Lee Jue Seong, Seo JungHyeok, Kim Sokho, Rahman Md Mahbubur, Shin Hong Ju
Department of Pediatrics, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea.
Department of Surgery, College of Veterinary Medicine, Jeonbuk National University, Iksan, Korea.
Korean Circ J. 2024 Jan;54(1):43-56. doi: 10.4070/kcj.2023.0120. Epub 2023 Sep 12.
The therapeutic strategy for inflammation and degenerative calcification is of utmost importance for bioprosthetic heart valve (BHV) implanted patients. The purpose of this study was to compare the anti-inflammatory and anti-calcification effects of Entelon150 (grape seed extract), losartan, and rosuvastatin, in a rabbit model of intravascular BHV leaflet implantation in bovine pericardium.
A total of 28 rabbits were implanted with BHV leaflet in the external jugular veins. The Entelon150 group was administered 7.7 mg/kg Entelon150 twice daily for 6 weeks after surgery. The losartan and rosuvastatin groups received 5.14 mg/kg and 1 mg/kg, respectively, once per day. The control group received 1 ml of saline once daily. And then, calcium concentration was measured in the implanted BHV, and histological and molecular analyses were performed on the surrounding tissues.
The calcium content of the implanted tissue in the Entelon150 group (0.013±0.004 mg/g) was lower than that in the control group (0.066±0.039 mg/g) (p=0.008). The losartan (0.024±0.016 mg/g, p=0.032) and rosuvastatin (0.022±0.011 mg/g, p=0.032) groups had lower calcium content than the control group, and higher tendency than the Entelon150 group. Immunohistochemistry revealed that the expressions of bone morphogenic protein 2 (BMP2), S-100, and angiotensin II type 1 receptor in the Entelon150 group showed lower tendency than those in the control group. The protein expression levels of BMP2 were reduced in the Entelon150 group compared with those in the control group.
Entelon150 exhibited a significant effect, similar to other drugs, in reducing calcification and inflammation in the intravascular bovine pericardium.
对于植入生物人工心脏瓣膜（BHV）的患者而言，炎症与退行性钙化的治疗策略至关重要。本研究旨在比较Entelon150（葡萄籽提取物）、氯沙坦和瑞舒伐他汀在牛心包血管内BHV瓣叶植入兔模型中的抗炎和抗钙化作用。
总共28只兔子在颈外静脉植入BHV瓣叶。Entelon150组在术后6周内每天两次给予7.7mg/kg Entelon150。氯沙坦组和瑞舒伐他汀组分别每天一次给予5.14mg/kg和1mg/kg。对照组每天给予1ml生理盐水。然后，测量植入的BHV中的钙浓度，并对周围组织进行组织学和分子分析。
Entelon150组植入组织的钙含量（0.013±0.004mg/g）低于对照组（0.066±0.039mg/g）（p=0.008）。氯沙坦组（0.024±0.016mg/g，p=0.032）和瑞舒伐他汀组（0.022±0.011mg/g，p=0.032）的钙含量低于对照组，且比Entelon150组有更高的趋势。免疫组织化学显示，Entelon150组中骨形态发生蛋白2（BMP2）、S-100和1型血管紧张素II受体的表达比对照组有降低的趋势。与对照组相比，Entelon150组中BMP2的蛋白表达水平降低。
Entelon150在减少血管内牛心包钙化和炎症方面表现出与其他药物相似的显著效果。
