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北华大学 药学院,吉林 吉林 132013
郭笑,博士,讲师,从事分子生物学研究,E-mail:395798544@qq.com
盛瑜,博士,讲师,从事药物分析研究,Tel:0432-64608008,E-mail:383165810@qq.com
纸质出版日期:2020-07-20,
网络出版日期:2020-04-15,
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郭笑,叶玉洁,宋昆等.五味子木脂素改善衰老小鼠学习记忆能力的机制[J].中国实验方剂学杂志,2020,26(14):85-91.
GUO Xiao,YE Yu-jie,SONG Kun,et al.Mechanism of Schisandrae Chinensis Fructus Lignans in Alleviating Learning and Memory Ability in D-galactose Aging Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):85-91.
郭笑,叶玉洁,宋昆等.五味子木脂素改善衰老小鼠学习记忆能力的机制[J].中国实验方剂学杂志,2020,26(14):85-91. DOI: 10.13422/j.cnki.syfjx.20201226.
GUO Xiao,YE Yu-jie,SONG Kun,et al.Mechanism of Schisandrae Chinensis Fructus Lignans in Alleviating Learning and Memory Ability in D-galactose Aging Mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(14):85-91. DOI: 10.13422/j.cnki.syfjx.20201226.
目的
2
研究五味子木脂素(Schisandrae Chinensis Fructus lignans,SCL)对
D
-半乳糖(
D
-galactose,
D
-gal)所致衰老模型小鼠学习记忆能力的改善作用。
方法
2
ICR小鼠随机分为4组,即正常组(灌胃蒸馏水,皮下注射生理盐水),模型组(灌胃蒸馏水,皮下注射200 mg·kg
-1
·d
-1
D
-gal),吡拉西坦组(灌胃吡拉西坦200 mg·kg
-1
·d
-1
,皮下注射
D
-gal 200 mg·kg
-1
·d
-1
),SCL低剂量组(灌胃SCL 50 mg·kg
-1
·d
-1
,皮下注射
D
-gal 200 mg·kg
-1
·d
-1
),SCL中剂量组(灌胃SCL 100 mg·kg
-1
·d
-1
,皮下注射
D
-gal 200 mg·kg
-1
·d
-1
),SCL高剂量组(灌胃SCL 200 mg·kg
-1
·d
-1
,皮下注射
D
-gal 200 mg·kg
-1
·d
-1
),连续给药10周;通过避暗实验及Morris水迷宫实验观察SCL对
D
-gal致衰老模型小鼠学习记忆能力的影响;通过化学比色法检测小鼠脑组织中超氧化物歧化酶(superoxide dismutase,SOD)活力及丙二醛(malondialdehyde,MDA)含量;通过聚合酶链式反应(polymerase chain reaction,PCR)检测小鼠脑组织中过氧化物还原酶-6(peroxiredoxin-6,Prdx6),谷胱甘肽过氧化酶1(glutathione peroxidase 1,GSH-Px1)mRNA表达情况;蛋白免疫印迹法(Western blot)检测小鼠组织中Prdx6,GSH-Px1蛋白表达情况。
结果
2
行为学实验中,与正常组比较,模型组小鼠避暗错误次数明显增加(
P
<
0.05),潜伏期显著减少(
P
<
0.01),小鼠穿台次数和目标象限停留时间显著减少(
P
<
0.01),可作为建模成功的指标。与模型组比较,吡拉西坦组,SCL中、高剂量组小鼠避暗错误次数明显减少(
P
<
0.05,
P
<
0.01),潜伏期明显延长(
P
<
0.05,
P
<
0.01),同时,SCL高剂量组小鼠水迷宫穿台次数和目标象限停留时间显著增加(
P
<
0.01)。与正常组比较,模型组小鼠脑组织中的SOD活力显著降低(
P
<
0.01),MDA含量增加(
P
<
0.05),Prdx6,GSH-Px1 mRNA及蛋白表达量明显下降(
P
<
0.05,
P
<
0.01)。与模型组比较,吡拉西坦组,SCL低、中、高剂量组小鼠脑组织中SOD活力增高(
P
<
0.05),MDA水平降低(
P
<
0.05),Prdx6,GSH-Px1 mRNA及蛋白的表达水平显著升高(
P
<
0.05,
P
<
0.01),说明SCL给药组具有剂量依赖性。
结论
2
SCL能改善
D
-gal致衰老模型小鼠学习记忆能力,该作用可能与SCL提高小鼠抗氧化能力及上调小鼠脑组织中Prdx6,GSH-Px1的表达水平有关。
Objective
2
To study the effect of Schisandrae Chinensis Fructus lignans (SCL) on learning and memory ability of
D
-galactose(
D
-gal)-induced aging model mice.
