ABSTRACT

Objective: This study aimed to investigate whether the antihypertensive effect of irbesartan (IRB) in spontaneously hypertensive rats (SHR) was achieved through improvement of insulin resistance and adjustment of the LPN–APN imbalance.Methods:SHR rats were divided into SHAM, SHR-A and SHR-I group(8 per group). Homologous Wistar–Kyoto (WKY) rats were used as control group (WKY).The SHR-I group received 30 mg/kg/d IRB, the SHR-A group received 2.5 mg/kg AML. After 8 weeks, systolic blood pressure (SBP) was measured. The concentrations of blood glucose, insulin, LPN and APN were detected. Rat epididymal adipose tissues were collected to analyze the mRNA expression levels ofepididymal LPN and APN using reverse transcription–polymerase chain reaction. In addition, the LPN/APN ratio was calculated. Results:SBP, homeostasis model assessment of insulin resistance (HOMA-IR), LPN concentration, adipose LPN mRNA expression level, and the LPN/APN ratio increased (P<0.05) and APN concentration and adipose APN mRNA expression level decreased (P<0.05) in SHR rats.IRB decreased SBP, HOMA-IR, serum LPN, adipose LPN mRNA expression, and the LPN/APN ratio and increased serum APN and adipose APN mRNA expression. Conclusion: The antihypertensive effect of IRB in SHR rats was associated with its improvement of insulin resistance and correction of the LPN–APN imbalance.

Abbreviations: ANOVA, one-way analysis of variance; SHR, Spontaneously hypertensive rats; WKY, Wistar kyoto rats; IRB, Irbesartan; AML, Amlodipine; LPN, Leptin; APN, Adiponectin; Ang-II, AngiotensinⅡ; HOMA-IR, Homoeostasis model assessment-insulin resistance; SBP, Systolic blood pressure; RT-PCR, Reverse transcription polymerase chain reaction; ARB, AngiotensinⅡreceptor blocker

摘要

目的：本研究旨在探讨厄贝沙坦（IRB）对自发性高血压大鼠（SHR）的降压作用是否是通过改善胰岛素抵抗和调节LPN-APN失衡来实现的。方法：将SHR大鼠分为SHAM、SHR- A和SHR-I组（每组8个）。同源Wistar-Kyoto（WKY）大鼠作为对照组（WKY）。SHR-I组接受30 mg/kg/d IRB，SHR-A组接受2.5 mg/kg AML。8 周后，测量收缩压 (SBP)。检测血糖、胰岛素、LPN和APN的浓度。收集大鼠附睾脂肪组织，采用逆转录-聚合酶链反应分析附睾LPN和APN的mRNA表达水平。此外，还计算了 LPN/APN 比率。结果：收缩压，P <0.05），SHR大鼠APN浓度和脂肪APN mRNA表达水平降低（P <0.05）。IRB降低SBP、HOMA-IR、血清LPN、脂肪LPN mRNA表达和LPN/APN比值，增加血清APN和脂肪 APN mRNA 表达。结论：IRB 对 SHR 大鼠的降压作用与其改善胰岛素抵抗和纠正 LPN-APN 失衡有关。

缩写： ANOVA，单向方差分析；SHR，自发性高血压大鼠；WKY，Wistar 京都大鼠；IRB，厄贝沙坦；AML，氨氯地平；LPN，瘦素；APN，脂联素；Ang-II，血管紧张素Ⅱ；HOMA-IR，稳态模型评估-胰岛素抵抗；SBP，收缩压；RT-PCR，逆转录聚合酶链反应；ARB, 血管紧张素Ⅱ受体阻滞剂