脂质体包埋Cl_2MDP和生理盐水负荷预防大鼠胰岛移植物无功能

Prevention of islet primary nonfunction with LE-CL_2MDP and normal saline loading in rats

目的 观察脂质体包埋氯甲双磷酸盐 (LE Cl2 MDP)和生理盐水负荷对大鼠胰岛移植物无功能 (PNF)的预防作用。方法 建立链脲霉素诱导的大鼠糖尿病模型。采用胶原酶消化法分离胰岛并移植到左肾被膜下。用LE Cl2 MDP预处理胰岛 ,术后 0d、1d ,受者腹腔内注射 15 0 μl·10g- 1 的LE Cl2 MDP并给予生理盐水负荷。根据血糖值判定胰岛移植物的功能 ,ED1免疫组化染色判定LE Cl2 MDP对巨噬细胞的清除效果。采用ELISA法测定血浆TNF α浓度。结果 经LE Cl2 MDP和生理盐水负荷处理后 ,胰岛移植物PNF的发生率较对照组显著降低 (P <0 0 1) ,移植物内ED1阳性率也明显降低 (P <0 0 1) ,但移植物存活时间无改变。PNF发生时 ,血浆TNF α浓度无明显改变。结论 LE Cl2 MDP和生理盐水负荷可显著降低胰岛移植物PNF的发生率 ,但不能延长移植物的存活时间。巨噬细胞是引起胰岛移植物PNF的重要原因之一。

Objective To observe preventive effects of LE-CL 2MDP and normal saline loading on islet graft primary nonfunction(PNF) using rat islet transplant model. Methods Rats were made diabetic with streptozotocin. Islets were isolated by collagenase digestion and were transplanted under the left kidney capsule. Pretreated islets with LE-CL 2MDP, and post-operation(days 0、1) recipients were injected intraperitoneal with LE-CL 2MDP at dose 150 μl·10 g -1 and were given the normal Saline loading at the same time. Judged islet graft function with blood glucose level. Effect of LE-Cl 2MDP on macrophage elimination was judged by ED 1 immunohistochemistry staining. Plasma TNF-α level was measured with ELISA assay. Results After treatment with LE-CL2MDP and normal Saline loading, the rate of islet graft PNF was significantly lower than the control group(P<0.01), and ED 1 positive rate of graft was lower too(P<0.01), but graft survival was not extended. Plasma TNF-α level was not significantly changed when PNF occurred. Conclusion LE-CL 2MDP and normal Saline loading can significantly reduce the rate of islet graft PNF, but can not prolong graft survival. Macrophages are the major cause of islet graft PNF.