糖止方对2型糖尿病大鼠糖脂代谢的改善作用及机制 点击下载
| 论文标题： | 糖止方对2型糖尿病大鼠糖脂代谢的改善作用及机制 |
| 英文标题： | |
| 中文摘要： | 目的 探讨糖止方（TZF）改善2型糖尿病（T2DM）大鼠糖脂代谢紊乱的作用及机制。方法30只SPF级SD大鼠采用高脂饲料喂养+链脲佐菌素腹腔注射的方式构建T2DM大鼠模型。造模成功后分为模型组、二甲双胍组（阳性对照，0.18g/kg）及TZF低、中、高剂量组（（5、10、20g/kg）），每组6只；另选择6只大鼠作为空白组。各组大鼠灌胃相应体积药液或生理盐水，连续给药6周，每日1次。检测空腹血糖（FBG）、口服葡萄糖耐量实验的血糖曲线下面积（OGTT-AUC）、腹腔注射胰岛素耐量实验的血糖曲线下面积（IPITT-AUC）和血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）及高密度脂蛋白胆固醇（HDL-C）水平；以苏木精-伊红（HE）染色和油红O染色观察肝脏病理形态及脂质沉积；通过蛋白质组学分析筛选肝脏差异表达蛋白，并通过Westernblot和免疫荧光染色法对信号通路关键蛋白进行验证。结果与空白组比较，模型组大鼠FBG、OGTT-AUC、IPITT-AUC、LDL-C、TG、TC均显著升高（P＜0.05），HDL-C显著降低（P＜0.05）；肝组织出现肝索排列紊乱、肝细胞点状坏死及明显的脂质沉积，非酒精性脂肪性肝病活动度评分和脂滴阳性面积均显著升高/增大（P＜0.05）。与模型组比较，TZF低、中、高剂量组及二甲双胍组上述指标均显著回调（P＜0.05），肝组织病理损伤及脂质沉积减轻。蛋白质组学结果显示，模型组与空白组的差异表达蛋白共442个，TZF高剂量组与模型组的差异表达蛋白共358个，且差异表达蛋白中包含多个与葡萄糖和脂代谢密切相关的蛋白的表达在TZF干预后呈现逆转趋势；京都基因和基因组数据库通路富集分析显示，差异表达蛋白显著富集于过氧化物酶体增殖物激活受体（PPAR）信号通路。验证实验结果表明，TZF可显著上调大鼠肝组织中PPARα、PPARγ、载脂蛋白A1（ApoA1）的表达（P＜0.05），下调硬脂酰辅酶A去饱和酶1（SCD1）、脂滴包被蛋白2（PLIN2）的表达（P＜0.05）。结论TZF可改善T2DM大鼠的糖脂代谢紊乱；其机制可能与激活PPAR信号通路，调控下游脂代谢相关蛋白SCD1、PLIN2、ApoA1的表达有关。 |
| 英文摘要： | OBJECTIVE To investigate the effect and mechanism of Tangzhi formula（TZF） on improving glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats.METHODS Thirty SPF-grade SD rats were used to establish a T2DM rat model through high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats were divided into the model group， metformin group （positive control， 0.18 g/kg）， and TZF low-， medium-， and high-dose groups （5， 10， and 20 g/kg）， with 6 rats in each group. An additional 6 rats were selected as the blank group. The rats in each group were orally administered the corresponding volume of drug solution or saline， and continuous dosing was performed for 6 weeks， once daily. Fasting blood glucose （FBG）， area under the curve of oral glucose tolerance test （OGTT-AUC）， area under the curve of intraperitoneal insulin tolerance test （IPITT-AUC）， serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured. Hematoxylin-eosin （HE） staining and oil red O staining were used to observe hepatic pathological morphology and lipid deposition. Differentially expressed proteins in liver tissues were screened by proteomics analysis， and key proteins in signaling pathways were verified by Western blot and immunofluorescence staining.RESULTS Compared with the blank group， the levels of FBG， OGTT-AUC， IPITT-AUC， LDL-C， TG， and TC in the model group were significantly increased （ P ＜0.05）， while HDL-C level was significantly decreased （ P ＜0.05）； the liver tissues showed disordered hepatic cords， punctate necrosis of hepatocytes， and significant lipid deposition， the NAFLD activity score and positive area of lipid droplets were significantly increased（ P ＜0.05）. Compared with the model group， the above indicators in TZF low-， medium-， and high-dose groups and metformin group were significantly reversed （ P ＜0.05）； hepatic pathological injury and lipid deposition were alleviated. Proteomics results showed that a total of 442 differentially expressed proteins were screened between the model group and the blank group， and 358 differentially expressed proteins were screened between the TZF high-dose group and the model group. Among these differentially expressed proteins， multiple proteins closely related to glucose and lipid metabolism showed a reversal trend after TZF intervention. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the peroxisome proliferator-activated receptor （PPAR） signaling pathway was significantly enriched. The validation experiment results showed that TZF could significantly up-regulate the expression of PPARα， PPARγ， and apolipoprotein A1 （ApoA1） in rat liver tissues （ P ＜0.05）， and down-regulate the expression of stearoyl-CoA desaturase 1 （SCD1） and perilipin 2 （PLIN2） （ P ＜0.05）.CONCLUSIONS TZF can improve glucose and lipid metabolism disorders in T2DM rats； its mechanism may be related to the activation of the PPAR signaling pathway and the regulation of downstream lipid metabolism-related proteins SCD1， PLIN2， and ApoA1. |
| 期刊： | 2026年第37卷第16期 |
| 作者： | 陈静；白敏；尚付斌；于润生；宿艳；王剑锋；朱向东 |
| 英文作者： | CHEN Jing，BAI Min，SHANG Fubin，YU Runsheng，SU Yan，WANG Jianfeng，ZHU Xiangdong |
| 关键字： | 糖止方；2型糖尿病；糖脂代谢紊乱；PPAR信号通路；肝脏脂质沉积 |
| KEYWORDS： | Tangzhi formula;Type 2 diabetes mellitus;glucose and lipid metabolism disorders;PPAR signaling pathway;hepatic lipid deposition |
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