Abstract：
OBJECTIVE: To investigate the effect of tea polyphenols(TP) on improving depression-like behavior in aged type 2 diabetes(T2DM) model rats.
METHODS: A total of 40 8-week-old SD male rats were randomly divided into the control group(n=10) and the modeling group(n=30) according to the body weight. The rats in the modeling group were fed with high-glucose and high-fat diet and treated with 50 mg/kg D-galactose by intraperitoneal injection daily until the end of the experiment, while the rats in the control group were fed with the standard diet and treated with an equal volume of saline by intraperitoneal injection. After 4 weeks, the rats in the modeling group were injected with 25 mg/kg STZ, meanwhile the rats in the control group were injected with an equal volume of citric acid buffer. The level of fasting blood glucose(FBG) was measured on the 14~(th) day. When FBG≥16.7 mmol/L, the rats were identified as successful model of the T2DM rats. Then, the model rats were randomly divided into the model group, 150, 300 mg/kg TP groups(n=10, respectively), and the rats were given intragastric intervention for 8 weeks. The levels of the FBG were detected, and the depression-like behavior of rats was assessed by the open field test(OFT) and forced swimming test(FST). The density of microglia in hippocampus CA1 region was assessed by immunofluorescence staining, and protein expressions of P53, Iba1, iNOS, Arg-1 and BDNF were determined by western blot.
RESULTS: Compared with the control group, the levels of FBG in the rats of the model group were obviously increased(P<0.01). In the OFT, the frequencies of rearing and grooming in the rats of model group markedly was decreased, while in the FST, the immobility time extensively was increased(P<0.01). The density of microglia in hippocampus CA1 region was increased(P<0.01). The expressions of P53, Iba1 and iNOS were increased, and the expressions of Arg-1 and BDNF were decreased(P<0.01). Additionally, compared with the model group, in the OFT, the frequencies of rearing and grooming were increased in the rats in 150 and 300 mg/kg TP group(P<0.01). The density of microglia in hippocampus CA1 region was decreased(P<0.01). The expressions of P53, Iba1 and iNOS were down-regulated, and the expression of BDNF was up-regulated(P<0.01). Additionally, compared with the model group, the levels of FBG was decreased in the rats in the 300 mg/kg TP group(P<0.01). The immobility time was decreased in the FST(P<0.01). The expression of Arg-1 was down-regulated(P<0.01).
CONCLUSIONS: TP can improve depression-like behavior in aged T2DM model rats, and its mechanism may be related to regulate microglia M1/M2 polarization and up-regulate expression of BDNF in hippocampus.
METHODS: A total of 40 8-week-old SD male rats were randomly divided into the control group(n=10) and the modeling group(n=30) according to the body weight. The rats in the modeling group were fed with high-glucose and high-fat diet and treated with 50 mg/kg D-galactose by intraperitoneal injection daily until the end of the experiment, while the rats in the control group were fed with the standard diet and treated with an equal volume of saline by intraperitoneal injection. After 4 weeks, the rats in the modeling group were injected with 25 mg/kg STZ, meanwhile the rats in the control group were injected with an equal volume of citric acid buffer. The level of fasting blood glucose(FBG) was measured on the 14~(th) day. When FBG≥16.7 mmol/L, the rats were identified as successful model of the T2DM rats. Then, the model rats were randomly divided into the model group, 150, 300 mg/kg TP groups(n=10, respectively), and the rats were given intragastric intervention for 8 weeks. The levels of the FBG were detected, and the depression-like behavior of rats was assessed by the open field test(OFT) and forced swimming test(FST). The density of microglia in hippocampus CA1 region was assessed by immunofluorescence staining, and protein expressions of P53, Iba1, iNOS, Arg-1 and BDNF were determined by western blot.
RESULTS: Compared with the control group, the levels of FBG in the rats of the model group were obviously increased(P<0.01). In the OFT, the frequencies of rearing and grooming in the rats of model group markedly was decreased, while in the FST, the immobility time extensively was increased(P<0.01). The density of microglia in hippocampus CA1 region was increased(P<0.01). The expressions of P53, Iba1 and iNOS were increased, and the expressions of Arg-1 and BDNF were decreased(P<0.01). Additionally, compared with the model group, in the OFT, the frequencies of rearing and grooming were increased in the rats in 150 and 300 mg/kg TP group(P<0.01). The density of microglia in hippocampus CA1 region was decreased(P<0.01). The expressions of P53, Iba1 and iNOS were down-regulated, and the expression of BDNF was up-regulated(P<0.01). Additionally, compared with the model group, the levels of FBG was decreased in the rats in the 300 mg/kg TP group(P<0.01). The immobility time was decreased in the FST(P<0.01). The expression of Arg-1 was down-regulated(P<0.01).
