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1.成都中医药大学,成都 610075;
2.陕西中医药大学,陕西 咸阳 712046
周莉萍,在读博士,从事中医药防治内分泌代谢疾病的临床与实验研究,E-mail:zlpcrystal@sina.com
王飞,博士,教授,从事中医药防治呼吸病与老年病的临床与实验研究,E-mail:wangfei666v@163.com
收稿日期:2019-02-19,
网络出版日期:2019-05-17,
纸质出版日期:2019-09-05
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周莉萍, 张效科, 李桂梅, 等. 葛根芩连汤加减对糖尿病大鼠海马炎症因子的影响[J]. 中国实验方剂学杂志, 2019,25(17):1-6.
Li-ping ZHOU, Xiao-ke ZHANG, Gui-mei LI, et al. Effect of Modified Gegen Qinlian Tang on Inflammatory Factors in Hippocampus for Diabetic Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 1-6.
周莉萍, 张效科, 李桂梅, 等. 葛根芩连汤加减对糖尿病大鼠海马炎症因子的影响[J]. 中国实验方剂学杂志, 2019,25(17):1-6. DOI: 10.13422/j.cnki.syfjx.20191738.
Li-ping ZHOU, Xiao-ke ZHANG, Gui-mei LI, et al. Effect of Modified Gegen Qinlian Tang on Inflammatory Factors in Hippocampus for Diabetic Rats[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(17): 1-6. DOI: 10.13422/j.cnki.syfjx.20191738.
目的:
2
探讨葛根芩连汤加减对2型糖尿病(T2DM)大鼠认知功能及海马组织白细胞介素-1
β
(IL-1
β
),肿瘤坏死因子-
α
(TNF-
α
)和核转录因子-
κ
B(NF-
κ
B)蛋白表达的影响。
方法:
2
将62只大鼠随机选取12只作为空白组,其余50只以高脂高糖饮食及小剂量链脲佐菌素(STZ)腹腔注射诱导2型糖尿病模型,随机分为模型组、沙格列汀组、葛根芩连汤加减组。空白组和模型组大鼠分别灌胃蒸馏水10 mL·kg
-1
·d
-1
,沙格列汀组灌胃沙格列汀0.005 g·kg
-1
·d
-1
,葛根芩连汤加减组灌胃葛根芩连汤加减0.435 g·kg
-1
·d
-1
;8周后,采用Morris水迷宫观察大鼠学习记忆能力;苏木素-伊红(HE)染色法观察海马组织病理变化;蛋白免疫印迹法(Western blot)检测海马组织细胞浆和细胞核内NF-
κ
B p65蛋白的表达;酶联免疫吸附测定(ELISA)检测大鼠海马组织IL-1
β
,TNF-
α
的水平。
结果:
2
与正常组比较,模型组大鼠第4天平均潜伏期显著延长(
P
<
0.01),逃逸平台进入次数、有效区域运动时间和运动距离均显著降低(
P
<
0.01),细胞核内NF-
κ
B p65的蛋白表达显著上升(
P
<
0.01),大鼠海马中IL-1
β
,TNF-
α
表达水平明显升高(
P
<
0.05);与模型组比较,葛根芩连汤加减能明显缩短T2DM大鼠逃避潜伏期,增加穿越平台次数、有效区游泳路程及游泳时间(
P
<
0.05,
P
<
0.01),显著改善海马组织IL-1
β
,TNF-
α
和细胞核内NF-
κ
B p65蛋白表达水平(
P
<
0.05,
P
<
0.01)。
结论:
2
葛根芩连汤加减可以显著改善高糖高脂饮食加小剂量STZ诱导的T2DM大鼠模型的学习记忆能力,其作用机制可能是通过抑制大鼠海马炎症反应来实现的。
Objective:
2
To investigate the effect of modified Gegen Qinlian Tang on learning and memory ability and interleukin-1
β
(IL-1
β
)
tumor necrosis factor-
α
(TNF-
α
)
nuclear factor-
κ
B(NF-
κ
B) protein expression in hippocampus of type 2 diabetic (T2DM) rats.
