|
|
Triptolide prolonged allogeneic islet graft survival in chemically induced and spontaneously diabetic mice without impairment of islet function |
Ming-Jun Xin, Shi-Hua Cui, Shuang Liu, Hai-Chen Sun, Fei Li, Jia-Bang Sun and Bin Luo |
Beijing, China
Author Affiliations: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China (Xin MJ, Cui SH, Liu S, Sun HC, Li F, Sun JB and Luo B); Department of Hepatobiliary Surgery, Qingdao Municiple Hospital, Qingdao 266011, China (Xin MJ); Department of Surgery, Shougang Hospital, Clinical School of Peking University, Beijing 100144, China (Cui SH)
Corresponding Author: Bin Luo, MD, Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China (Tel: 86- 10-83198857; Fax: 86-10-83154745; Email: binluobj@sina.com) |
|
|
Abstract BACKGROUND: 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.
METHODS: 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 naïve BALB/c group, and at 2, 4, 6, and 8 weeks in the syngeneic transplanted group.
RESULTS: 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.
CONCLUSION: TPT prolonged islets allograft survival in a chemically induced diabetic or an autoimmune diabetic murine model without impairment of islet function.
|
|
|
|
|
Cite this article: |
Xin MJ,
Cui SH,
Liu S,
et al.
Triptolide prolonged allogeneic islet graft survival in chemically induced and spontaneously diabetic mice without impairment of islet function.
Hepatobiliary Pancreat Dis Int
2010;
9(3):
312-318. DOI:
|
|
|
|
URL: |
http://dx.doi.org/ OR http://www.hbpdint.com/EN/Y2010/V9/I3/312 |
|
|
|