Triptolide as an Alternative to IVIG Therapy for Kawasaki Disease in a Mouse Model

Abstract

Background: Kawasaki disease is treated by immunoglobulin therapy, which has adverse side effects like renal damage. Aims: The aim of the present study was to explore the effectiveness of triptolide, a compound derived from threewingnut that has anti-inflammatory effects, on the treatment of Kawasaki disease in a mouse model. Study Design: Animal experiment. Methods: A mouse model of Kawasaki disease was established through exposure to Candida albicans by intraperitoneal injection. Exposed mice were then randomly divided into several groups (each n=15): model group (saline-treated), low- or high-dose triptolide groups (0.2 mg/kg or 0.4 mg/kg, respectively), and IVIG (high-dose immunoglobulin) group (1 g/kg body weight). Unexposed mice served as an additional control group. Nine weeks from the initial exposure, mice were euthanised and coronary tissues and blood samples were harvested. The rate of apoptosis was detected by TUNEL, and ICAM-1 expression was detected by immunohistochemistry in coronary endothelial cells. Serum TNF-α levels were detected by ELISA. Results: Compared to mice in the (unexposed) control group, apoptosis of endothelial cells, ICAM-1 expression, and serum TNF-α levels were significantly increased in all exposed mice (p<0.05), confirming the presence of disease. However, treatment with triptolide or IVIG significantly lowered these measures compared to untreated exposed mice (model group; p<0.05). Conclusions: Triptolide treatment reduces markers of coronary endothelial inflammation in a mouse model of Kawasaki disease, similar to IVIG treatment, and therefore may be a useful alternative therapy for this disease. Turkish Başlık: Kawasaki Hastalığı için Fare Modelinde IVIG Tedavisine Alternatif olarak Triptolid Tedavisi Anahtar Kelimeler: Triptolid, Kawasaki hastalığı, endotel hücreleri, apoptoz, ICAM-1, TNF-α Arka Plan: Kawasaki hastalığı, böbrek hasarı gibi olumsuz yan etkilere sahip immunoglobulin terapi ile tedavi edilmektedir. Amaç: Bu çalışmanın amacı, threewingnut adlı bitkiden türetilen ve anti-inflamatuar etkilere sahip bir bileşik olan triptolidin, Kawasaki hastalığının tedavisindeki etkinliğini fare modelinde araştırmaktı. Çalışma Tasarımı: Hayvan üzerinde deney. Yöntemler: İntraperitoneal Candida albicans enjeksiyonu ile Kawasaki hastalığının fare modeli oluşturuldu. Maruz bırakılan fareler daha sonra rasgele birkaç gruba ayrıldı (herbiri n=15): model grubu (salin ile muamele edilen), düşük veya yüksek doz triptolid grupları (sırasıyla 0.2 mg/kg veya 0.4 mg/kg) ve IVIG (yüksek doz immunoglobulin) grubu (1 g/kg vücut ağırlığı). Maruz bırakılmayan fareler ilave kontrol grubu olarak görev yaptı. İlk maruziyetten dokuz hafta sonra farelere ötenazi uygulandı ve koroner dokuları ve kan örnekleri alındı. Koroner endotel hücrelerinde apopitoz oranı TUNEL ile saptandı ve ICAM-1 ekspresyonu immunohistokimya ile saptandı. Serum TNF-α seviyeleri ELISA ile saptandı. Bulgular: Kontrol grubundaki farelere (maruz bırakılmamış) kıyasla, endotel hücrelerinin apopitozu, ICAM-1 ekspresyonu ve serum TNF-α seviyeleri maruz kalan tüm farelerde anlamlı şekilde artmıştı (p<0.05) ve bu da hastalık varlığını doğrulamaktaydı. Bununla birlikte triptolid veya IVIG tedavisi, maruz bırakılmış ve tedavi edilmemiş farelere kıyasla bu değerleri anlamlı şekilde düşürdü (model grubu; p<0.05). Sonuç: Triptolid tedavisi IVIG tedavisine benzer şekilde Kawasaki hastalığının fare modelinde koroner endoteliyal inflamasyonun belirteçlerini düşürmektedir ve dolayısıyla bu hastalık için yararlı bir alternatif tedavi olabilir.

Keywords

• Triptolide, Kawasaki disease, endothelial cells, apoptosis, ICAM-1, TNF-α

Triptolide as an Alternative to IVIG Therapy for Kawasaki Disease in a Mouse Model

Öz

Kaynakça

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