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
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篇名: 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
TITLE: Effect and mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance in rats with type 2 diabetes mellitus
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30mg/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、13.05g/kg,以生药量计)和二甲双胍组(阳性对照,0.18g/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120min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。
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< Δ0.05); the pathological damage of liver tissue had significantlyimproved, and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased (P<0.05). CONCLUSIONS Qingxue xiaozhi jiangtang formula can regulate glucose and lipid metabolism, inflammation factor and oxidative stress levels, and alleviate insulin resistance in T2DM rats. Its mechanism of action may be related to the inhibition of the PERK/FOXO1 signaling pathway.
期刊: 2025年第36卷第01期
作者: 洪雨欣;张蕾;周明学;李思耐;蔺莉;张萌;郭子轩;刘卫红
AUTHORS: HONG Yuxin,ZHANG Lei,ZHOU Mingxue,LI Sinai,LIN Li,ZHANG Meng,GUO Zixuan,LIU Weihong
关键字: 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
KEYWORDS: Qingxue xiaozhi jiangtang formula; type 2 diabetes mellitus; insulin resistance; protein kinase R-like endoplasmic
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