硫化對甲酚引起實驗動物血管滲漏的研究

A study on vascular leakage induced by p-cresyl sulfate in experimental animal

戴珮洋(Pei-Yang Tai)

指導教授 ： 陳世杰

高雄醫學大學/醫學院/醫學研究所/基礎醫學組/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00117

摘要

近年來的流行病學研究指出，除了癌症，心血管相關疾病是目前受矚目的健康問題之一。除了已知的心血管疾病因子外，最近研究發現親蛋白質腎毒滯留物硫化對甲酚p-cresyl sulfate (PCS)除了與慢性腎臟病的惡化有關外，也有研究指出 PCS 在血管內皮細胞損傷扮演非常重要的角色，但是 PCS 在血管疾病之致病機轉仍不甚清楚。此篇論文研究的主要目標是藉由動物實驗了解 PCS可能引起的血管病變研究。本實驗經由大鼠血管注射染劑 Evans Blue （EB）後，在大鼠的背部兩側皮膚注射不同濃度的 PCS 溶液，經過不同時間的作用，萃取出組織中血管滲漏出EB的濃度。實驗結果顯示，在注射 PCS 不同濃度 (0.4、2、10與50 ?慆ol/site)後，與對照組 (注射 saline)相較，其血管滲漏的程度具有顯著性差異。其中 PCS 濃度最高的組別，血管滲漏程度亦是最高。在相同PCS濃度分別注射後10、30與60分鐘的實驗結果發現，血管滲漏僅在高濃度具有時間效應。而在實驗過程中亦觀察到，高濃度的注射點具有白色圓點。再經由血管注射碳粒India ink後，如上的時間與濃度條件作用後，將組織包埋切片後觀察，結果顯示PCS 濃度越高其碳粒標記血管壁也越密集。而從形態學觀察得知，隨著PCS濃度越高，真皮組織被破壞的程度也變高。而血管間亦有紅血球滯留的情形產生。從以上的結果得知：暴露在 PCS 的時間越長，其滲漏程度就越高。以上實驗結果顯示局部暴露於高濃度PCS會引起血管失常(滲漏)。

關鍵字

親蛋白質腎毒滯留物 ； 硫化對甲酚 ； 發炎反應 ； 血管滲漏

並列摘要

Recent epidemiological studies have shown that, beside cancer, cardiovascular-related diseases are high-profile health issues in Taiwan. In addition to we known factors of cardiovascular disease, protein-bound uremic retention solutes are correlated with the worsening of chronic kidney disease. Recent studies indicate that p-cresyl sulfate (PCS) is associated with coronary artery disease and endothelial dysfunction. However, the role of PCS in patients with endothelial disease is still unclear. Therefore, the goal of the present studies is to investigate whether PCS plays a role in increased vascular leakage in animal studies. Vascular permeability changes were evaluated by means of EB assay and the India ink tracer techniques. Rats were intravenously injected with Evans blue (EB) or India ink followed by intradermal injections of PCS with different doses: 0, 0.4, 2, 10 and 50 ?慆ol/site.
The results of EB permeability assay showed that various doses of PCS induced vascular leakage. In time course experiments, the results showed high doses of PCS induced vascular leakage in time-dependant manner. In histology studies, white circular spots were found on injection points with high doses of PCS. The India ink tracer technique also demonstrated time-dependent increases of vascular labeling in the tissues examined. In tissue sections, the degree of dermis disruption was also correlated with PCS doses. These findings indicate that in situ exposure to high concentration of PCS may produce vascular dysfunction (leakage) in vivo.

並列關鍵字

p-cresyl sulfate ； vascular leakage ； vascular permeability

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