尿石素A对1型糖尿病小鼠血糖的影响及其机制

Effect of urolithin A on blood glucose in type 1 diabetic mice and its mechanism

目的观察尿石素A抗小鼠1型糖尿病作用及其可能的机制。方法雄性昆明小鼠腹腔注射低剂量链脲佐菌素(STZ)5次,建立1型糖尿病模型后分为糖尿病模型组(M),尿石素A干预组(UA),尿石素A和自噬抑制剂氯喹干预组(UA+CQ),另设正常对照组,每组10只。药物干预8周,给药期间检测饮水量、体质量、空腹血糖和口服糖耐量,实验结束后测定糖化血清蛋白(GSP),血清胰岛素(INS)、白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)水平,在光学显微镜下观察胰腺组织病理结构,透射电镜下观察胰腺组织超微结构。结果给药2、4、6、8周,UA组空腹血糖均低于模型组,差异均有统计学意义(P<0.05或P<0.01)。与模型组比较,UA组GSP、INS、IL-1β和TNF-α水平均显著降低(P<0.01)。UA组血糖值均低于模型组,在60、120 min差异具有统计学意义(P<0.05或P<0.05)。UA组小鼠胰岛尚小,但是形状已基本规则,胰岛与外分泌部界限比较清晰,胰岛细胞数目比模型组增多。透射电镜观察发现UA组小鼠胰腺超微结构损伤较少,可观察到已被降解的自噬空泡,而在糖尿病模型组和UA+CQ组小鼠的细胞中观察到更多包含未降解物的自噬泡。结论尿石素A对1型糖尿病小鼠有降糖、抗炎、改善胰岛和β细胞形态等抗糖尿病作用,其机制可能与激活细胞自噬有关。

Objective To observe the anti-diabetic effects of Urolithin A(UA) on type 1 diabetic mice, and to explore its action mechanism. Methods Male KM mice were injected with low dose streptozotocin(STZ) intraperitoneally to induced diabetes model, and then UA was administrated for 8 weeks. Water intake volume, body weight and fasting blood glucose and oral glucose tolerance were measured during the experimental period. Serum interleukin-1β(IL-1β), tumor necrosis factor α(TNF-α), insulin and glycosylated serum protein(GSP) were measured at the end of the experiment. Pathological changes of pancreas were observed with light microscopy, ultrastructural changes of pancreatic tissue was observed under transmission electron microscope. Results After 2, 4, 6 and 8 weeks of administration, fasting blood glucose in the UA group was lower than that in the model group, and the difference was statistically significant(P<0.05 or P<0.01). Compared with the model group, the levels of GSP, INS, IL-1β and TNF-α in the UA group were significantly lower(P<0.01). The blood glucose of the UA group was lower than that of the model group, and there was significant difference in 60 and 120 mins(P<0.05 or P<0.05). The pancreas islets in the UA group were small, but the shape of islets was basically regular. The boundary between islets and exocrine parts was clear. The number of islet cells in the UA group were more than that in the model group. Transmission electron microscopy showed that the ultrastructure of pancreas in the UA group was less damaged, and degraded autophagic vacuoles were observed. In the diabetic model group and UA+CQ group, more autophagic vacuoles containing undegraded substances were observed. Conclusion Urolithin A have hypoglycemic, anti-inflammatory effects, can improve pancreas islet and β cell morphology in type 1 diabetic mice, its mechanism may be related to the activation of autophagy.