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  

Effect and mechanism of Qingxue xiaozhi jiangtang formula on insulin resistance in rats with type 2 diabetes mellitus

作　　者：洪雨欣 张蕾[1] 周明学[1] 李思耐[1] 蔺莉 张萌 郭子轩 刘卫红[1] HONG Yuxin;ZHANG Lei;ZHOU Mingxue;LI Sinai;LIN Li;ZHANG Meng;GUO Zixuan;LIU Weihong(Beijing Institute of Traditional Chinese Medicine,Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University,Beijing 100010,China;Dept.of Ulcerative Vascular Surgery,Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University,Beijing 100010,China)

机构地区：[1]首都医科大学附属北京中医医院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

出　　处：《中国药房》2025年第1期24-29,共6页China Pharmacy

基　　金：国家自然科学基金项目(No.82274284)。

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。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<0.05);the pathological damage of liver tissue had significantly improved,and the phosphorylation levels of PERK and FOXO1 proteins in liver tissue were significantly decreased(P<0.05).CONCLUS

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 

分 类 号：R285[医药卫生—中药学] R965[医药卫生—中医学]