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·药学研究·
清血消脂降糖方对2型糖尿病大鼠胰岛素抵抗的影响及机制 Δ
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洪雨欣 ,张 蕾 ,周明学 ,李思耐 ,蔺 莉 ,张 萌 ,郭子轩 ,刘卫红 (1.首都医科大学附属北京中医医院
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北京市中医药研究所,北京 100010;2.首都医科大学附属北京中医医院疮疡科,北京 100010)
中图分类号 R285;R965 文献标志码 A 文章编号 1001-0408(2025)01-0024-06
DOI 10.6039/j.issn.1001-0408.2025.01.05
摘 要 目的 探讨清血消脂降糖方对2型糖尿病(T2DM)大鼠胰岛素抵抗(IR)的改善作用及潜在机制。方法 采用腹腔注射30
mg/kg链脲佐菌素联合高脂高糖饲料喂养的方法建立T2DM大鼠模型。实验设置正常对照组,模型组,清血消脂降糖方低、高剂
量组(6.525、13.05 g/kg,以生药量计)和二甲双胍组(阳性对照,0.18 g/kg),每组8只。给药组大鼠灌胃相应药物,正常对照组、模型
组大鼠灌胃等体积生理盐水,每日1次,持续6周。测定大鼠体重、空腹血糖(FBG)并进行口服葡萄糖耐量试验,检测大鼠血清中
空腹胰岛素(FINS)水平并计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI),检测大鼠血清中血脂四项、肝功能、氧化应激
指标及炎症因子水平,观察大鼠肝组织病理变化,检测大鼠肝组织中蛋白激酶R样内质网激酶(PERK)、叉头框蛋白O1(FOXO1)
蛋白磷酸化水平。结果 与模型组相比,清血消脂降糖方高剂量组和二甲双胍组大鼠体重、ISI、高密度脂蛋白胆固醇、超氧化物歧
化酶水平显著升高(P<0.05),FBG、糖负荷120 min时的血糖值、葡萄糖曲线下面积、FINS、HOMA-IR、低密度脂蛋白胆固醇、总胆
固醇、甘油三酯、丙氨酸转氨酶、天冬氨酸转氨酶、碱性磷酸酶、丙二醛、白细胞介素6、肿瘤坏死因子α、C反应蛋白水平均显著降
低(P<0.05),肝组织病理损伤明显改善,肝组织中PERK、FOXO1蛋白磷酸化水平显著降低(P<0.05)。结论 清血消脂降糖方可
调节糖脂代谢、炎症因子及氧化应激水平,缓解T2DM大鼠IR,其作用机制可能与抑制PERK/FOXO1信号通路有关。
关键词 清血消脂降糖方;2型糖尿病;胰岛素抵抗;蛋白激酶R样内质网激酶;叉头框蛋白O1
Effect and mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance in rats with type 2
diabetes mellitus
HONG Yuxin ,ZHANG Lei ,ZHOU Mingxue ,LI Sinai ,LIN Li ,ZHANG Meng ,GUO Zixuan ,LIU Weihong 1
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(1. Beijing Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine Affiliated
to Capital Medical University, Beijing 100010, China;2. Dept. of Ulcerative Vascular Surgery, Beijing Hospital
of Traditional Chinese Medicine Affiliated to Capital Medical University, Beijing 100010, China)
ABSTRACT OBJECTIVE To investigate the improvement effect and potential mechanism of Qingxue xiaozhi jiangtang formula
on insulin resistance (IR) in type 2 diabetes mellitus (T2DM) rats. METHODS T2DM rat model was established by intraperitoneal
injection of 30 mg/kg streptozotocin combined with high-fat and high-sugar diet. The rats were randomly divided into normal
control group, model group, Qingxue xiaozhi jiangtang formula low-dose and high-dose groups (6.525, 13.05 g/kg, calculated by
raw material) and metformin group (positive control, 0.18 g/kg), with 8 rats in each group. Administration groups were given
relevant medicine intragastrically; normal control group and model group were given constant volume of normal saline
intragastrically, once a day, for consecutive 6 weeks. Body mass and fasting blood glucose (FBG) were determined, and oral
glucose tolerance test was conducted. Serum fasting insulin (FINS) level was measured to calculate the insulin resistance index
(HOMA-IR) and insulin sensitivity index (ISI). Additionally, the level of serum lipids, liver function, oxidative stress indicators
and inflammatory factors were assessed. The phosphorylation levels of kinase R-like endoplasmic reticulum kinase (PERK) and
forkhead box O1 (FOXO1) protein in liver tissue of rats were determined. RESULTS Compared with model group, the body
weight, ISI, the levels of high-density lipoprotein cholesterol and superoxide dismutase were increased significantly in Qingxue
xiaozhi jiangtang formula high-dose group and metformin group (P<0.05); FBG, blood glucose level at 120 minutes of glucose
loading, area under the curve of glucose, FINS, HOMA-IR, low-density lipoprotein cholesterol, total cholesterol, triglyceride,
alanine transaminase, aspartate transaminase, alkaline phosphatase, malondialdehyde, interleukin-6, tumor necrosis factor-α, and
C-reactive protein levels were significantly reduced (P<
Δ 基金项目 国家自然科学基金项目(No.82274284) 0.05); the pathological damage of liver tissue had significantly
*第一作者 硕士研究生。研究方向:中医药防治心血管和代谢性
improved, and the phosphorylation levels of PERK and
疾病。E-mail:569798354@qq.com
# 通信作者 教授,博士生导师,博士。研究方向:中医药防治心血 FOXO1 proteins in liver tissue were significantly decreased
管和代谢性疾病。E-mail:liuweihong@bjzhongyi.com (P<0.05). CONCLUSIONS Qingxue xiaozhi jiangtang
· 24 · China Pharmacy 2025 Vol. 36 No. 1 中国药房 2025年第36卷第1期