Method:
2
A total of 62 rats were randomly divided into normal group (
n
=12)
and the remaining 50 rats were established by feeding high sugar and high fat diet and injecting with low dosage of streptozocin(STZ) to T2DM. The successful modeling rats were selected and randomly divided into model group
Saxagliptin and modified Gegen Qinlian Tang group. The normal group and the model group received 10 mL·kg
-1
·d
-1
nomal saline by intragastric administration. 0.005 g·kg
-1
·d
-1
Saxagliptin crude drug and 0.435 g·kg
-1
·d
-1
modified Gegen Qinlian Tang crude drug were given in Saxagliptin group and modified Gegen Qinlian Tang group
and all the treatment lasted for 8 weeks. Learning and memory ability of rats was observed by using Morris water maze. Histopathological changes of hippocampus was observed by hematoxylin-eosin staining.Western blot was used to test the NF-
κ
B p65 in the cytoplasmic and nucleus in rat hippocampus. Enzyme-linked immunosorbent assay(ELISA) was used to test the levels of IL-1
β
and TNF-
α
.
Result:
2
Compared with normal group
the mean incubation period of model group was significantly prolonged on the 4
th
day(
P
<
0.01)
the number of escape platform entry
the movement time and distance of the effective area were significantly decreased (
P
<
0.01)
the protein expression of NF-
κ
B p65 in the nucleus was significantly increased (
P
<
0.01)
and the expression levels of IL-1
β
TNF-
α
in the hippocampus were significantly increased (
P
<
0.05). Compared with normal group
modified Gegen Qinlian Tang could increase the number of crossing platform(
P
<
0.05
P
<
0.01)
the platform of swimming distance and swimming time (
P
<
0.05
P
<
0.01). The expression levels of IL-1
β
TNF-
α
and NF-
κ
B p65 in hippocampus were significantly improved.
Conclusion:
2
Modified Gegen Qinlian Tang could obviously improve the learning and memory ability of the T2DM rat model which was induced by the high-sugar
high-lipid diet and low-dose STZ
and the mechanism may be achieved by suppressing the inflammation of the rat's hippocampus.
Sarah W , Gojka R , Anders G , et al . Global prevalence of diabetes: estimates for the year 2000 and projections for 2030 [J]. Diabetes Care , 2004 , 27 ( 5 ): 1047 - 1053 .
Gábor M S , Barbara K , Eva R , et al . Soluble semicarbazide-sensitive amine oxidase(SSAO)activity is related to oxidative stress and subchronic inflammation in streptozotocin-induced diabetic rats [J]. Neurochem Int , 2006 , 48 ( 8 ): 746 - 752 .
Ozer S , Ayfer T , Gülden Z O , et al . Protective effect of resveratrol against naphthalene-induced oxidative stress in mice [J]. Ecotoxicol Environ Saf , 2008 , 71 ( 1 ): 301 - 308 .
苏杰英 , 李宏亮 , 杨文英 . 糖尿病性认知功能障碍:一个不容忽视的问题 [J]. 中华内分泌代谢杂志 , 2008 , 24 ( 5 ): 476 - 479 .
袁有才 , 张效科 , 问莉娜 , 等 . 新葛根芩连汤对糖尿病脑病大鼠血脑屏障通透性及occludin/Claudins-5蛋白表达的影响 [J]. 时珍国医国药 , 2018 , 29 ( 9 ): 2108 - 2111 .
袁有才 , 张效科 , 高碧峰 , 等 . 新葛根芩连汤对糖尿病大鼠海马HIF-1α及VEGF的影响 [J]. 时珍国医国药 , 2018 , 29 ( 2 ): 269 - 271 .
袁有才 , 高碧峰 , 王飞 , 等 . 新葛根芩连汤对糖尿病大鼠海马PI3K/Akt/CREB mRNA表达的影响 [J]. 四川中医 , 2018 , 36 ( 10 ): 31 - 33 .
