17β-雌二醇增加卵巢切除大鼠心肌内皮型一氧化氮合酶的表达和一氧化氮生成(英文)

Study of 17 β -Estradiol supplementation on increasing eNOS expression and NO production in ovariectomized rat heart

目的 :观察 17β 雌二醇替代治疗对卵巢切除大鼠心肌组织中一氧化氮 (NO)和内皮源性一氧化氮合酶 (eNOS)的影响。方法 :成年雌性SD大鼠经双侧卵巢切除术 ,假手术组作为对照 ,术后 3周随机分为假手术组 ,模型对照组 ,17β 雌二醇(0 .1mg·kg-1·d-1)和溶媒 (芝麻油 )皮下注射治疗组 ,处理 6周 ,记录大鼠的血压、心率、子宫重量 ;检测血中雌二醇的含量 ;亚硝酸还原酶法检测心肌匀浆中NO含量 ;Westernblot分析心肌中eNOS及eNOS调节蛋白小凹蛋白 1(caveolin 1)的蛋白表达情况。结果 :17β 雌二醇治疗组的心率 (314± 16次 分 )较其他各组低 ,与溶媒对照组比较 ,雌二醇替代治疗组心肌匀浆中NO的含量增加一倍 ,eNOS蛋白表达明显增加 (P <0 .0 1) ,而作为eNOS的内源性抑制物caveolin 1的表达却明显减少 (P <0 .0 5 )。结论 :雌激素替代治疗直接增加卵巢切除大鼠心肌eNOS的表达量以及NO的产生 ,减少抑制eNOS活性的小凹蛋白 1表达。

AIM : To investigate whether 17 β -estradiol influences the production of nitric oxide (NO) and expression of eNOS in ovariectomized (OVX) rats heart. METHODS : Female mature Sprague-Dawley rats were subjected to a bilateral ovariectomy, and sham operation as control. OVX rats were randomly assigned to the following treatments: 17 β -estradiol (100 μg·kg -1 in 100 μl sesame oil sc daily), 17 β -estradiol vehicle (100 μl sesame oil sc daily) and OVX control. The treatment lasted 6 weeks. Blood pressure, heart rate, plasma estradiol, uterine weights and nitrite production in the myocardium were studied. Western blot analysis was used to assay the protein expression of eNOS and caveolin-1. RESULTS : The heat rates in 17 β -estradiol treatment group (314±16 beats·min -1) were lower than those in other groups ( P < 0.05). Compared with vehicle group, nitrite production increased one fold in the hearts of E 2 treatment group, the abundance of eNOS protein showed a significant increase ( P < 0.01). Concurrently caveolin-1 protein, an endogenous eNOS inhibitor, protein expression abundance was significantly decreased ( P < 0.05) in the E 2 supplement group. CONCLUSION : Estrogen supplementation directly increases eNOS functional activity and NO production in rat heart, this effect may be related to estrogen-induced deceasing of heart rates.