原发性高血压大鼠醛固酮与血管重构关系及依普利酮的治疗作用

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目的观察原发性高血压大鼠(spontaneously hypertensiverats,SHR)血管重构与醛固酮的关系以及依普利酮的治疗作用。方法22只16周龄雄性SHR随机分为依普利酮治疗组[SHR-Epl组,n=11,100mg(/Kg.d)灌胃]和未治疗组(SHR组,n=11),WistarKyoto大鼠为正常对照组(n=12),SHR组和对照组同体积蒸馏水灌胃,共10周。采用放射免疫法检测血浆醛固酮和经反相高效液相提纯肠系膜动脉离体灌注液中血管组织醛固酮;取胸降主动脉和肠系膜上动脉制成石蜡切片,行Masson染色和HE染色,测量两动脉中膜厚度(MT)、中膜横截面积(MCSA)、中膜细胞平均核面积(MNA),分析血管重构指标与醛固酮水平的相关性。结果SHR-Epl组和SHR组血浆及血管组织醛固酮均高于对照组(P<0.05),且SHR-Epl组血浆醛固酮高于SHR组(P<0.01),而血管组织醛固酮低于SHR组(P<0.01)。SHR-Epl组和SHR组胸降主动脉和肠系膜上动脉MT、MCSA和MNA均高于对照组(P<0.01),并且SHR-Epl组低于SHR组(P<0.01)。胸降主动脉及肠系膜上动脉MT、MCSA、MNA与血浆醛固酮无相关,但与血管组织醛固酮呈正相关(r>0,P<0.01)。结论26周龄SHR大鼠血浆和血管组织醛固酮均升高,血管组织醛固酮水平的升高可能是加重血管重构的原因之一。依普利酮治疗可以降低血管组织醛固酮水平,改善血管重构。 Objective To observe the relationship between vascular remodeling and aldosterone in spontaneously hypertensive rats (SHR) and the therapeutic effect of eplerenone. Methods Twenty-two male SHRs at 16 weeks of age were randomly divided into two groups: eplerenone treatment group [SHR-Epl group, n = 11 and 100 mg / kg · g intragastrically] and untreated group (n = 11) Rats were normal control group (n = 12), SHR group and control group with the same volume of distilled water for 10 weeks. The plasma aldosterone and the aldosterone in the perfusion fluid of mesenteric artery isolated by RP-HPLC were detected by radioimmunoassay. Paraffin sections were made by descending thoracic aorta and superior mesenteric artery. Masson staining and HE staining were used to measure the changes of both arteries (MT), mesothelial cell area (MCSA) and mean mesangial cell area (MNA). The correlation between vascular remodeling and aldosterone level was analyzed. Results The levels of plasma aldosterone and plasma aldosterone in SHR-Epl group and SHR group were significantly higher than those in control group (P <0.05), and the levels of plasma aldosterone in SHR-Epl group were higher than those in SHR group (P <0.01) P <0.01). The levels of MT, MCSA and MNA in the ascending descending aorta and superior mesenteric artery in SHR-Epl group and SHR group were significantly higher than those in control group (P <0.01), and those in SHR-Epl group were lower than those in SHR group (P <0.01). The descending thoracic aorta and superior mesenteric artery MT, MCSA, MNA had no correlation with plasma aldosterone, but had positive correlation with aldosterone (r> 0, P <0.01). Conclusions The aldosterone level in plasma and vascular tissue of 26-week-old SHR rats is increased. Elevated levels of aldosterone in vascular tissue may be one of the causes of exacerbation of vascular remodeling. Eplerenone treatment can reduce the level of aldosterone in vascular tissue and improve vascular remodeling.
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