Effects of chlorogenic acid on glucose tolerance and its curve characteristics in high-fat diet-induced obesity rats
Received date: 2019-01-28
Online published: 2020-04-18
目的 观察绿原酸(chlorogenic acid,CGA)对高脂饲料诱导的肥胖(diet-induced-obesity,DIO)大鼠糖耐量及其曲线特征的作用, 为开发利用CGA早期预防和延缓糖尿病的发生提供依据.方法: 46只雄性Sprague-Dawley(SD)大鼠随机选择8只作为普通饲料组(normal control group,CON), 其余大鼠饲喂高脂饲料.4周后按标准筛选高脂诱导的肥胖大鼠24只并随机分为高脂饲料组(high fat diet group,HFD),50%(质量分数)CGA组和98%(质量分数)CGA组,每组8只,分别给予磷酸缓冲盐溶液(phosphate buffer saline,PBS),50%CGA和98%CGA灌胃8周,每周检测体质量,每4周进行一次口服糖耐量试验(oral glucose tolerance test,OGTT),实验期末检测空腹胰岛素及胰岛素释放,计算稳态模型胰岛素抵抗指数(homeostasis model assessment insulin resistance,HOMA-IR)和内脏脂肪百分比,苏木精和伊红(hematoxylin and eosin,HE)染色检测胰腺组织病理变化.结果: CGA干预前,与CON组相比,HFD组OGTT第120分时(OGTT-120min)血糖值(P<0.05)和葡萄糖曲线下面积(area under curve-glucose,AUC-G)(P<0.05)均显著升高;干预4周后葡萄糖峰值时间延迟(P<0.05);干预8周 HOMA-IR指数显著升高且OGTT-0min,OGTT-30min,OGTT-60min,OGTT-120min胰岛素水平和胰岛素曲线下面积(area under curve-insulin,AUC-I)显著升高(P<0.05), 胰腺胰岛显著增生(P<0.05).与HFD组相比,干预4周末,50%CGA和98%CGA组大鼠糖耐量及其葡萄糖峰值时间均无显著变化;干预8周后,50%CGA组大鼠OGTT-60min,OGTT-120min血糖值,HOMA-IR指数,OGTT-0min,OGTT-30min,OGTT-120min血清胰岛素水平显著降低(P<0.05);98%CGA组大鼠OGTT-60min,OGTT-120min血糖值,HOMA-IR指数,OGTT-0min,OGTT-120min血清胰岛素水平显著降低(P<0.05);50%和98%CGA组大鼠的葡萄糖峰值时间均显著前移(P<0.05), 胰岛异常增生改善(P<0.05).结论: OGTT葡萄糖峰值时间延迟是DIO大鼠糖耐量异常表现之一,50%和98%CGA均可改善DIO大鼠的糖耐量和葡萄糖峰值时间延迟.
关键词： 绿原酸; 肥胖; 糖耐量异常; OGTT葡萄糖峰值时间
郭成成 , 张晓圆 , 玉应香 , 谢岚 , 常翠青 . 绿原酸对高脂饲料诱导的肥胖大鼠糖耐量及其曲线特征的影响[J]. 北京大学学报（医学版）, 2020 , 52(2) : 269 -274 . DOI: 10.19723/j.issn.1671-167X.2020.02.012
Objective: To observe the effect of chlorogenic acid (chlorogenic acid,CGA) on the glucose tolerance and its curve characteristics in high fat diet-induced obesity (diet-induced-obesity,DIO) rats, so as to provide scientific grounds for the development and utilization of CGA in early prevention and reversal of prediabetes.Methods: Eight of forty-six male Sprague-Dawley rats were randomly selected as the normal diet group (CON group), and the rest were fed with high-fat diet. After 4 weeks, 24 high-fat-induced obese rats were screened according to the criteria and then randomly divided into high fat diet group (HFD group), 50% CGA group and 98% CGA group. The CGA groups received intragastric administrations of 50% CGA and 98% CGA orally via a gavage needle once a day for 8 weeks, respectively, while the CON and HFD groups received a carrier solution (phosphate buffer saline, PBS). Their body weights were measured weekly and oral glucose tolerance test (OGTT) was performed every 4 weeks. Fasting insulin and insulin release were measured at the end of the study. Meanwhile, HOMA-IR and visceral fat percentage were calculated. Histopathological examination by hematoxylin and eosin staining method were evaluated in the pancreatic tissues.Results: Before the intervention of chlorogenic acid, blood glucose levels 120 min after glucose loading (P<0.05) and AUC-G (P<0.05) were increased in the HFD group when compared with the CON group, and the time to glucose peak was delayed after 4 weeks of chlorogenic acid intervention (P<0.05). After 8 weeks of intervention, the HOMA-IR index, the insulin levels at 0 min, 30 min, 60 min, and 120 min after glucose loading and AUC-I increased (P<0.05), and the histopathological examination showed obvious hyperplasia of pancreatic islets (P<0.05). Compared with the HFD group, there was no significant change in glucose tolerance and glucose peak time in 50%CGA and 98%CGA groups at the end of 4 weeks of intervention. How-ever, after 8 weeks of intervention, OGTT-60min,OGTT-120min blood glucose (P<0.05) were lower, HOMA-IR index and OGTT-0min, OGTT-120min serum insulin level decreased (P<0.05), the time to glucose peak shifted to an earlier timepoint (P<0.05), abnormal islet hyperplasia attenuated (P<0.05) in 50% CGA and 98% CGA groups. Also, the OGTT-30min serum insulin level was decreased (P<0.05) in 50% CGA group.Conclusion: Delay in time to glucose peak during the OGTT was one of the manifestations of impaired glucose tolerance in DIO rats, and 50% and 98% CGA could improve the glucose tolerance and delay in glucose peak time.
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