坦及红花治疗组均可在蛋白及基因水平下调其表达。结论单侧输尿管结扎可诱导肾脏细胞增殖,血管紧张素受体拮抗剂缬沙坦及中药红花可下调其表达。

Aim To investigate the role of valsartan and safflower on cell proliferation in renal interstitial fibrosis rat. Method Renal interstitial fibrosis model was induced with unilateral ureteral obstruction（UUO） and treated with valsartan（ 10 mg ·kg^-1 · d^-1）, safflower （4. 0 g·kg^-1·d^-1） orally. The kidneys were got after 14 days and the proliferating cell nuclear antigen （PCNA） was determined with immunohistoehemistry and RT-PCR, cell apoptosis/proliferation and cell cycle were examined with flow cytometry. Results The PCNA positive cells increased markedly in UUO rat by immunohistochemical staining and up-regulated with RT-PCR. Flow cytometry showed that the ratio of apoptosis/proliferation was decreased because of the proliferating cell increased in S-stage. All of them were inhibited with valsartan and safflower. Conclusion UUO can induce the cells proliferating in kidney of rats, and valsartan and safflower have the role to downregulate its expression.