清道夫受体B1（SRB1）通过调控血小板活性介导血管紧张素II诱导高血压心脏损伤的机制研究

Hypertension is the first risk factor in cardiovascular and cerebrovascular diseases. Hypertension induces cardiac hypertrophy and cardiac fibrosis, leading to heart failure. The inflammatory microenvironment is the basis of hypertensive heart injury. The activated platelets trigger the inflammation. Scavenger receptor class B type 1 (SRB1) is a receptor of high-density lipoprotein, encoded by Scarb1 gene, involved in reverse cholesterol transport. However, its role is controversial in cardiovascular related diseases. It has been reported that a large number of SRB1 were expressed on platelets and regulate platelet activity, but the mechanism is still unclear. Our previous study found that Scarb1 deficient, which increased platelet activation, aggravated cardiac inflammation and remodeling in hypertension. Therefore, the hypothesis is SRB1 inhibited the cardiac inflammatory response and remodeling by regulating platelet activity. This study intends to adopt the wild type and Scarb1 knockout mice, infusion angiotensin II induced hypertensive cardiac injury. We used the methods of flow cytometry, pathology and molecular biology, proves SRB1 inhibits platelet activation and decreases the heart damage. We also used the experiment of bone marrow transplantation to illustrate the mechanism of SRB1 regulating platelet activity. Our objective is that to reveal a new theoretical basis for the prevention and treatment of hypertensive heart injury.

高血压是心脑血管疾病发生的第一位危险因素。高血压诱发心肌肥厚和纤维化，导致心力衰竭发生。高血压心脏损伤的基础是炎症微环境作用，而血小板活化是炎症反应的触发因素。清道夫受体B1（SRB1）是高密度脂蛋白受体，由Scarb1基因编码，参与胆固醇逆转运，其在心血管相关疾病中作用存在争议。有研究发现血小板表达大量SRB1，调控血小板活性，但作用机制仍不清楚。我们前期研究发现， Scarb1缺失小鼠活化的血小板增加，高血压心脏炎症和重塑加重。因此我们提出假设：SRB1通过调控血小板活性，抑制心脏炎症反应及重塑过程。本课题拟采用野生型和Scarb1基因敲除小鼠，建立血管紧张素II灌注诱导高血压心脏损伤模型，通过病理、流式细胞学、分子生物学等方法，明确SRB1抑制血小板活性，减轻高血压心脏损伤。通过骨髓交互移植实验，明确SRB1调控血小板活性的机制，从而为高血压心脏损伤的防治提供新的理论依据。

高血压是心脑血管疾病发生的第一位危险因素。高血压诱发心肌肥厚和纤维化，导致心力衰竭发生。高血压心脏损伤的基础是炎症微环境作用，而血小板活化是炎症反应的触发因素。清道夫受体B1(SRB1)是高密度脂蛋白受体，由Scarb1基因编码，参与胆固醇逆转运，其在心血管相关疾病中作用存在争议。有研究发现血小板表达大量SRB1，调控血小板活性，但作用机制仍不清楚。我们研究采用野生型和Scarb1基因敲除小鼠，建立血管紧张素II灌注诱导高血压心脏损伤模型，通过病理染色、流式细胞学、ELISA、细胞粘附实验等方法，明确SRB1抑制血小板活性，抑制高血压导致心脏炎症反应，减轻心脏重构。通过骨髓交互移植实验，明确SRB1调控血小板活性的机制是血脂异常。本研究揭示了 Ang II 诱导的高血压心脏损伤中，SRBI 介导血小板活化在心脏早期炎症反应中发挥保护性作用的机制。并且针对血脂异常合并高血压疾病，干预血小板活化以改善临床预后，提供了科学理论依据。