Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Hepatobiliary Pancreat Dis Int. 2010 Jun;9(3):312-8.
Triptolide (TPT) is a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook. F. It exhibits potent immunosuppressive and anti-inflammatory properties. This study was undertaken to investigate its effects on prolongation of islet allograft survival in rodents. Additionally, we investigated whether TPT would be toxic to islet function in vivo.
We transplanted BALB/c islets to either chemically induced diabetic C57BL/6 mice or spontaneously diabetic nonobese diabetic (NOD) mice. TPT was injected within 2 weeks or continuously, until rejection, in the two combinations. Then, we evaluated the toxicity of TPT on islet function by daily injection to naive BALB/c or diabetic BALB/c that was cured by syngeneic islet transplantation under the kidney capsule. Mice injected with cyclosporine A (CsA) or vehicle served as controls. Intraperitoneal glucose tolerance tests (IPGTTs) performed at 4 and 8 weeks in the naive BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group.
The medium survival time of islets allograft from TPT treated C57BL/6 and NOD recipients were 28.5 days (range 24-30 days, n=10) and 33.0 days (range 15-47 days, n=6), respectively, and they were significantly different from those of the vehicle treated controls, which were 14.0 days (range 13-16 days, n=6) and 5.0 days (range 4-10 days, n=6), respectively (all P<0.0001). The IPGTT demonstrated that there was no difference between the TPT treated and vehicle treated groups, either in the normal or syngeneic transplanted islet BALB/c mice. However, CsA injection impaired islet function in both normal and syngeneic transplanted mice as early as 4 weeks.
TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function.
雷公藤红素（TPT）是一种从中国草药雷公藤中提取的二萜三环氧。它具有很强的免疫抑制和抗炎作用。本研究旨在探讨其对延长啮齿动物胰岛同种异体移植物存活的影响。此外，我们还研究了 TPT 是否对体内胰岛功能有毒性。
我们将 BALB/c 胰岛移植到化学诱导的糖尿病 C57BL/6 小鼠或自发性糖尿病非肥胖型糖尿病（NOD）小鼠中。在这两种组合中，TPT 在 2 周内或连续注射，直到排斥。然后，我们通过每日注射到天真的 BALB/c 或通过肾囊下同种异体胰岛移植治愈的糖尿病 BALB/c 来评估 TPT 对胰岛功能的毒性。用环孢素 A（CsA）或载体注射的小鼠作为对照。在天真的 BALB/c 组中，在第 4 周和第 8 周进行腹腔内葡萄糖耐量试验（IPGTT），在同种异体移植组中，在第 2、4、6 和 8 周进行。
用 TPT 治疗的 C57BL/6 和 NOD 受体的胰岛同种异体移植物的中位存活时间分别为 28.5 天（范围 24-30 天，n=10）和 33.0 天（范围 15-47 天，n=6），与载体治疗的对照组有显著差异，分别为 14.0 天（范围 13-16 天，n=6）和 5.0 天（范围 4-10 天，n=6）（均 P<0.0001）。IPGTT 表明，在正常或同种异体移植的胰岛 BALB/c 小鼠中，TPT 治疗组和载体治疗组之间没有差异。然而，CsA 注射早在 4 周时就损害了正常和同种异体移植的小鼠的胰岛功能。
TPT 延长了化学诱导性糖尿病或自身免疫性糖尿病小鼠模型中的胰岛同种异体移植物的存活期，而不损害胰岛功能。
