The Mechanism of Calorie Restriction on Glucose Metabolism Indicators in GDM Rats
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摘要:
目的 研究热量限制对妊娠糖尿病（gestational diabetes mellitus，GDM）大鼠糖代谢指标及对子代脂质代谢受损的作用机制。 方法 45只大鼠随机分为健康组（健康大鼠）、模型组（GDM模型大鼠）、治疗组（GDM模型大鼠进行热量限制干预），每组15只，酶联免疫吸附法检测糖代谢指标及氧化应激指标；全自动生化分析仪检测血脂水平；苏木精-伊红染色观察大鼠胰腺组织病理学变化。领取45只子代小鼠，分为健康组子代组、模型组子代组及治疗组子代组，每组20只，采用全自动生化分析仪检测血脂水平；免疫印迹检测胰腺组织蛋白表达。 结果 与健康组相比，模型组大鼠胰岛素抵抗指数（homeostatic modelAssessment of insulin resistance，HOMA-IR）、空腹血糖、空腹胰岛素、总胆固醇（ total cholesterol，TC） 、三酰甘油（ triacylglycerol，TG） 、低密度脂蛋白胆固醇（ low density lipoprotein cholesterol，LDL-C） 、核因子E2相关因子2（nuclear factor erythroid-2 related factor 2，Nrf2）和血红素加氧酶-1（hemeoxygenase-1，HO-1）升高，高密度脂蛋白胆固醇（ high density lipopro- tein cholesterol，HDL-C） 降低（P < 0.05）；在经过热量干预后治疗组HOMA-IR、空腹血糖、空腹胰岛素、TC、TG、LDL-C、Nrf2、HO-1水平降低，HDL-C升高（P < 0.05）。与健康组相比，模型组超氧化物歧化酶（superoxide dismutase，SOD）、谷胱甘肽过氧化物酶（glutathione peroxidase，GSH-Px）降低（P < 0.05），丙二醛（malondialdehyde，MDA）升高（P < 0.05），与模型组相比，治疗组SOD、GSH-Px升高，MDA降低（P < 0.05）。与健康组子代相比，模型组子代小鼠TC、TG、LDL-C升高，HDL-C降低（P < 0.05）。与模型组子代相比，治疗组子代小鼠TC、TG、LDL-C降低，HDL-C升高（P < 0.05）。 结论 热量限制可改善GDM大鼠糖代谢及脂质代谢水平，降低胰腺组织病理损伤，其作用机制可能与激活Nrf2/HO-1信号通路有关。 Abstract:Objective To investigate the effect of calorie restriction on glucose metabolism in pregnant rats with Gestational diabetes mellitus （GDM） and the mechanism of impaired lipid metabolism in their offspring. Methods 45 healthy SD rats were randomly divided into the healthy group, the GDM model group, and the treatment group respectively with 15 in each group, and the rats in the GDM model were subjected to the calorie restriction intervention. The indicators of glucose metabolism and oxidative stress were detected by enzyme-linked immunosorbent assay and the blood lipid levels were detected by the fully automatic biochemical analyzer. Hematoxylin-eosin staining was used to observe the histopathological changes of pancreatic tissue in rats. Meanwhile, 45 offspring mice were collected and divided into the healthy offspring group, the model offspring group and the treatment offspring group respectively, with 15 in each group. The blood lipid levels were detected by an automatic biochemical analyzer. Western blotting was used to detect the protein expression in pancreatic tissue. Results Compared with the healthy group, the model group showed the increases in the Homeostatic Model Assessment of Insulin Resistance （HOMA-IR）, fasting blood glucose, fasting insulin, total cholesterol （TC）, triacylglycerol （TG）, low density lipoprotein cholesterol Elevated LDL-C, nuclear factor erythroid-2 related factor 2 （Nrf2） hemeoxygenase-1 （HO-1） levels, and a decrease in high density lipoprotein cholesterol （HDL-C） level （P < 0.05）; After the calorie intervention, the treatment group showed the decreases in HOMA-IR, fasting blood glucose, fasting insulin, TC, TG, LDL-C, Nrf2 and HO-1 levels, and an increase in HDL-C level （P < 0.05）. Compared with the healthy group, the model group showed the decreases in the Superoxide dismutase （SOD） and Glutathione peroxidase （GSH-Px） levels, and an increase in Malondialdehyde （MDA） level. Compared with the model group, SOD and GSH-Px in the treatment group increased, while MDA decreased （P < 0.05）. Compared with the offspring of the healthy group, the offspring mice in the model group showed the increases in the TC, TG and LDL-C levels in, and a decrease in the HDL-C level （P < 0.05）. Compared with the offspring of the model group, the offspring mice in the treatment group showed the decrease in the TC, TG and LDL-C of levels, and an increase in the HDL-C （P < 0.05）. Conclusion Calorie restriction can improve the levels of glucose metabolism and lipid metabolism in GDM rats and reduce the pathological damage of pancreatic tissue. The mechanism of action may be related to the activation of the Nrf2/HO-1 signaling pathway. -