潘玉萍 , 李树德 , 邹英鹰 . NF-κB及其相关因子与糖尿病认知功能障碍关系的研究进展 [J]. 医学研究生学报 , 2016 , 29 ( 7 ): 754 - 758 .
毛小元 , 周宏灏 , 刘昭前 . 蛇床子素通过抑制PI3K/Akt信号通路减轻糖尿病脑病的炎症反应 [J]. 中国老年学杂志 , 2015 , 35 ( 17 ): 4743 - 4746 .
刘继平 , 程玥 , 关建建 , 等 . 七福饮对糖尿病脑病模型大鼠认知障碍及神经病理改变的影响 [J]. 中药药理与临床 , 2015 , 31 ( 5 ): 15 - 19 .
张玉领 , 孙长颢 . 2型糖尿病动物模型的研究进展 [J]. 实用糖尿病杂志 , 2011 , 7 ( 4 ): 7 - 9 .
林心君 , 王麒又 , 辛金钟 , 等 . 高成模率和高稳定性的糖尿病大鼠模型制备——高脂高糖膳食+STZ体重联合体表面积法构建糖尿病大鼠模型 [J]. 中国老年学杂志 , 2013 , 33 ( 9 ): 2051 - 2054 .
黄继汉 , 黄晓晖 , 陈志扬 , 等 . 药理试验中动物间和动物与人体间的等效剂量换算 [J]. 中国临床药理学与治疗学 , 2004 , 9 ( 9 ): 1069 - 1072 .
Riccardo E M , Mark W J S , Rebecca M R , et al . Association between raised inflammatory markers and cognitive decline in elderly people with type 2 diabetes: the Edinburgh type 2 diabetes study [J]. Diabetes , 2010 , 59 ( 3 ): 710 - 713 .
Hwang I K , Choi J H , Nam S M , et al . Activation of microglia and induction of pro-inflammatory cytokines in the hippocampus of type 2 diabetic rats [J]. Neurol Res , 2014 , 36 ( 9 ): 824 - 832 .
Acharya N K , QI X , Goldwaser E L , et al . Retinal pathology is associated with increased blood-retina barrier permeability in a diabetic and hypercholesterolaemic pig model: beneficial effects of the LpPLA2 inhibitor Darapladib [J]. Diabetes Vasc Dis Res , 2017 , 14 ( 3 ): 200 - 213 .
SONG G J , Jung M , Kim J , et al . A novel role for protein tyrosine phosphatase 1B as a positive regulator of neuroinflammation [J]. J Neuroinflammation , 2016 , 13 ( 1 ): 86 .
吴帆 , 刘圣徽 , 朱金华 , 等 . 乌梅丸对2型糖尿病模型大鼠NF-κB p65及GLP-1的影响 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 21 ): 144 - 148 .
CAI K , QI D , HOU X , et al . MCP-1 upregulates amylin expression in murine pancreatic β cells through ERK/JNK-AP1 and NF-κB related signaling pathways independent of CCR2 [J]. PLoS One , 2011 , 6 ( 5 ): e19559 .
冷锦红 , 于世家 . 糖尿病与NF-κB信号转导通路 [J]. 中华中医药学刊 , 2008 , 26 ( 6 ): 1248 - 1250 .
袁有才 , 问莉娜 , 曹旸 , 等 . 糖尿病认知功能障碍的中医病因病机研究进展 [J]. 光明中医 , 2016 , 31 ( 24 ): 3687 - 3690 .
王芬 , 何华亮 . 张发荣运用葛根芩连汤治疗糖尿病经验 [J]. 中医杂志 , 2005 , 46 ( 2 ): 103 .
赵林华 , 连凤梅 , 姬航宇 , 等 . 仝小林教授运用不同剂量葛根芩连汤治疗2型糖尿病验案 [J]. 中国实验方剂学杂志 , 2011 , 17 ( 4 ): 249 - 251 .
薛久开 . 新加葛根芩连汤治疗2型糖尿病认知障碍的临床疗效观察 [D]. 成都 : 成都中医药大学 , 2016 .
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