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黄连-麦冬药对对2型糖尿病大鼠的改善作用及机制研究
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| 篇名： | 黄连-麦冬药对对2型糖尿病大鼠的改善作用及机制研究 |
| TITLE： | Study on the ameliorative effects and mechanisms of Coptidis Rhizoma-Ophiopogonis Radix herb pair in rats with type 2 diabetes mellitus |
| 摘要： | 目的 探讨黄连-麦冬药对（HLMD）对2型糖尿病（T2DM）大鼠的改善作用及潜在机制。方法将雄性Wistar大鼠分为正常组（6只）和造模组（30只）。造模组大鼠以高糖高脂饲料喂养联合链脲佐菌素腹腔注射的方式构建T2DM模型，并将造模成功的大鼠分为模型组、二甲双胍组（200mg/kg）和HLMD低、中、高剂量组（100、200、400mg/kg），每组6只。各组大鼠灌胃相应药液或生理盐水，每天1次，连续6周。检测各组大鼠体重、空腹血糖（FBG）、口服葡萄糖耐量实验曲线下面积（AUC）和血脂指标[总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）]、炎症因子[白细胞介素6（IL-6）、IL-1β、肿瘤坏死因子α（TNF-α）、IL-10]水平，观察肝脏、胰腺组织的病理形态学以及肝脏组织的脂质沉积情况，分析正常组、模型组、HLMD高剂量组大鼠的肠道菌群变化情况；借助网络药理学和分子对接分析HLMD改善T2DM的潜在靶点并验证。结果与模型组比较，HLMD各剂量组大鼠体重普遍回升，FBG持续下降；胰岛形态紊乱、肝细胞排列紊乱、肝索坏死、脂质沉积等病理改变均有不同程度改善；AUC（低剂量组除外），TC、TG、LDL-C、IL-6（低剂量组除外）、IL-1β、TNF-α水平，Simpson和Shannon指数，厚壁菌门、变形菌门和梭菌属的相对丰度均显著降低；HDL-C（低剂量组除外）、IL-10（低剂量组除外）水平，拟杆菌门和联合乳杆菌属的相对丰度均显著升高（P＜0.05）。网络药理学和分子对接预测结果显示，HLMD活性成分（槲皮素、腺苷、齐墩果酸、豆甾醇、麦冬皂苷D′等）可通过靶向蛋白激酶B1（Akt1）、TNF、IL-6、P53、IL-1β等关键靶点来改善T2DM。验证结果显示，HLMD可显著下调T2DM大鼠肝组织中P53（低剂量组除外）、IL-6（低剂量组除外）、IL-1β、TNF-α蛋白的表达（P＜0.05）。结论HLMD可改善T2DM大鼠的糖脂代谢紊乱，减轻炎症反应及肝脏、胰腺组织的病理损伤；上述作用可能与该药对调节肠道菌群组成及下调P53、IL-6、IL-1β、TNF-α等炎症相关靶点的表达有关。 |
| ABSTRACT： | OBJECTIVE To investigate the ameliorative effects of Coptidis Rhizoma-Ophiopogonis Radix herb pair （HLMD） in rats with type 2 diabetes mellitus （T2DM） and its potential mechanisms.METHODS Male Wistar rats were randomly divided into a control group （6 rats） and a model induction group （30 rats）. The T2DM rat model was established by feeding a high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The successfully modeled rats were subsequently divided into the model group， the metformin group （200 mg/kg）， and the low-， medium-， and high-dose HLMD groups （100， 200 and 400 mg/kg， respectively）， with six rats in each group. Rats in each group were administered the corresponding drug solution or normal saline by oral gavage once daily for six consecutive weeks. Body weight， fasting blood glucose （FBG）， the area under the curve （AUC） of the oral glucose tolerance test， serum lipid profiles [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）]， and inflammatory cytokine [interleukin-6 （IL-6）， IL-1β， tumor necrosis factor-α （TNF-α）， and IL-10] levels were measured. Histopathological changes in liver and pancreatic tissues， as well as hepatic lipid accumulation， were evaluated. Changes in gut microbiota composition were analyzed in the control， model， and high-dose HLMD groups. Network pharmacology and molecular docking analyses were performed to identify potential therapeutic targets of HLMD against T2DM， followed by experimental validation.RESULTS Compared with the model group， the body weight generally recovered in rats in all HLMD dose groups， while FBG levels consistently decreased. Histopathological abnormalities， including disrupted pancreatic islet architecture， disorganized hepatocyte arrangement， hepatic cord necrosis， and lipid accumulation， were alleviated to varying degrees. AUC （except for the low-dose group）， levels of TC， TG， LDL-C， IL-6（except for the low-dose group）， IL-1β and TNF-α， Simpson and Shannon indices， as well as the relative abundances of Firmicutes， Proteobacteria， and Clostridium were significantly reduced； meanwhile， the levels of HDL-C（except for the low-dose group） and IL-10 （except for the low-dose group）， as well as the relative abundances of Bacteroidota and Ligilactobacillus were significantly increased （ P ＜0.05）. Network pharmacology and molecular docking analyses suggested that the active constituents of HLMD， including quercetin， adenosine， oleanolic acid， stigmasterol， and ophiopogonin D′， may exert antidiabetic effects by targeting key proteins such as protein kinase B1（Akt1）， TNF， IL-6， P53 and IL-1β. Experimental validation further demonstrated that HLMD significantly downregulated the protein expressions of P53 （except for the low-dose group）， IL-6 （except for the low-dose group）， IL-1β and TNF-α in the liver tissues of T2DM rats （ P ＜0.05）.CONCLUSIONS HLMD alleviates glucose and lipid metabolism disorders， attenuates inflammatory responses， and ameliorates hepatic and pancreatic tissue damage in T2DM rats. These beneficial effects may be associated with the modulation of gut microbiota composition and the downregulation of inflammation-related targets， including P53， IL-6， IL-1β and TNF-α. |
| 期刊： | 2026年第37卷第20期 |
| 作者： | 李秋芳；李少玉；龚曼；马荣增；王梦梦；张琼琼；高境鸿；代丽萍；许二平；刘雅琳 |
| AUTHORS： | LI Qiufang，LI Shaoyu，GONG Man， MA Rongzeng，WANG Mengmeng，ZHANG Qiongqiong，GAO Jinghong，DAI Liping，XU Erping，LIU Yalin |
| 关键字： | 黄连-麦冬药对;糖脂代谢;炎症反应;肠道菌群;网络药理学;分子对接;作用机制 |
| KEYWORDS： | Coptidis Rhizoma-Ophiopogonis Radix herb pair;Glucose and lipid metabolism;Inflammatory response;gut microbiota;Network pharmacology;Molecular docking;Mechanism of action |
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