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目的 研究果糖诱导高血压合并高胰岛素血症、胰岛素抵抗时内皮素 1(ET -1)及其受体 (ETA)、血管紧张素Ⅱ受体 1(AT1)的变化和人组织型激肽释放酶 (HK )基因的治疗作用。方法雄性Sprague -Dawley (SD)大鼠饮用 10 %果糖水诱导形成高血压和胰岛素抵抗动物模型后 ,静脉注入含HKcDNA的重组质粒 (pcDNA HK )。监测血压 ,血清胰岛素及血糖等。 2周时处死动物 ,测定脏器中HK的表达及ET 1、ETA和AT1的表达情况。结果 饮高果糖水 2周后 ,动物血压、血胰岛素水平明显高于正常饮水组 ,静脉注射pcDNA HK后第 3天即可明显降低果糖诱导高血压大鼠的血压 ,最大降压效应在导入基因后第 14天 (达 15mmHg) ,其降压效应持续 3周以上。HK基因导入后第 2周 ,HK治疗组动物ET 1、ETA及AT1明显低于对照组 ,与正常组接近。并且在血压下降的同时 ,血胰岛素浓度亦明显降低。结论 动物高果糖饮水可导致高血压及高胰岛素血症 ,其机理可能与ET 1、ETA和AT1表达增加有关 ,HK基因的导入可能通过降低血管ET 1、ETA和AT1表达而降低血压 ,并纠正高血压伴随的高胰岛素血症 ,结果提示HK基因治疗高血压病尤其是合并糖尿病或胰岛素对抗者的可行性
Objective To study the changes of endothelin-1 (ET-1) and its receptor (ETA) and angiotensin Ⅱ receptor 1 (AT1) in fructose-induced hypertension combined with hyperinsulinemia and insulin resistance, Therapeutic effect of enzyme (HK) gene. Methods Male Sprague-Dawley (SD) rats were induced with 10% fructose into water to induce hypertension and insulin resistance. The recombinant plasmid pcDNA HK containing HKcDNA was injected intravenously. Monitoring blood pressure, serum insulin and blood sugar. Animals were sacrificed at 2 weeks, and the expression of HK, ET 1, ETA and AT1 in organs were measured. Results After 2 weeks of drinking high fructose water, the blood pressure and blood insulin levels in animals were significantly higher than those in normal drinking water groups. The blood pressure of rats with fructose-induced hypertension was significantly decreased on the 3rd day after intravenous injection of pcDNA-HK. The maximum blood pressure- After 14 days (up to 15mmHg), its antihypertensive effect lasts more than 3 weeks. At 2 weeks after the HK gene was introduced, the ET 1, ETA and AT1 in the HK-treated group were significantly lower than those in the control group, which were close to those in the normal group. And blood pressure decreased at the same time, blood insulin levels also significantly reduced. Conclusions High fructose drinking water can cause hypertension and hyperinsulinemia. The possible mechanism may be related to the increased expression of ET 1, ETA and AT1. The introduction of HK gene may decrease the blood pressure by decreasing the expression of ET 1, ETA and AT1 in blood vessel and correct High blood pressure accompanied by hyperinsulinemia, the results suggest the feasibility of HK gene therapy for hypertension, especially with diabetes or insulin antagonists