霉酚酸和FTY720对仔猪胰岛簇样细胞毒性的实验研究  

An Experimental Study on the Effects of MPA,FTY720 on Piglets Islet Function in Vitro

作　　者：马克强[1,2] 信明军[1,3] 王占春[3] 于江[3] 吴晓平[1] 许评[1,3] 

机构地区：[1]卫生部细胞移植重点实验室临床中心,山东青岛266011 [2]湖南省衡阳市中心医院肝胆外科,湖南衡阳421001 [3]青岛市市立医院肝胆胰外科,山东青岛266071

出　　处：《临床普外科电子杂志》2013年第2期14-18,共5页Journal of General Surgery for Clinicians(Electronic Version)

基　　金：国家自然科学基金项目;项目编号:81171466

摘　　要：目的研究不同浓度的霉酚酸和FTY720在体外对仔猪胰岛簇样细胞毒性的大小。方法采用机械消化方法获取仔猪胰岛簇样细胞团,体外培养5天后分别与不同浓度的霉酚酸和FTY720混合培养24小时,然后用酶联免疫法测定经药物作用后的胰岛细胞在低糖(2.7mmol/L)和高糖加茶碱(16.7mmol/L和10.0mmol/L)刺激下胰岛素释放量,并计算即刺激指数。结果对照组胰岛细胞在低糖和高糖刺激下胰岛素释放量分别为(0.09±0.01)μIU/30IEQ和(0.36±0.03)μIU/30IEQ,刺激指数为4.06±0.35。与对照组相比,在低糖刺激时,添加不同药物浓度的霉酚酸和FTY720胰岛素释放量均无明显下降。在高糖加茶碱刺激时,添加高浓度霉酚酸组胰岛素释放量明显下降(P<0.05),刺激指数亦明显下降,而添加中、低浓度组无明显下降(P>0.05);添加高浓度FTY720组胰岛素释放量明显下降(P<0.05),刺激指数也明显下降,添加中低浓度组无明显下降(P>0.05)。结论与对照组相比较,在体外高浓度霉酚酸和FTY720对仔猪胰岛细胞有明显毒性作用,而中、低浓度对仔猪胰岛细胞无明显毒性作用。胰岛移植后,选择免疫抑制方案应遵循低剂量原则。Objective To explore the effects of immunosuppressive agents, Mycophenolic acid (MPA), FTY720 at different concentrations on the function of piglets islets-like cluster cells(ICC) in vitro. Methods The isolated and purified islets were cultured for 5 days in vitro and then they were cultured together with the immunosuppressive agents,MPA and FTY720 at different concentrations for 24h. The insulin release value was detected using Elisa kit and stimulation index was calculated after stimulations by glucose at low (2.7mmol/L) and at high (16.7 mmol/L and 10.0mmol/L ) levels with Theophylline.Results The insulin release were respectively 0.09±0.01μIU/30IEQ at low glucose level and 0.36±0.03μIU/30IEQ at high glucose level in control group and stimulation index was 4.06±0.35.Insulin release value at different concentration of MPA and FTY720 did not obviously decrease at low glucose stimulation,insulin release value and stimulation index obviously decrease at high glucose stimulation,insulin release value did not obviously decrease at the group of low and middle glucose stimulation, insulin release value and stimulation index obviously decrease at the group of high glucose stimulation and insulin release value and stimulation index did not obviously decrease at the group of low and middle glucose stimulation compared with the control group.Conclusion The MPA and FTY720 with high concentrations have obviously toxicity effect,of which with the middle and low concentrations have no toxicity effect to piglets islets in vitro compared with the control group.Therefore it is important to choose low-dose immunosuppressive protocols for islets transplantation.

关 键 词：仔猪胰岛 免疫抑制剂 毒性试验 MPA FTY720 

分 类 号：R61[医药卫生—外科学] R65[医药卫生—临床医学]