肾素系统在胰岛素抵抗性高血压中作用的探讨

EVALUATION OF RENIN ANGIOTENSIN ALDOSTERONE SYSTEM IN INSULIN RESISTANT HYPERTENSION

目的：从肾素血管紧张素醛固酮系统（ＲＡＡＳ）角度初步探讨胰岛素抵抗（ＩＲ）时高血压及左室肥厚（ＬＶＨ）形成的可能机制。方法：以高蔗糖饲料喂养８周形成胰岛素抵抗高血压的大鼠（ＩＲＨＲ）（ｎ＝１３）和正常对照ＳＤ大鼠（ｎ＝１０）为研究对象，用放免技术测定了其循环和心肌组织ＲＡＡＳ各成分的变化。并了解其ＬＶＨ情况。结果：ＩＲＨＲ组血压、血清胰岛素（ＩＮＳ）、甘油三酯、醛固酮（ＡＬＤ）、左室相对质量、心肌组织肾素活性（ＲＡ）、血管紧张素Ⅱ（ＡｎｇⅡ）水平明显高于对照组；其胰岛素敏感性指数、血清高密度脂蛋白明显降低；其血浆ＲＡ、ＡｎｇⅡ与对照组相比无显著差异，光镜及电镜观察发现其左室心肌细胞明显肥大、间质胶原纤维明显增多。结论：高蔗糖饲料喂养ＳＤ大鼠可以形成胰岛素抵抗和高血压，并有脂质代谢紊乱。

Objective: To study the possible mechanisms by which insulin resistanceinduces hypertension and left ventricular hypertrophy from the aspect of renin-angiotensin-aldosterone system (RAAS). Methods: The insulin-resistant hypertensive rat (IRHR) model (n=13) was reproduced by feeding SD rats for 8 weeks on a high-sucrose chow. SD rats (n=10) were studied as a control group. The elements in RAAS in plasma and myocardium were measured by radioimmunoassay and morphological changes were investigated. Results: Blood pressure (Bp) in IRHR was higher than in control group. Serum insulin (INS), triglyceride, aldosterone(ALD),left ventricular relative mass, renin activity(RA), angiotensin Ⅱ (Ang Ⅱ) in myocardium were higher in IRHR than in control group. Serum high-density lipoprotein (HDL-C) was lower in IRHR. Plasma RA and Ang Ⅱ in IRHR were not statistically different from those in control group (P>0.05). Myocardial cellular hypertrophy and increased interstitial collagenous fibers were found in IRHR by optical microscopy and electronmicrograph. Conclusions: High-sucrose feeding can induce insulin resistance, hypertension and dyslipidemia in SD rats. Hypertension in IRHR is related to insulin resistance and compensatory hyperinsulinemia. In this model hyperinsulinemia may have no or short-term effect on the level of circulatory RA and Ang Ⅱ, but plasma ALD and myocardial RA, Ang Ⅱ, which may be increased by hyperinsulinemia, may be the important factors that maintain the long-term high blood pressure. The formation of left ventricular hypertrophy in IRHR may be not only due to high blood pressure, serum INS which is a direct proliferation-stimulating factor, but also to tissular RA, Ang Ⅱ which may be activated by hyperinsulinemia.