图 1 苏木精-伊红染色结果（标尺为25 μm，×400）
A：健康组；B：模型组；C：治疗组。
Figure 1. Hematoxylin-eosin staining results （25 μm，×400）
图 3 各组子代小鼠胰腺组织 Nrf2/HO-1 蛋白水平比较（$\bar x \pm s $）
与健康组相比，*P < 0.05；与模拟组相比，#P < 0.05。
Figure 3. Comparison of Nrf2/HO-1 protein levels in pancreatic tissues of each group of offspring mice （$\bar x \pm s $）
表 1 各组大鼠糖代谢指标比较（$ \bar x \pm s $）
Table 1. Comparison of glucose metabolism indicators in each group of rats （$ \bar x \pm s $）
组别 n 空腹血糖（mmol/L） 空腹胰岛素（mIU/L） HOMA-IR 早期 中期 后期 早期 中期 后期 早期 中期 后期 健康组 15 4.72 ± 0.69 4.65 ± 1.23 4.72 ± 1.30 9.20 ± 1.26 9.34 ± 1.55 9.23 ± 2.00 2.16 ± 0.21 2.18 ± 0.65 2.06 ± 0.88 模型组 15 18.34 ± 3.26* 22.80 ± 3.27* 24.45 ± 4.10* 17.30 ± 3.04* 22.44 ± 3.07* 24.87 ± 3.96* 9.66 ± 2.00* 20.81 ± 4.76* 29.34 ± 5.70* 治疗组 15 14.89 ± 2.85*# 16.33 ± 2.38*# 18.34 ± 2.88*# 13.08 ± 2.55*# 18.77 ± 1.75*# 21.06 ± 3.64*# 5.84 ± 1.85*# 14.28 ± 2.35*# 21.02 ± 3.66*# F 132.700 213.100 164.000 73.940 138.000 69.840 96.490 140.600 152.800 P < 0.001△ < 0.001△ < 0.001△ < 0.001△ < 0.001△ < 0.001△ < 0.001△ < 0.001△ < 0.001△ 与健康组相比，*P < 0.05；与模型组相比，#P < 0.05；△P < 0.05。 
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表 2 各组大鼠脂质代谢水平比较[（$ \bar x \pm s $），mmol/L]
Table 2. Comparison of lipid metabolism levels in each group of rats [（$ \bar x \pm s $），mmol/L]
组别 n TC TG 早期 中期 后期 早期 中期 后期 健康组 15 2.01 ± 0.30 2.08 ± 0.45 2.11 ± 0.78 1.40 ± 0.20 1.45 ± 0.34 1.48 ± 0.36 模型组 15 3.66 ± 0.67* 6.77 ± 0.88* 8.69 ± 1.11* 2.50 ± 0.33* 4.72 ± 0.93* 5.90 ± 1.15* 治疗组 15 2.00 ± 0.34*# 3.39 ± 0.54*# 5.15 ± 1.03*# 1.29 ± 0.26*# 1.66 ± 0.47# 2.26 ± 0.66*# F 93.580 20.7.700 168.200 93.060 125.500 141.100 P < 0.001△ < 0.001△ < 0.001△ < 0.001△ < 0.001△ < 0.001△ 组别 n LDL-C HDL-C 早期 中期 后期 早期 中期 后期 健康组 15 0.51 ± 0.15 0.53 ± 0.14 0.59 ± 0.16 1.06 ± 0.19 1.04 ± 0.23 1.05 ± 0.17 模型组 15 1.88 ± 0.37* 2.45 ± 0.57* 3.80 ± 0.45* 0.77 ± 0.21* 0.60 ± 0.36* 0.38 ± 0.10* 治疗组 15 0.96 ± 0.20*# 1.23 ± 0.42*# 2.26 ± 0.37*# 0.99 ± 0.32*# 0.95 ± 0.22# 0.71 ± 0.13*# F 110.000 81.560 317.800 5.643 10.520 90.510 P < 0.001△ < 0.001△ < 0.001△ 0.006△ < 0.001△ < 0.001△ 与健康组相比，*P < 0.05；与模型组相比，#P < 0.05；△P < 0.05。
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表 3 各组大鼠SOD、MDA、GSH-pX水平比较（$ \bar x \pm s $）
Table 3. Comparison of SOD，MDA and GSH-pX levels in each group of rats（$ \bar x \pm s $）
组别 n SOD （U/mg） MDA （nmol/mg） GSH-pX （U/mg） 健康组 15 68.58 ± 10.00 10.08 ± 1.96 95.33 ± 18.04 模型组 15 30.15 ± 7.10* 36.05 ± 9.02* 43.08 ± 10.44* 治疗组 15 45.15 ± 8.30*# 25.44 ± 7.10*# 65.20 ± 14.06*# F 83.830 56.570 48.970 P < 0.001△ < 0.001△ < 0.001△ 与健康组相比，*P < 0.05；与模型组相比，#P < 0.05；△P < 0.05。
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表 4 各组子代小鼠脂质代谢比较[（$ \bar x \pm s $），mmol/L]
Table 4. comparison of lipid metabolism in each group of offspring mice [（$ \bar x \pm s $），mmol/L]
组别 n TC TG HDL-C LDL-C 健康组子代 20 5.18 ± 0.94 1.35 ± 0.26 1.25 ± 0.13 2.95 ± 0.24 模型组子代 20 6.24 ± 1.16* 2.24 ± 0.13* 0.54 ± 0.05* 4.05 ± 0.51* 治疗组子代 20 5.61 ± 0.42# 1.66 ± 0.17*# 0.96 ± 0.42*# 3.48 ± 0.26*# F 3.889 59.390 21.480 25.920 P < 0.001△ < 0.001△ < 0.001△ < 0.001△ 与健康组相比，*P < 0.05；与模型组相比，#P < 0.05；△P < 0.05。
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