哇巴因改善宫内生长受限子代大鼠的葡萄糖代谢的机制研究

The increased apoptosis and decreased proliferation of pancreatic beta cell during intrauterine growth restriction (IUGR) result in reduction of beta cell number, which significantly increases the risk of type 2 diabetes mellitus in adulthood. Ouabain partially restores the nephron number at birth through inhibiting the apoptosis and promoting the proliferation of the embryonic kidney during IUGR, which could normalize the nephric function and blood pressure in adulthood. Our previous study revealed that treatment with low doses of ouabain during pregnancy could improve the glucose metabolism of rat offspring with intrauterine growth restriction in adulthood. Thus, we propose that ouabain could rescue the development of the pancreatic beta cell and islet through inhibiting the apoptosis and promoting the proliferation of the pancreatic beta cell. We plan to study the effects of ouabain on beta cell during serum deprivation through cellular study, and evaluate the effect on the pancreatic incretory structure and function through animal research. This study will provide an alternative therapeutic drug for targeted rescuing pancreatic development of IUGR offspring.

胎儿宫内生长受限（IUGR）时胰腺β细胞凋亡增加、增殖降低，出生后β细胞数目下降，成年时2型糖尿病的发病风险明显上升。哇巴因在IUGR时通过抑制胎鼠肾脏细胞的凋亡、促进增殖，在出生时部分恢复子代的肾单位数目，使成年子代的肾功能和血压基本恢复正常。本项目组前期研究发现：孕期应用低剂量哇巴因可改善IUGR子代大鼠的葡萄糖代谢状况。因此，我们假设哇巴因可通过抑制胰腺β细胞的凋亡、促进增殖来挽救胰腺β细胞和胰岛的发育，从而改善成年期子代的葡萄糖代谢状况。本项目拟通过细胞实验研究血清缺乏时低剂量哇巴因对β细胞的影响，同时通过动物实验评估IUGR时应用低剂量哇巴因对胰腺内分泌结构及功能的影响。本项目的完成将为有针对性的挽救IUGR子代胰腺的发育提供一种可行的治疗药物。

胎儿宫内生长受限（IUGR）时胰腺β细胞凋亡增加、增殖降低，出生后β细胞数目下降，成年时2型糖尿病的发病风险明显上升。哇巴因在IUGR时通过抑制胎鼠肾脏细胞的凋亡、促进增殖，在出生时部分恢复子代的肾单位数目，使成年子代的肾功能和血压基本恢复正常。本项目组前期研究发现：孕期应用低剂量哇巴因可改善IUGR子代大鼠的葡萄糖代谢状况。因此，我们假设哇巴因可通过抑制胰腺β细胞的凋亡、促进增殖来挽救胰腺β细胞和胰岛的发育，从而改善成年期子代的葡萄糖代谢状况。本项目通过细胞实验研究血清缺乏时低剂量哇巴因对β细胞的影响，同时通过动物实验评估IUGR时应用低剂量哇巴因对胰腺内分泌结构及功能的影响。结果发现哇巴因确实可以在宫内生长受限时降低胰腺β细胞的凋亡，宫内生长受限的大鼠在胎儿期接受哇巴因干预后，其成年后患葡萄糖耐量受损的风险下降。本项目的完成将为有针对性的挽救IUGR子代胰腺的发育提供一种可行的治疗药物。