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葛花总黄酮对2型糖尿病大鼠认知功能障碍及海马中脑源性神经营养因子表达的影响
Effects of Pueraria Lobata Total Flavonoids on Cognitive Dysfunction and Brain-Derived Neurotrophic Factor Expression in Hippocampus of Type 2 Diabetes Mellitus Rats
- 中国医院用药评价与分析 2020年20卷第11期 页码：1333-1336
- 作者机构：
1. 北京朝阳急诊抢救中心药剂科
2. 中国人民解放军总医院第七医学中心药理科
- 作者简介：
- 基金信息：北京市科学技术委员会科研计划项目（No.Z171200002115003）
DOI：10.14009/j.issn.1672-2124.2020.11.013
中图分类号： R285.5纸质出版日期：2020，
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[1]徐琳,李建霞,赵维娟,许雪廷,李娜,周燕,洪福娣.葛花总黄酮对2型糖尿病大鼠认知功能障碍及海马中脑源性神经营养因子表达的影响[J].中国医院用药评价与分析,2020,20(11):1333-1336+1339.
XU Lin, LI Jianxia, ZHAO Weijuan, et al. Effects of Pueraria Lobata Total Flavonoids on Cognitive Dysfunction and Brain-Derived Neurotrophic Factor Expression in Hippocampus of Type 2 Diabetes Mellitus Rats[J]. 2020,20(11):1333-1336.
[1]徐琳,李建霞,赵维娟,许雪廷,李娜,周燕,洪福娣.葛花总黄酮对2型糖尿病大鼠认知功能障碍及海马中脑源性神经营养因子表达的影响[J].中国医院用药评价与分析,2020,20(11):1333-1336+1339. DOI： 10.14009/j.issn.1672-2124.2020.11.013.
XU Lin, LI Jianxia, ZHAO Weijuan, et al. Effects of Pueraria Lobata Total Flavonoids on Cognitive Dysfunction and Brain-Derived Neurotrophic Factor Expression in Hippocampus of Type 2 Diabetes Mellitus Rats[J]. 2020,20(11):1333-1336. DOI： 10.14009/j.issn.1672-2124.2020.11.013.
摘要
目的:探讨葛花总黄酮对2型糖尿病大鼠认知功能障碍及海马中脑源性神经营养因子（BDNF）表达的影响。方法:将Wistar大鼠100只随机分为对照组、模型组、吡拉西坦组（10 mg/kg）、葛花总黄酮低剂量组（20 mg/kg）及葛花总黄酮高剂量组（40 mg/kg）
每组20只。模型组、吡拉西坦组、葛花总黄酮低及高剂量组均建立2型糖尿病大鼠模型
并于造模成功后给予相应药物灌胃;对照组和模型组大鼠灌胃等体积0.9%氯化钠溶液;给药体积均为10 ml/kg
1日1次
持续给予140 d。给药结束后
通过Morris水迷宫试验评价大鼠认知功能;采用苏木精-伊红染色观察大鼠海马神经元病理结构变化;检测大鼠海马组织中BDNF mRNA和蛋白
白细胞介素4（IL-4）、白细胞介素8（IL-8）和肿瘤坏死因子α（TNF-α）蛋白水平。结果:（1）对照组大鼠海马区神经元细胞结构正常;模型组大鼠海马区神经元大量坏死
有明显炎症细胞浸润;吡拉西坦组、葛花总黄酮低及高剂量组大鼠海马神经元细胞坏死减少
且神经元细胞结构较为完整。（2）与对照组相比
模型组大鼠逃避潜伏期时间明显延长
IL-4、IL-8及TNF-α蛋白表达水平明显升高
经过原平台位置的次数明显减少
原平台象限停留时间明显缩短
BDNF mRNA和蛋白表达水平明显降低
上述差异均有统计学意义（P <0.05）。（3）与模型组相比
吡拉西坦组、葛花总黄酮低及高剂量组大鼠逃避潜伏期时间明显缩短
IL-4、IL-8及TNF-α蛋白表达水平明显降低
经过原平台位置的次数明显增多
原平台象限停留时间明显延长
BDNF mRNA和蛋白表达水平升高
差异均有统计学意义（P <0.05）;与葛花总黄酮低剂量组相比
葛花总黄酮高剂量组大鼠逃避潜伏期时间明显缩短
IL-4、IL-8及TNF-α蛋白表达水平明显降低
经过原平台位置的次数明显增多
原平台象限停留时间明显延长
BDNF mRNA和蛋白表达水平明显升高
差异均有统计学意义（P <0.05）。（4）与吡拉西坦组相比
葛花总黄酮低剂量组大鼠逃避潜伏期时间明显延长
IL-4、IL-8及TNF-α蛋白表达水平明显升高
经过原平台位置的次数明显减少
原平台象限停留时间明显缩短
BDNF mRNA和蛋白表达水平明显降低
差异均有统计学意义（P <0.05）;葛花总黄酮高剂量组大鼠逃避潜伏期时间、原平台象限停留时间
IL-4、IL-8及TNF-α蛋白表达水平
经过原平台位置的次数
BDNF mRNA和蛋白表达水平与吡拉西坦组相比
差异均无统计学意义（P> 0.05）。结论:葛花总黄酮对2型糖尿病大鼠认知功能障碍的疗效明显
其机制与葛花总黄酮促进BDNF mRNA和蛋白表达
降低IL-4、IL-8及TNF-α表达水平
减轻胰岛素抵抗以及炎症反应有关。
Abstract
OBJECTIVE: To investigate the effects of pueraria lobata total flavonoids on cognitive dysfunction and brain-derived neurotrophic factor（ BDNF） expression in hippocampus of type 2 diabetes mellitus（ T2 DM） rats.METHODS: Totally 100 Wistar rats were randomly divided into the control group
model group
piracetam group（ 10 mg/kg）
pueraria lobata total flavonoids low（ 20 mg/kg） and high（ 40 mg/kg） dose group
with 20 cases in each group. T2 DM rats were established in model group
piracetam group and each dose group of pueraria lobata total flavonoids. After successful modeling
rats were given corresponding drugs by gavage. The control group and the model group were given the same volume of normal saline by gavage
the volume of administration was 10 ml/kg
once a day
for 140 d. At the end of the experiment
the cognitive function of rats was evaluated by Morris water maze test;hematoxylin eosin（ HE） staining was used to observe the pathological changes of hippocampal neurons in rats; mRNA and protein levels of BDNF
interleukin-4（ IL-4）
