姜黄素对2型糖尿病大鼠糖脂代谢及血清microRNA的影响

目的：探究姜黄素对2型糖尿病模型大鼠糖脂代谢影响的特点，并探讨其对糖尿病大鼠血清microRNA（miRNA）的影响。方法：将造模成功的2型糖尿病SD大鼠分为正常对照组、模型组、姜黄素低、中、高剂量组（剂量分别为50，150，250 mg·kg^-1），连续给药8周。每隔2周于给药前后测定空腹血糖（FBG）、餐后2 h血糖（2PBG）；给药前后测糖化血红蛋白水平（HbA1c）；8周末测血脂水平，并对血清中7个miRNA分子的表达量进行检测，以期探讨姜黄素对糖尿病大鼠降血糖的机制。结果：给药8周内，模型组FBG和2PBG值不断升高。姜黄素对糖尿病大鼠FBG和2PBG的显著影响在4周后出现。高剂量组FBG水平在给药4周后开始显著低于模型组（P<0.05），在给药6周后和8周后所有姜黄素剂量组的FBG水平均显著低于模型组（P<0.01）；在给药4周后3个姜黄素治疗组中2PBG水平明显下降，与模型组比较均有统计学意义（P<0.01）。给药8周后，模型组大鼠HbA1c水平显著高于正常对照组，姜黄素中、高剂量组的HbA1c水平显著低于模型组（P<0.05），低剂量组HbA1c水平较模型组降低，但无统计学意义；给药8周后，姜黄素各剂量组对TC水平均较模型组明显降低（P<0.01）；姜黄素中、高剂量组对TG水平较模型组明显降低（P<0.01）；姜黄素中、高剂量组对LDL-C水平较模型组也明显降低（P<0.01，P<0.05）；姜黄素组HDL-C水平有一定的升高，但只有高剂量组与模型组比较具有统计学意义（P<0.05）。姜黄素可显著降低模型组大鼠血清中7种miRNAs的表达水平（P<0.01），以高剂量组效果更加明显。结论：姜黄素给药8周后能够显著降低2型糖尿病大鼠空腹血糖和餐后血糖水平；并明显改善2型糖尿病大鼠的HbA1c的水平和血脂异常；并对糖尿病大鼠血清中7种miRNAs具有调节作用。

Effect of curcumin on glycolipid metabolism and microRNA in rats with type 2 diabetes mellitus

OBJECTIVE To explore the characteristics of glycolipid metabolism in type 2 diabetic rats treated with curcumin, and to explore its effect on serum microRNA (miRNA) in diabetic rats. METHODS The rats were fed with high fat and sugar diet before and after injection of streptozotocin for 4 weeks to establish diabetic models. After being fed with curcumin by different levels at 50, 150 and 250 mg·kg^-1 for 8 weeks, fasting blood glucose and postprandial plasma glucose were tested at week 0, 2, 4, 6 and 8. TC, TG, HDLC and LDLC were detected at week 8. The plasma level of HbAlc was measured at week 0 and 8. The expressions of seven microRNAs were evaluated at week 8. RESULTS During drug dosing for eight weeks, FBG and 2PBG values of model group increased. The significant effect of curcumin on FBG and 2PBG appeared after the fourth week. FBG level in the high dose curcumin group was significantly lower than that of model group in the fourth week (P<0.05). In the sixth week and eighth week, FBG levels of all curcumin dose groups were significantly lower than that of model group (P<0.01). After the fourth week, 2PBG levels of three curcumin treated groups were significantly lower than that of model group (P<0.01). The plasma level of HbAlc in model group was significantly higher than that of control group (P<0.05). The high curcumin dose group was significantly lower than that of model group after the treatment. Eight-week treatment with curcumin significantly decreased TC levels in the model group (P<0.01). The high dose curcumin group had significantly lower TG level compared with model group (P<0.01). LDLC levels of two dose groups were significantly reduced as compared with model group (P<0.05 or 0.01). Curcumin groups had certainly increased HDLC levels, but only the high dose group had significant difference compared with model group (P<0.05). Curcumin significantly reduced serum levels of expression of seven miRNAs in the model group, particularly in high dose group. CONCLUSION Curcumin administered for 8 weeks can significantly reduce fasting glucose and postprandial glucose in type 2 diabetic rats, significantly decrease plasma level of HbAlc and alleviate blood lipid disorders. It also has a regulatory role on seven miRNAs in diabetic rats.