高血压病气虚血瘀证患者血清诱导血管内皮细胞凋亡的效应及其机制研究

Hypertension and Qi Deficiency Blood Stasis(QDBS) syndrome are closely related to apoptosis. In the past research, we found that serum from patients with Hypertension's QDBS syndrome can cause vascular endothelial cells' injury, and the injury was closely related to apoptosis, existed β-tubulin expression change. The past research point that cytoskeletal change is the basis of apoptosis morphology change. Apoptosis is regulated by caspase-3 and other related proteins and genes, is regulated by some miRNAs too. For Confirming that serum from patients with Hypertension's QDBS syndrome can induct vascular endothelial cells' apoptosis, and Clarifying its' mechanism, in the basis of past work, we will use serum from patients with hypertension's QDBS syndrome affect cultured human umbilical vein endothelial cell(HUVEC) line, Observe endothelial cells' apoptosis, β-tubulin and apoptotic signal transduction related protein expression and distribution, apoptosis-related genes and miRNAs expression, simultaneously observed Bu Yang Huan Wu Decoction intervention effect. The study will further reveal the hypertension's QDBS syndrome substance; provide experimental basis for the prevention and treatment of hypertension's QDBS; In the same time, provide methodology reference for the research on traditional Chinese medicine syndromes' substance and 'Decoction Correlation to Syndrome' substance. It has important theoretical significance,clinical value and academic value.

高血压病及气虚血瘀证都与细胞凋亡密切相关。我们在以往的研究中，发现高血压病气虚血瘀证患者血清可以引起血管内皮细胞损伤，这种损伤与凋亡关系密切，并出现微管蛋白表达的改变。研究表明：细胞骨架的改变是细胞凋亡形态学改变的基础。细胞凋亡受caspase-3等相关蛋白及基因的调控，也受到miRNA的调控。为了证实高血压病气虚血瘀证患者血清可以诱导内皮细胞凋亡，并阐明其诱导凋亡的机制，我们在以往工作的基础上，以高血压病气虚血瘀证患者血清作用于培养的人脐静脉内皮细胞株，观察内皮细胞凋亡情况、β-微管蛋白和凋亡信号转导相关蛋白的表达和分布情况、凋亡相关基因、相关miRNAs表达情况，同时观察补阳还五汤的干预效应。该项研究，将进一步揭示高血压病气虚血瘀证的证侯实质；为高血压病气虚血瘀证的临床防治提供实验依据；同时，为证侯实质研究及"方证相关"的实质研究提供方法学借鉴。具有重要的理论意义、临床价值和学术价值。

高血压病及气虚血瘀证都与细胞凋亡密切相关。我们在以往的研究中，发现高血压病气虚血瘀证患者血清可以引起血管内皮细胞损伤，这种损伤与凋亡关系密切，并出现微管蛋白表达的改变。研究表明：细胞骨架的改变是细胞凋亡形态学改变的基础。细胞凋亡受caspase-3等相关蛋白及基因的调控，也受到miRNA的调控。为了证实高血压病气虚血瘀证患者血清可以诱导内皮细胞凋亡，并阐明其诱导凋亡的机制，我们在以往工作的基础上，以高血压病气虚血瘀证患者血清作用于培养的人脐静脉内皮细胞株，观察内皮细胞凋亡情况、β-微管蛋白和凋亡信号转导相关蛋白的表达和分布情况、凋亡相关基因、相关miRNAs表达情况，同时观察补阳还五汤的干预效应。结果发现：高血压病气虚血瘀证存在细胞凋亡及细胞核和细胞器的损伤，补阳还五汤具有一定的保护作用；高血压病气虚血瘀证患者血清可使内皮细胞分泌和表达Caspase-3、P53、β-actin、Fas、FasL、Bax、Bcl-2增高，补阳还五汤有抑制作用；高血压病气虚血瘀证患者血清可调节凋亡相关mRNAs和miRNAs表达，补阳还五汤可干预这一改变。该项研究，明确了高血压病气虚血瘀证患者血清诱导血管内皮细胞凋亡的效应，并阐明了其机制；也进一步揭示了高血压病气虚血瘀证的证侯实质，为高血压病气虚血瘀证的临床防治提供实验依据；同时，为证侯实质研究及“同病异证”、“方证相关”的实质研究提供了方法学借鉴。具有重要的理论意义、临床价值和学术价值。