Persantin 對脂多醣體誘導大鼠肝損傷之研究

Persantin 是一種非選擇性的phosphodiesterase (PDE) 抑制劑，常用於臨床上腎臟疾病的血管擴張劑、用以改善血小板功能以及腎絲球腎炎所造成的蛋白尿。截至目前為止，許多的研究都已證實PDE inhibitors 具有抗氧化與抗發炎的能力，而本研究主要是探討persantin是否具有抑制肝發炎的能力。本研究以persantin (5mg/kg 及25mg/kg) 每天餵食Sprague- Dawley (SD) 大白鼠，一週後以腹腔注射LPS (5mg/kg) 六小時誘導肝損傷。在血清生化值分析上，觀察到對於ALT、Blood urine nitrogen(BUN)、BUN/CRE 及三酸甘油脂都有明顯的抑制作用。另外以TBARsassay 加以分析脂質過氧化的程度，可觀察到當給予persantin 後可以有效降低脂質過氧化的程度。在肝臟的組織切片發現，餵食persantin組與誘導組相較下，肝門靜脈中白血球趨化及浸潤現象皆有明顯改善。進一步觀察肝臟蛋白表現，可以發現PI3K、NF-κB、MAPK(p38/ERK/JNK)、iNOS、IL-6 等與發炎相關蛋白與細胞激素大量增加，而在給予persantin 後皆有明顯的抑制現象。而在細胞實驗上，我們同樣發現在給予persantin 後，可以減少由LPS 所誘導的PI3K、MAPK、COX-2 及iNOS 的表現。由此我們推測persantin 減少LPS所造成的肝損傷，部分是透過脂溶性抗氧化作用而達成。

關鍵字

persantin ；脂多醣體；環氧化酵素-2 ；一氧化氮合成酵素

並列摘要

Persantin (dipyridamole), a non-selective phosphodiesterase (PDE)inhibitor, is used in several clinical and xperimental studies to inhibit atelet aggregation, induce coronary vasodilation and inhibit leukotriene 4 as well as O2- generation by PMN. Recently, increasing evidences howed that many PDE inhibitors had the ability to antioxidant and inhibited inflammatory cytokine production such as TNF-α and IL-6 in uman monocytes. In this study, we aimed to examine the effect of ersantin on anti-inflammation. First of all, SD rats were fed with ersantin (5 and 25mg/kg) by oral tube once a day for one week, and then 5mg/kgipopolysaccaride (LPS) was administrated for six hour to induce liver damage. The results showed that persantin possessed the abilities to improve liver and kidney injury, including the reduction of ALT, Blood urine nitrogen (BUN), BUN/CRE, and triglyceride. Persantin was also found to possess the ability to reduce lipid peroxidation in liver. In histopathological evalution of liver, persantin decreased LPS-induced liver injury. Further, in liver protein lysate, we found persantin can inhibit PI3K, MAPK (p38/ERK/JNK), NF-κB, iNOS, IL-6 induced by LPS. In vitro assay, we found that persantin can inhibit LPS-induced PI3K MAPK (p38/ERK/JNK), COX-2, iNOS. In conclusion, the result showed persantin can reduce LPS-induced liver damage, and the effects might partially be due to its ability on improving antioxidative condition.

並列關鍵字

persantin ； LPS ； COX-2 ； NOS

參考文獻

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Persantin 對脂多醣體誘導大鼠肝損傷之研究

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