| 摘要: |
| 目的:基于过氧化物酶体增殖物激活受体α(PPARα)/肉毒碱棕榈酰转移酶-1(CPT-1)信号通路探讨补阳还五汤改善2型糖尿病(T2DM)合并高脂血症脂质代谢紊乱的作用机制。方法:将40只雄性SD大鼠随机分为空白组、模型组、辛伐他汀组和补阳还五汤组，每组10只。除空白组外均采用高脂高糖饮食+链脲佐菌素法建立T2DM合并高脂血症大鼠模型，空白组、模型组用生理盐水灌胃，辛伐他汀组给予辛伐他汀2.1 mg·kg-1·d-1灌胃，补阳还五汤组给予补阳还五汤6.39 g·kg-1·d-1灌胃，给药8周后取材，期间监测大鼠血糖水平。采用HE染色观察大鼠肝脏组织病理变化，生化法检测血清脂质代谢指标总胆固醇、甘油三酯、低密度脂蛋白胆固醇及高密度脂蛋白胆固醇水平，酶联免疫吸附测定法检测血清视黄醇结合蛋白4(RBP4)水平，采用聚合酶链式反应及蛋白免疫印迹法检测肝脏组织PPARα及CPT-1 的mRNA和蛋白表达水平。结果:与空白组比较，模型组大鼠空腹血糖升高，肝细胞脂肪变性且有淋巴细胞浸润，血清脂质代谢指标异常，血清RBP4水平升高，肝脏组织中PPARα和CPT-1 mRNA和蛋白表达量下降，差异有统计学意义(P <0.05)。与模型组比较，补阳还五汤组第8周空腹血糖降低，补阳还五汤组与辛伐他汀组肝细胞脂肪变性显著减少，未见明显炎性细胞浸润，血清脂质代谢指标显著改善，肝脏组织中PPARα和CPT-1 mRNA和蛋白表达升高，补阳还五汤组的血清RBP4含量降低，差异有统计学意义(P <0.05)。结论:补阳还五汤可能通过激活脂质代谢信号通路PPARα/CTP-1，从而提高酶活性、加速脂肪酸转运及氧化分解、减少脂质沉积，进而起到治疗T2DM合并高脂血症的作用。 |
| 关键词: 补阳还五汤 2型糖尿病 高脂血症 脂质代谢 过氧化物酶体增殖物激活受体α 肉毒碱棕榈酰转移酶-1 |
| DOI：10.3969/j.issn.1007-6948.2025.05.027 |
| 投稿时间：2025-02-09 |
| 基金项目:黑龙江省中医药科研项目(ZHY2024-052、ZHY2024-237) |
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| Exploring the mechanism of Buyang Huanwu decoction in improving lipid metabolism in rats with type 2 diabetes mellitus complicated with hyperlipidemia based on PPARα/CPT-1 pathway |
| WANG Qing-xiao,LIU Ai-jun,ZHANG Mei-jun |
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| Abstract: |
| Objective To explore the mechanism of Buyang Huanwu decoction in improving lipid metabolism disorder in type 2 diabetes mellitus (T2DM) complicated with hyperlipidemia based on the peroxisome proliferator-activated receptor alpha(PPARα)/carnitine palmitoyltransferase-1 (CPT-1) signaling pathway. Methods Forty male SD rats were randomly divided into blank group, model group, simvastatin group and Buyang Huanwu decoction group, with 10 rats in each group. Except for the blank group, the other groups were established with a rat model of T2DM complicated with hyperlipidemia by a high-fat and high-sugar diet + streptozotocin (STZ) method. The blank group and model group were given normal saline by gavage, the simvastatin group was given simvastatin at 2.1 mg·kg-1·d-1 by gavage, and the Buyang Huanwu decoction group was given Buyang Huanwu decoction at 6.39 g·kg-1·d-1 by gavage. The rats were sacrificed after 8 weeks of treatment, the blood glucose levels of the rats were monitored during this period. HE staining was used to observe the pathological changes of liver tissue, and biochemical methods were used to detect the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in serum. The levels of serum retinol binding protein 4 (RBP4) were detected by enzyme-linked immunosorbent assay. The expressions of PPARα and CPT-1 mRNA and protein in liver tissue were detected by polymerase chain reaction and Western blotting. Results Compared with the blank group, the model group had elevated fasting blood glucose, fatty degeneration of liver cells and lymphocyte infiltration, abnormal lipid metabolism indicators in serum, elevated serum RBP4 levels, and decreased expressions of PPARα and CPT-1 mRNA and protein in liver tissue, with statistically significant differences (P <0.05). Compared with the model group, the Buyang Huanwu decoction group had decreased fasting blood glucose at the 8th week, significantly reduced fatty degeneration of liver cells, no obvious inflammatory cell infiltration, significantly improved lipid metabolism indicators in serum, increased expressions of PPARα and CPT-1 mRNA and protein in liver tissue, and decreased serum RBP4 content, with statistically significant differences (P <0.05). Conclusion Buyang Huanwu decoction may play a therapeutic role in T2DM combined with hyperlipidemia by activating the lipid metabolism signaling pathway PPARα/CPT-1, thereby increasing enzyme activity, accelerating the transport and oxidation of fatty acids, and reducing lipid deposition. |
| Key words: Buyang Huanwu decoction type 2 diabetes mellitus hyperlipidemia lipid metabolism peroxisome proliferator-activated receptor α carnitine palmitoyltransferase-1 |
