氯沙坦可减轻兔模型中高尿酸血症诱导的动脉粥样硬化。

Losartan alleviates hyperuricemia-induced atherosclerosis in a rabbit model.

作者信息

Zheng Hongchao, Li Ning, Ding Yueyou, Miao Peizhi

机构信息

Department of Cardiology, Xuhui District Central Hospital Shanghai, China.

出版信息

Int J Clin Exp Pathol. 2015 Sep 1;8(9):10428-35. eCollection 2015.

PMID:26617751

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4637566/

Abstract

OBJECTIVE

To investigate the mechanisms underlying the therapeutic effects of losartan on hyperuricemia-induced aortic atherosclerosis, in an experimental rabbit model.

METHODS

Male rabbits (n = 48) were divided into control, hyperuricemia (HU), hypercholesterolemia + hyperuricemia (HC + HU) and high-purine with 30-mg/kg/d losartan (HU + losartan) groups. Serum uric acid (UA) and plasma renin and angiotensin II activities were determined. Aortic tissue specimens were analyzed for histological changes and proliferating cell nuclear antigen (PCNA). Liver tissues were sampled for quantitative analyses of liver low-density lipoprotein receptor (LDLR) mRNA and protein via reverse transcription polymerase chain reaction and western blotting.

RESULTS

After 12 weeks, serum UA and plasma renin and plasma angiotensin II activities were enhanced in the HU and HU + HC groups (P < 0.001) compared to the control, whereas in the HU + losartan group plasma renin activity was not different and serum UA concentrations as well as plasma angiotensin II activity were moderately enhanced (P < 0.05). Smooth muscle cell (SMC) PCNA expression increased strongly in the HU and HU + HC groups (P < 0.001), but was less pronounced in the HU + losartan group. In contrast, transcription and expression of LDLR mRNA and protein were significantly higher in the control and HU + losartan groups compared to the HU and HU + HC groups. Both the HU and HU + HC groups had elevated intima thickness and intima areas compared to the control and HU + losartan groups.

CONCLUSIONS

Losartan can alleviate experimental atherosclerosis induced by hyperuricemia.

摘要

目的

在实验性兔模型中研究氯沙坦治疗高尿酸血症诱导的主动脉粥样硬化的潜在机制。

方法

将雄性兔（n = 48）分为对照组、高尿酸血症（HU）组、高胆固醇血症 + 高尿酸血症（HC + HU）组和给予30 mg/kg/d氯沙坦的高嘌呤组（HU + 氯沙坦）。测定血清尿酸（UA）、血浆肾素和血管紧张素II活性。分析主动脉组织标本的组织学变化和增殖细胞核抗原（PCNA）。采集肝脏组织，通过逆转录聚合酶链反应和蛋白质印迹法对肝脏低密度脂蛋白受体（LDLR）mRNA和蛋白质进行定量分析。

结果

12周后，与对照组相比，HU组和HU + HC组的血清UA、血浆肾素和血浆血管紧张素II活性增强（P < 0.001），而HU + 氯沙坦组的血浆肾素活性无差异，血清UA浓度和血浆血管紧张素II活性中度增强（P < 0.05）。HU组和HU + HC组的平滑肌细胞（SMC）PCNA表达强烈增加（P < 0.001），但在HU + 氯沙坦组中不明显。相反，与HU组和HU + HC组相比，对照组和HU + 氯沙坦组的LDLR mRNA和蛋白质的转录和表达显著更高。与对照组和HU + 氯沙坦组相比，HU组和HU + HC组的内膜厚度和内膜面积均增加。