[Effects of PM_(2.5) combined with high-fat and high-sugar diet on glucose metabolism and learning memory ability in rats]

To explore the effects of combined exposure to atmospheric PM_(2.5) and a high-fat and high-sugar diet on glucose metabolism and learning and memory abilities in rats.

Thirty-two 3-week-old SPF-grade Wistar rats, half male and half female, were randomly divided into four groups: the control group, the PM_(2.5) group, the high-fat and high-sugar group, and the high-fat and high-sugar + PM_(2.5) group, with 8 rats in each group. The control group and the PM_(2.5) group were fed with normal maintenance feed(total energy 14.23 kJ/g), while the high-fat and high-sugar group and the high-fat and high-sugar + PM_(2.5) group were fed with high-fat and high-sugar feed(total energy 19.80 kJ/g). The control group and the high-fat and high-sugar group were raised in a clean room for 24 weeks. After 16 weeks of raising, the high-fat and high-sugar group and the high-fat and high-sugar + PM_(2.5) group were exposed to PM_(2.5) using an online PM_(2.5) concentration and small animal whole-body exposure system. The PM_(2.5) exposure concentration was 8 times the real-time outdoor PM_(2.5) concentration, for 6 hours per day, 5 days per week, for a total of 8 weeks. The concentration during the exposure period was 177.20(48.53, 358.01) μg/m~3. The body weight of the rats was measured every 2 weeks. After 24 weeks of the experiment, the Morris water maze test was conducted to evaluate learning and memory abilities. The oral glucose tolerance test(OGTT) was used to calculate the area under the curve(AUC). The fasting blood glucose(FBG), fasting serum insulin(FINS), and glycosylated hemoglobin(HbA1c) levels of the rats were detected. The homeostasis model assessment for insulin resistance index(HOMA-IR) was calculated. The expression levels of glucose transporter 4(GLUT4) and phosphatidylinositol3-ki-nase(PI3K)/protein kinase B(AKT) signaling pathway-related proteins in the hippocampus of the rats were detected by Western blot.

The body weight of rats increased with the duration of exposure, but there was no statistically significant difference in body weight among the four groups at the same time point(P > 0.05). Compared with the control group(14.81±1.22) and the PM_(2.5) group(14.24±0.84), the AUC of the high-fat high-sugar group(16.26±0.86) and the high-fat high-sugar + PM_(2.5) group(16.44±1.99) was significantly increased, with statistical significance(P<0.05). Compared with the control group, the levels of FBG, FINS, HbA1c and HOMA-IR in the PM_(2.5) group, the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group were significantly increased(P<0.05). Compared with the PM_(2.5) group and the high-fat high-sugar group, the levels of FBG, FINS, HbA1c and HOMA-IR in the high-fat high-sugar + PM_(2.5) group were significantly increased(P<0.05). The escape latency of the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group was(11.11±2.69) s and(14.80±5.25) s, respectively, which was significantly higher than that of the control group(7.25±2.79) s(P<0.05). The number of times rats crossed the platform in the PM_(2.5) group, the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group was(4.38±1.19) times, (5.00±1.31) times and(3.38±1.69) times, respectively, which was significantly lower than that of the control group(8.25±1.67) times(P<0.05), and the high-fat high-sugar + PM_(2.5) group(3.38±1.69) times was lower than the high-fat high-sugar group(5.00±1.31) times(P<0.05). Compared with the control group, the expression of GLUT4, insulin receptor(IR), IRS1, P-PI3K and P-AKT proteins in the hippocampus of the rats in the PM_(2.5) group, the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group was down-regulated(P<0.05). Compared with the PM_(2.5) group, the expression of GLUT4, IR, IRS1 and P-PI3K proteins in the hippocampus of the rats in the high-fat high-sugar group and the high-fat high-sugar + PM_(2.5) group was down-regulated. Spearman correlation analysis showed that FBG, FINS, HbA1c and HOMA-IR were negatively correlated with the number of times rats crossed the platform(P<0.05), and AUC, HbA1c and FINS were positively correlated with the escape latency(P<0.05). The expression levels of proteins related to the IR/PI3K/AKT signaling pathway were positively correlated with the number of times rats crossed the platform(P<0.05).

Exposure to PM_(2.5) and a high-fat high-sugar diet can cause abnormal glucose metabolism and learning and memory impairment in rats, and the combined exposure of both further exacerbated these changes.