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当归多糖对糖尿病KK-Ay小鼠心肌细胞凋亡的影响
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崔阳阳 ,杨丽霞 ,米登海 ,魏瑞贤(1.甘肃中医药大学中医临床学院,兰州 730099;2.甘肃省中医药研究院
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中心实验室,兰州 730050)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2023)10-1211-05
DOI 10.6039/j.issn.1001-0408.2023.10.11
摘 要 目的 探讨当归多糖对糖尿病KK-Ay小鼠心肌细胞凋亡的影响。方法 将KK-Ay小鼠随机分为模型组、二甲双胍组(200
mg/kg)和当归多糖高、中、低剂量组(400、200、100 mg/kg),C57BL/6J小鼠作为空白组,每组8只,各组小鼠每日灌胃相应药液或生
理盐水1次,连续4周。末次给药后,检测小鼠的空腹血糖、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、胰岛素(INS)水平,心
肌组织中B细胞淋巴瘤2(Bcl-2)、活化的胱天蛋白酶(cleaved-caspase-3)、凋亡信号调节激酶1(ASK1)、磷酸化氨基末端蛋白激酶
(p-JNK)、磷酸化需肌醇酶1α(p-IRE1α)蛋白表达以及心肌细胞凋亡情况。结果 与模型组比较,二甲双胍组和当归多糖中、高剂
量组小鼠空腹血糖、TC、LDL-C含量和心肌细胞凋亡率以及p-JNK、p-IRE1α、ASK1、cleaved-caspase-3蛋白表达水平均显著降低,
INS水平和Bcl-2蛋白表达水平均显著升高(P<0.05或P<0.01)。结论 当归多糖可改善糖尿病KK-Ay小鼠的血糖和血脂水平,
抑制心肌细胞凋亡,其机制可能与抑制IRE1/ASK1/JNK信号通路有关。
关键词 当归多糖;糖尿病心肌病;KK-Ay小鼠;细胞凋亡;IRE1/ASK1/JNK信号通路
Effects of Angelica sinensis polysaccharide on the apoptosis of cardiomyocytes in diabetic KK-Ay mice
CUI Yangyang ,YANG Lixia ,MI Denghai ,WEI Ruixian(1. Clinical College of Traditional Chinese Medicine,
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Gansu University of Traditional Chinese Medicine, Lanzhou 730099, China;2. Central Laboratory of Gansu
Provincial Institute of Traditional Chinese Medicine, Lanzhou 730050, China)
ABSTRACT OBJECTIVE To investigate the effects of Angelica sinensis polysaccharide on the apoptosis of cardiomyocytes in
diabetic KK-Ay mice. METHODS KK-Ay mice were randomly divided into model group, metformin group (200 mg/kg) and A.
sinensis polysaccharide high-dose, medium-dose and low-dose groups (400, 200 and 100 mg/kg); C57BL/6J mice were included
in blank group, with 8 mice in each group. Each group was given relevant medicine intragastrically or normal saline, once a day,
for consecutive 4 weeks. After the final administration, the levels of fasting glucose, total cholesterol (TC), low-density
lipoprotein cholesterol (LDL-C) and insulin (INS) were detected; the protein expressions of B-cell lymphoma 2 (Bcl-2), cleaved-
caspase-3, apoptosis signal-regulated kinase 1 (ASK1), phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated inositol-
requiring enzyme 1α (p-IRE1α) in myocardium, and apoptosis in cardiomyocytes were also detected. RESULTS Compared with
model group, the fasting glucose, TC and LDL-C content, apoptotic rate of cardiomyocyte, protein expressions of p-JNK and p-
IRE1α, ASK1, cleaved-caspase-3 were significantly lower in the metformin group and A. sinensis polysaccharide medium-dose,
high-dose groups; INS level and relative expression of Bcl-2 protein were significantly increased (P<0.05 or P<0.01).
CONCLUSIONS A. sinensis polysaccharide can improve the levels of blood glucose and blood lipid and inhibit cardiomyocyte
apoptosis in diabetic KK-Ay mice, and the mechanism may be related to the inhibition of IRE1/ASK1/JNK signaling pathway.
KEYWORDS Angelica sinensis polysaccharide; diabetic cardiomyopathy; KK-Ay mice; apoptosis; IRE1/ASK1/JNK signaling
pathway
随着人们生活水平的逐渐提高,糖尿病的患病率逐 因 [1―2] 。心血管并发症是糖尿病的主要死亡原因,约44%
年提升,截至 2030 年,糖尿病全球患病率将上升到 的1型糖尿病患者和52%的2型糖尿病患者都死于心血
10.2%(5.78 亿人),将成为造成人们死亡的第七大原 管 疾 病 [1―2] 。 糖 尿 病 心 肌 病(diabetic cardiomyopathy,
Δ 基金项目 甘肃省科技计划项目(No.20JR10RA432) DCM)是糖尿病导致的主要心血管并发症之一。细胞凋
*第一作者 硕士研究生。研究方向:中医药防治糖尿病。E- 亡作为DCM的重要病理特征,参与了DCM病变的整个
mail:995563704@qq.com
[3]
过程 。内质网应激(endoplasmic reticulum stress,ERS)
# 通信作者 主任医师,硕士生导师,博士。研究方向:中医药防治
糖尿病。E-mail:yanglixia-415@163.com 会 诱 发 需 肌 醇 酶 1α(inositol-requiring enzyme 1α,
中国药房 2023年第34卷第10期 China Pharmacy 2023 Vol. 34 No. 10 · 1211 ·