interleukin-8（ IL-8） and tumor necrosis factor-α（ TNF-α） protein in hippocampus were detected. RESULTS:（ 1） The neuron cell structure in the hippocampus of the control group was normal; the neurons in the hippocampus of the model group were massively necrotic with obvious inflammatory cell infiltration; the necrosis of hippocampal neurons in the piracetam group and the low and high dose group of pueraria lobata total flavonoids decreased
and the neuronal cell structure was relatively complete.（ 2） The escape latency time in the model group were longer than that in the control group
the expression levels of IL-4
IL-8 and TNF-α protein in the model group were higher than those in the control group
while the times of passing through the original platform position
staying time in the original platform quadrant
BDNF mRNA and protein expression levels were lower than those in the control group
with statistically significant differences（ P < 0. 05）.（ 3） The escape latency time in the piracetam group and pueraria lobata total flavonoids low and high dose group were shorter than that in the model group
the expression levels of IL-4
IL-8 and TNF-α protein in the piracetam group and pueraria lobata total flavonoids low and high dose group were lower than those in the model group
while the times of passing through the original platform position
staying time in the original platform quadrant
BDNF mRNA and protein expression levels were higher than those in the model group
with statistically significant differences（ P < 0. 05）. The escape latency time in the pueraria lobata total flavonoids high dose group was shorter than that in the pueraria lobata total flavonoids low dose group
the expression levels of IL-4
IL-8 and TNF-α protein in the pueraria lobata total flavonoids high dose group were lower than those in the pueraria lobata total flavonoids low dose group
while the times of passing through the original platform
staying time in the original platform quadrant
BDNF mRNA and protein expression levels were higher than those in the pueraria lobata total flavonoids low dose group
with statistically significant differences（ P < 0. 05）.（ 4） The escape latency time in the pueraria lobata total flavonoids low dose group was longer than that in the piracetam group
the expression levels of IL-4
IL-8 and TNF-α protein in the pueraria lobata total flavonoids low dose group were higher than those in the piracetam group
while the times of passing through the original platform
staying time in the original platform quadrant
BDNF mRNA and protein expression levels were lower than those in the piracetam group
with statistically significant differences（ P < 0. 05）. The escape latency time
IL-4
IL-8
TNF-α protein expression levels
times of passing through the original platform
staying time in the original platform quadrant
BDNF mRNA and protein expression levels in the pueraria lobata total flavonoids high dose group were similar to those in the piracetam group（ P >0. 05）. CONCLUSIONS: The protective effects of pueraria lobata total flavonoids on cognitive dysfunction in T2 DM rats is related to the mechanism that the total pueraria lobata total flavonoids can promote the mRNA and protein levels of BDNF
reduce the expression levels of IL-4
IL-8 and TNF-α
and alleviate the insulin resistance and inflammation.
关键词
葛花总黄酮2型糖尿病大鼠认知功能障碍脑源性神经营养因子
Keywords
Pueraria lobata total flavonoidsType 2 diabetes mellitusRatsCognitive dysfunctionBrain-derived neurotrophic factor
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