Method
2
ICR mice were randomly divided into 4 groups: normal group (distilled water
subcutaneous injection with normal saline)
model group (distilled water
subcutaneous injection with 200 mg·kg
-1
D
-gal)
piracetam group (oral administration with 200 mg·kg
-1
piracetam
subcutaneous injection with 200 mg·kg
-1
D
-gal)
low-dose SCL group (oral administration with 50 mg·kg
-1
·d
-1
SCL
subcutaneous injection with 200 mg·kg
-1
·d
-1
D
-gal)
medium-dose SCL group (oral administration with 100 mg·kg
-1
·d
-1
SCL
subcutaneous injection with 200 mg·kg
-1
·d
-1
D
-gal)
high-dose SCL group (oral administration with 200 mg·kg
-1
·d
-1
SCL
subcutaneous injection with 200 mg·kg
-1
·d
-1
D
-gal). The drugs were administered continuously for 10 weeks. Dark test and Morris water maze test were performed to observe the effect of SCL on the learning and memory ability of
D
-gal-induced aging mice. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in mouse brain tissue were detected by chemical colorimetry. The expressions of peroxiredoxin-6(Prdx6) and glutathione peroxidase 1(GSH-Px1) mRNA in mouse brain tissue were detected by polymerase chain reaction (PCR). The expressions of Prdx6 and GSH-Px1 protein in mouse tissues were detected by Western blot.
Result
2
In behavioral experiments
compared with normal group
the number of dark avoidance errors in model group significantly increased (
P
<
0.05)
the latency was significantly reduced (
P
<
0.01)
and the number of mouse passes and the target quadrant residence time were significantly reduced (
P
<
0.01)
which can be used as an indicator of successful modeling. Compared with the model group
the number of errors in the piracetam group
and medium and high-dose SCL groups was significantly reduced (
P
<
0.05,
P
<
0.01)
and the latency was significantly prolonged (
P
<
0.05,
P
<
0.01). At the same time
the number of water maze passes and the target quadrant retention time in the high-dose SCL group increased significantly (
P<
0.01). The results of biochemical indicators showed that compared with normal group
the SOD activity in brain tissue of model group mice was significantly reduced (
P
<
0.01)
while the MDA content was increased (
P
<
0.05). Compared with the model group
SOD activity in the brain tissues of piracetam group
and low
medium and high-dose piracetam groups was significantly increased (
P
<
0.05)
whereas the level of MDA was reduced (
P<
0.05). The expressions of Prdx6 and GSH-Px1 were significantly increased (
P
<
0.05,
P
<
0.01)
indicating that the SCL administration group was dose-dependent.
Conclusion
2
SCL can improve the learning and memory ability of
D
-gal-induced aging mice
which may be related to the anti-oxidation ability of SCL and the up-regulation of Prdx6 and GSH-Px1 expressions in mouse brain tissue.
五味子木脂素学习记忆能力谷胱甘肽过氧化酶1过氧化物还原酶-6
Schisandrae Chinensis Fructus lignanslearning and memory abilityglutathione peroxidase 1(GSH-Px1)peroxiredoxin-6(Prdx6)
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