1,6二-磷酸果糖减轻STZ致大鼠胰岛细胞凋亡

Mechanism of alleviation of STZ induced pancreatic islets apoptosis by fructose-1,6-disphosphate

目的探讨1,6二-磷酸果糖(FDP)对链脲佐菌素(STZ)致胰岛细胞凋亡的保护作用与血红素加氧酶/一氧化碳(HO-1/CO)、抗氧化以及NOS/NO系统的关系。方法用离体培养乳鼠胰岛细胞,分别检测STZ、FDP作用后细胞形态、细胞活性、细胞凋亡率、细胞HO-1的活性和细胞培养上清液中胰岛素的基础和高糖刺激分泌量以及CO的含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-PX)、诱生型一氧化氮合酶(iNOS)和NO的变化。结果STZ作用后,胰岛细胞活性降低,基础和高糖刺激胰岛素分泌减少,胰岛细胞凋亡率明显增加(P<0.01);细胞HO-1活性有所下降,上清液中CO生成减少(P<0.01),SOD、GSH-PX活性水平降低、iNOS增多、NO增加。与FDP孵育后细胞活性显著升高,胰岛素基础和高糖分泌量增多,胰岛凋亡率明显降低,HO-1活性和CO生成明显提高(P<0.01或P<0.05),同时SOD、GSH-PX活性水平明显增强、iNOS活性降低、NO生成减少,并且具有剂量依赖性。结论FDP能显著改善STZ致胰岛细胞凋亡,其机制可能与增加HO-1/CO系统水平,提高抗氧化酶SOD、GSH-PX的活性以及降低iNOS活性,从而减少NO的生成等途径有关。

Objective To investigate the protective role of FDP to STZ induced islest apoptosis and the potential mechanisms. Methods The pancreases of the rats were treated to collect islets cells. The cells were incubated with STZ with/or FDP. Cell morphology, insulin secretion, HO-1 activity, CO content, SOD activity, GSH-px activity, iNOS activity were examined. No conetent and apoptotic percentage was detected. Results HO-1 activity and CO content of the normal control group were low. STZ induced a significant decrease of cell activity and insulin release, flow cytometry analysis showed that apoptotie percentage of islet cells remarkably increased following the addition of STZ, FDP obviously improved the islets cellular activity damaged by STZ, basic amount of insulin secretion and stimulated by high glucose were improved （P 〈 0. 01 ）. Content of CO, activity of HO-1, SOD activity, GSH-PX activity were lower in the STZ group than the normal control group（P 〈0. 01 ）. The conetent were significantly higher in the STZ group than in the FDP group. Activities of HO-1 and content of CO were higher than in the STZ group. Conclusion FDP can alleviate STZ induced apoptosis of cultured 13 cells, the mechanism may be the improved HO-1 activity and increased CO content, improved SOD activity, GSH-px activity and decreased iNOS activity and NO content.