CONCLUSIONS: TP can improve depression-like behavior in aged T2DM model rats, and its mechanism may be related to regulate microglia M1/M2 polarization and up-regulate expression of BDNF in hippocampus.
摘要：
目的：观察茶多酚对老年2型糖尿病(T2DM)模型大鼠抑郁样行为的改善作用。
方法：将40只8周龄SD雄性大鼠按体重随机分为对照组(n=10)和造模组(n=30)。造模组大鼠饲喂高糖高脂饮食,每天腹腔注射50mg/kgD-半乳糖,直至实验结束,对照组用标准饮食喂养，腹腔注射等体积生理盐水。4周后,模型组大鼠注射25mg/kgSTZ,对照组大鼠注射等体积的柠檬酸缓冲液。于第14天测定空腹血糖(FBG)水平。当FBG≥16.7mmol/L时,这些大鼠被鉴定为成功的T2DM大鼠模型。然后，将模型大鼠随机分为模型组,150、300mg/kgTP组（分别为n=10），大鼠灌胃干预8周。检测到FBG的水平，通过旷场试验（OFT）和强迫游泳试验（FST）评估大鼠的抑郁样行为。通过免疫荧光染色评估海马CA1区小胶质细胞的密度，和P53，Iba1，iNOS的蛋白表达，通过蛋白质印迹测定Arg-1和BDNF。
结果：与对照组相比，模型组大鼠FBG水平明显升高(P<0.01)。在OFT，模型组大鼠饲养和梳理频率明显降低，而在FST,不动时间广泛增加（P＆lt;0.01）。海马CA1区小胶质细胞密度增加(P<0.01)。P53、Iba1和iNOS的表达增加,Arg-1和BDNF的表达降低(P<0.01)。此外,与模型组相比，在OFT，150和300mg/kgTP组大鼠饲养和修饰频率增加（P＆lt;0.01）。海马CA1区小胶质细胞密度降低(P<0.01)。P53、Iba1和iNOS表达下调,BDNF表达上调(P<0.01)。此外,与模型组相比，300mg/kgTP组大鼠的FBG水平降低（P＆lt;0.01）。FST中的不动时间减少（P＆lt;0.01）。Arg-1表达下调(P<0.01)。
结论：TP可改善老年T2DM模型大鼠抑郁样行为,其机制可能与调节小胶质细胞M1/M2极化和上调海马BDNF的表达有关。
方法：将40只8周龄SD雄性大鼠按体重随机分为对照组(n=10)和造模组(n=30)。造模组大鼠饲喂高糖高脂饮食,每天腹腔注射50mg/kgD-半乳糖,直至实验结束,对照组用标准饮食喂养，腹腔注射等体积生理盐水。4周后,模型组大鼠注射25mg/kgSTZ,对照组大鼠注射等体积的柠檬酸缓冲液。于第14天测定空腹血糖(FBG)水平。当FBG≥16.7mmol/L时,这些大鼠被鉴定为成功的T2DM大鼠模型。然后，将模型大鼠随机分为模型组,150、300mg/kgTP组（分别为n=10），大鼠灌胃干预8周。检测到FBG的水平，通过旷场试验（OFT）和强迫游泳试验（FST）评估大鼠的抑郁样行为。通过免疫荧光染色评估海马CA1区小胶质细胞的密度，和P53，Iba1，iNOS的蛋白表达，通过蛋白质印迹测定Arg-1和BDNF。
结果：与对照组相比，模型组大鼠FBG水平明显升高(P<0.01)。在OFT，模型组大鼠饲养和梳理频率明显降低，而在FST,不动时间广泛增加（P＆lt;0.01）。海马CA1区小胶质细胞密度增加(P<0.01)。P53、Iba1和iNOS的表达增加,Arg-1和BDNF的表达降低(P<0.01)。此外,与模型组相比，在OFT，150和300mg/kgTP组大鼠饲养和修饰频率增加（P＆lt;0.01）。海马CA1区小胶质细胞密度降低(P<0.01)。P53、Iba1和iNOS表达下调,BDNF表达上调(P<0.01)。此外,与模型组相比，300mg/kgTP组大鼠的FBG水平降低（P＆lt;0.01）。FST中的不动时间减少（P＆lt;0.01）。Arg-1表达下调(P<0.01)。
结论：TP可改善老年T2DM模型大鼠抑郁样行为,其机制可能与调节小胶质细胞M1/M2极化和上调海马BDNF的表达有关。
