雌激素与血浆同型半胱氨酸的交互作用对H型高血压的影响和血管内皮损伤的机制研究

The world health organization (WHO) predicts that by 2020, no communicable diseases are major causes of premature death in China ,and account for 79% of all cause of premature death. Cardiovascular and cerebrovascular disease is the primary causes of premature death in no communicable diseases. Hypertension is the primary risk factor which causes cardiovascular diseases and cerebrovascular diseases. In recent years, lots of researches showed that elevated homocysteine levels is a risk factor which causes the essential hypertension, maybe an independent risk factor. Hypertension accompanied by elevated homocysteine levels is called “H” hypertension, which means that patients suffer from double hazards both hypertension and elevated homocysteine.Hypertension accompanied by elevated homocysteine levelsv will be more danger to cause cardiovascular disease and cerebrovascular diseases, so far as to cause stroke, myocardial infarction, a higher risk of disability and death. Three fourths of hypertensions accompanied by elevated homocysteine levels in adult of China. Studies suggest that estrogen regulate metabolism of HCY, reduce homocysteine level and protect heart blood-vessel and head blood-vessel. Lowering estrogen levels can promote the occurrence and development of high blood pressure,but the mechanism in the body isn’t clarified. This study propose to use case-control study method in women of period of duration and animal experiment and cell experiment by using H type hypertension female castrated rats model in order to make clear of the correlation between estrogen and HCY levels. This study will clarify the interaction between estrogen and homocysteine ,which how to affect H type hypertension and understand the mechanism of damaging to vascular endothlial function.

据世界卫生组织预测，至2020年，非传染性疾病将占我国死亡原因的79%，其中心脑血管病将占首位，而高血压是引起心脑血管疾病的首要危险因子，大量研究认为血浆同型半胱氨酸（ HCY）是引发原发性高血压的危险因素之一,也是心脑血管疾病的独立危险因子。伴有血浆同型 半胱氨酸（HCY）水平升高的原发性高血压被定义为H型高血压，H型高血压对心脑血管的危害意味着高血压和高同型半胱氨酸的双重危害，我国成年人高血压中约75%伴有HCY水平升高。有研究提示女性雌激素具有调节HCY代谢，降低HCY，保护心脑血管的作用，雌激素水平的降低促进了高血压的发生和发展，但作用机制都还不明确，本研究拟通过采取人群病例对照研究方法和采用H型高血压雌性去势大鼠模型进行动物实验和细胞实验探讨雌激素和HCY水平之间的相关性，明确雌激素与HCY交互作用对H型高血压的影响以及对血管内皮功能损伤的作用机制。

【背景】H型高血压是伴有血浆同型半胱氨酸（Hcy）水平升高的原发性高血压。我国成年人高血压中约75%伴有Hcy水平升高。血浆Hcy是原发性高血压的危险因素，Hcy可以损伤血管内皮，高血压和Hcy水平升高都是心脑血管疾病危险因素。本课题组前期的国家自然科学基金项目研究结果显示：男性H型高血压的患病率明显高于女性，且高血压患者中男性的Hcy水平也高于女性，但女性绝经后Hcy水平与同龄男性无差异，Hcy水平随着年龄的变化而发生改变。有研究显示：雌激素水平的升高会降低高血压的发生和发展。Hcy水平变化是否与雌激素水平相关？是否Hcy与雌激素交互作用影响血压，并改善血管内皮功能？没有研究数据显示。课题组开展雌激素与Hcy交互作用对血压影响以及影响血管内皮细胞的机制研究。.【目的】探讨H型高血压的影响因素，了解雌激素和Hcy水平之间的相关性，明确雌激素与Hcy交互作用对H型高血压的影响以及对血管内皮功能损伤的作用机制，为H型高血压的防治提供理论依据。.【方法】通过开展人群病例对照研究分析人群水平雌激素、Hcy等因素与H型高血压之间的关系；通过建立H型高血压雌性大鼠模型，探索雌激素对血管内皮功能的作用机制；利用人脐静脉内皮细胞开展细胞实验，探索雌激素对Hcy及低切应力损伤对内皮c的作用机制。.【结果】研究结果表明LogVLDL、TG/HDL–C、BMI、WC、WHtR、WHR水平和高尿酸血症是H型高血压的独立危险因素。高蛋氨酸饮食导致的HHCY可引起大鼠血压升高，而雌二醇和依那普利叶酸片对H型高血压具有相同的治疗效果。雌二醇17β通过上调人脐静脉内皮细胞中CBS和CSE的表达，促进硫化氢的产生，从而抑制同型半胱氨酸介导的损伤。雌激素通过NF-KB通路抑制高剪切应力导致的炎症作用。研究表明雌激素可以调节Hcy代谢，降低血浆Hcy水平。.【结论】雌激素缺乏会引起机体HCY水平升高，而雌激素通过上调内皮细胞中CBS和CBE的表达促进硫化氢的产生及上调VCAM-1表达抑制同型半胱氨酸介导的损伤。