厄贝沙坦对自发性高血压大鼠瘦素、脂联素的影响

Effects of irbesartan on leptin and adiponectin in spontaneously hypertensive rats

目的 探讨血管紧张素Ⅱ受体拮抗剂（ARB）厄贝沙坦对自发性高血压大鼠（SHR）瘦素、脂联素的影响及可能机制.方法 24只雄性SHR大鼠随机分为SHR模型组（SHR-C）、SHR氢氯噻嗪组（SHR-H）和SHR厄贝沙坦组（SHR-I）,每组8只;另设同源雄性Wistar Kyoto（WKY）大鼠8只为对照组.SHR-I组应用厄贝沙坦30 mg·kg-1·d-1灌胃,SHR-H组应用氢氯噻嚷10 mg·kg-1·d-1灌胃,SHR-C和WKY组均配以等量蒸馏水灌胃,连续8周后,测尾动脉收缩压（SBP）;颈动脉取血,检测血清血糖、胰岛素、瘦素和脂联素浓度;取大鼠附睾脂肪组织,通过反转录和聚合酶链反应（RT-PCR）,分析附睾脂肪瘦素mRNA和脂联素mRNA表达水平.结果 与WKY组比较,SHR-C组大鼠收缩压显著升高（P＜0.01）;与SHR-C组比较,SHR-I组和SHR-H组大鼠收缩压显著降低（P＜0.01）.与WKY组比较,SHR-C组大鼠胰岛素抵抗指数（HOMA-IR）显著升高（P＜0.01）;与SHR-H组和SHR-C组比较,SHR-I组大鼠HOMA-IR明显降低（P＜0.05）.与WKY组比较,SHR-C组大鼠血清瘦素浓度和脂肪瘦素mRNA表达水平显著增高（P＜0.01）;与SHR-C组比较,SHR-I组大鼠血清瘦素浓度显著降低（P＜0.01）,脂肪瘦素mRNA表达水平明显降低（P＜0.05）.与WKY组比较,SHR-C组大鼠血清脂联素浓度和脂肪脂联素mRNA表达水平显著降低（P＜0.01）;与SHR-C组比较,SHR-I组大鼠血清脂联索浓度和脂肪脂联索mRNA表达水平显著升高（P＜0.01）.结论 厄贝沙坦能改善自发性高血压大鼠胰岛索的敏感性,减少其脂肪组织瘦素的合成和分泌,增加脂联素的合成和分泌.

Objective To investigate the effects of angiotensin 11 receptor antagonist irbesartan on leptin, adiponectin in spontaneously hypertensive rats and the possible mechanism. Methods 24 male SHR rats were randomly divided into SHR model group （SHR-C）,SHR hydrochlorothiazide group （SHR-H）and SHR irbesartan group（SHR-I）, eight each, and set eight homology male WKY rats as control group. The rats in SHR-I group were treated with 30 mg·kg^-1·d^-1 irbesartan. The rats in SHR-H group were treated with 10 mg·kg^-1·d^-1 hydrochlorothiazide. The rats in SHR-M and WKY group were treated with equivalence of dis- tilled water. After 8 weeks,measuring the tail artery systolic blood pressure in all rats. The concentration of glucose,insulin,leptin and adiponectin in the serum were assessed by radioimmunoassay. The expression level of leptin mRNA and adiponectin mRNA in epididymal adipose tissue were assessed by RT-PCR. Results Compared with the WKY group, SBP of the SHR-C group were significantly increased （P〈0.01）. Compared with the SHR-C group,SBP of the SHR-I group and the SHR-H group were significantly descended （P〈 0.01）. Compared with the WKY group,HOMA-IR of the SHR-C group were significantly increased （P〈 0.01）. Compared with the SHR-C group and the SHR-H group,HOMA-IR of the SHR-I group were signifi- cantly descended（P〈0.05）. Compared with the WKY group, serum leptin concentrations and expression levels of adipose tissue leptin mRNA of the SHR-C group were significantly increased（P〈0.O1 ）, and compared with the SHR-C group, serum leptin concentrations of SHR-I decreased significantly （P〈0.01）, expression levels of adipose tissue leptin mRNA of the SHR-I group were significantly lower （P〈0.05）. Compared with the WKY group,serum adiponectin concentrations and expression levels of adipose tissue adiponectin mRNA of the SHR-C group were significantly decreased （P〈0.01）, and compared with the SHR-C group,serum adiponectin concentrations and expression levels of adipose tissue adiponectin mRNA of SHR-I group were significantly increased （P〈0.01）. Conclusion Irbesartan can improve insulin sensitivity,reduce synthesis and secretion of leptin,increase synthesis and secretion of adiponectin in the spontaneously hypertensive rat.