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茶多酚通过调节小胶质细胞极化改善老年2型糖尿病大鼠的抑郁样行为

[Tea polyphenols improves depression-like behavior in aged type 2diabetes rats by regulating microglia polarization].

作者信息

Xie Haoran, Feng Wenjuan, Wang Xi, Chen Shuangzhi, Cheng Le, Lyu Chenhui, Kou Jie, Wang Lili, Li Xuemin, Zhao Haifeng

机构信息

Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Key Laboratory of Coal Environmental Pathogenicity and Prevention, Taiyuan 030001, China.

Shanxi Provincial Center for Disease Control and Prevention, Taiyuan 030012, China.

出版信息

Wei Sheng Yan Jiu. 2024 Jan;53(1):71-87. doi: 10.19813/j.cnki.weishengyanjiu.2024.01.011.

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).

CONCLUSION

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

探讨茶多酚(TP)对改善老年2型糖尿病(T2DM)模型大鼠抑郁样行为的影响。

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)。造模组大鼠给予高糖高脂饮食,并每日腹腔注射50 mg/kg D-半乳糖直至实验结束,而对照组大鼠给予标准饮食并腹腔注射等体积生理盐水。4周后,造模组大鼠注射25 mg/kg链脲佐菌素(STZ),同时对照组大鼠注射等体积柠檬酸缓冲液。于第14天测量空腹血糖(FBG)水平。当FBG≥16.7 mmol/L时,大鼠被认定为T2DM大鼠成功模型。然后,将模型大鼠随机分为模型组、150、300 mg/kg TP组(每组n = 10),并对大鼠进行8周的灌胃干预。检测FBG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区小胶质细胞密度,采用蛋白质印迹法检测P53、Iba1、诱导型一氧化氮合酶(iNOS)、精氨酸酶-1(Arg-1)和脑源性神经营养因子(BDNF)的蛋白表达。

结果

与对照组相比,模型组大鼠的FBG水平明显升高(P<0.01)。在OFT中,模型组大鼠的竖毛和理毛频率显著降低,而在FST中,不动时间显著增加(P<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,而Arg-1和BDNF的表达降低(P<0.01)。此外,与模型组相比,在OFT中,150和300 mg/kg TP组大鼠的竖毛和理毛频率增加(P<0.01)。海马CA1区小胶质细胞密度降低(P<0.01)。P53、Iba1和iNOS的表达下调,BDNF的表达上调(P<0.01)。此外,与模型组相比, 300 mg/kg TP组大鼠的FBG水平降低(P<0.01)。FST中的不动时间减少(P<0.01)。Arg-1的表达下调(P<0.01)。

结论

TP可改善老年T2DM模型大鼠的抑郁样行为,其机制可能与调节小胶质细胞M1/M2极化及上调海马BDNF表达有关。

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