Nabi Fazul, Shahzad Muhammad, Liu Jingying, Li Kun, Han Zhaoqing, Zhang Ding, Iqbal Muhammad Kashif, Li Jiakui
a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.
b Faculty of Veterinary and Animal Sciences , Lasbela University of Agriculture, Water and Marine Sciences , Uthal , Balochistan , Pakistan.
Avian Pathol. 2016;45(2):187-93. doi: 10.1080/03079457.2016.1141170.
Tibial dyschondroplasia (TD) is an important long bone defect of broiler chickens that disturbs the proximal growth plate and is characterized by non-vascularized cartilage, a distended growth plate and lameness. Celastrol, a medicinal root extract from the plant Tripterygium wilfordii, is reported widely as a well-known heat-shock protein 90 (Hsp90) inhibitor. Recently, Hsp90 inhibition in chondrocyte differentiation and growth-plate vascularization were effective in restoring the morphology of the growth plate. The present study was aimed at investigating Hsp90 inhibition in TD using celastrol. The broiler chicks were divided into three groups; Control; TD induced (40 mg/kg thiram) and celastrol treatment. Hsp90, vascular endothelial growth factor and Flk-1 expressions were evaluated by quantitative real-time polymerase chain reaction and the protein levels of Hsp90 were measured by Western blot analysis. Antioxidant enzymes were determined to assess the liver damage caused by thiram and the protective effects of the medicine were evaluated by levels of serum biomarkers. The expression levels of Hsp90 and vascular endothelial growth factor mRNA transcripts were increased while Flk-1 receptor was decreased in TD-affected chicks. Celastrol therapy inhibited Hsp90 mRNA and protein levels and up-regulated the expressions of receptor Flk-1 in TD-affected tibial growth plates significantly (P < 0.05) in addition to rectifying the damaging effects of thiram on the liver by decreasing the levels of aspartate aminotransferase, alanine aminotransferase and malondialdehyde and correcting the oxidative imbalance. In conclusion, administering celastrol to dyschondroplastic chicks prevented un-vascularized growth plate, lameness and reinstated angiogenesis. Celastrol may be efficacious for the treatment of TD through the inhibition of Hsp90 expression and limiting the liver damage caused by thiram in broiler chickens.
胫骨软骨发育不良（TD）是肉鸡重要的长骨缺陷，会干扰近端生长板，其特征为无血管化软骨、生长板扩张和跛行。雷公藤红素是从植物雷公藤中提取的药用根提取物，作为一种著名的热休克蛋白90（Hsp90）抑制剂被广泛报道。最近，抑制Hsp90对软骨细胞分化和生长板血管化有效，可恢复生长板形态。本研究旨在探讨用雷公藤红素抑制TD中的Hsp90。将肉鸡分为三组：对照组；诱导TD组（40mg/kg福美双）和雷公藤红素治疗组。通过定量实时聚合酶链反应评估Hsp90、血管内皮生长因子和Flk-1的表达，并通过蛋白质印迹分析测量Hsp90的蛋白水平。测定抗氧化酶以评估福美双对肝脏造成的损伤，并通过血清生物标志物水平评估药物的保护作用。在受TD影响的雏鸡中，Hsp90和血管内皮生长因子mRNA转录物的表达水平升高，而Flk-1受体减少。雷公藤红素治疗除了通过降低天冬氨酸转氨酶、丙氨酸转氨酶和丙二醛水平并纠正氧化失衡来纠正福美双对肝脏的损害作用外，还显著抑制了受TD影响的胫骨生长板中Hsp90 mRNA和蛋白水平，并上调了受体Flk-1的表达（P<0.05）。总之，给患软骨发育不良的雏鸡施用雷公藤红素可防止生长板无血管化、跛行并恢复血管生成。雷公藤红素可能通过抑制Hsp90表达和限制福美双对肉鸡肝脏造成的损害而有效治疗TD。
