Institutional Repository of Xishuangbanna Tropical Botanical Garden
| 麻欠精油抗糖尿病作用研究 | |
| Alternative Title | The antidiabetic effects of essential oil of Zanthoxylum myriacanthum var. pubescens Huang (Maqian) |
| Mahmoud Mohammed Dahab Ibrahim a | |
| Thesis Advisor | 张萍 |
| 2020 | |
| Degree Grantor | 中国科学院大学 |
| Place of Conferral | 中国科学院西双版纳热带植物园 |
| Degree Name | 理学博士 |
| Degree Discipline | 植物学 |
| Keyword | 麻欠，精油，糖尿病，胰岛素抵抗，氧化应激，糖尿病肾病，代谢紊乱 |
| Abstract | 传统中药是治疗糖尿病的一类很好的药物。本论文的目的是用不同的糖尿病小鼠模型来评价傣药麻欠的抗糖尿病作用。此外，本研究还旨在评估麻欠精油对糖尿病小鼠的肾脏的保护作用及机制。第一，我们研究了麻欠精油对链脲佐菌素诱导的小鼠糖尿病的治疗作用。糖尿病诱导方法是给ICR 小鼠在腹部以200 mg/kg 的剂量单次注射链脲佐菌素。七天后，以灌胃方式给小鼠不同剂量的麻欠精油。结果表明麻欠精油对小鼠糖尿病症状有很大改善，这种改善很大可能是通过恢复β细胞数量和减少氧化应激来增强胰岛素分泌和改善胰腺功能。后续的机制研究表明，麻欠精油能够减轻胰腺的炎症反应、增加Nrf2 和血红素加氧酶-1 的表达量、抑制NF-κB 信号通路和caspase-3 蛋白表达水平、减少细胞炎症因子的产生和胰腺氧化应激反应。第二，高脂饲料饲养C57B/L6 雄性小鼠（6-8 周）45 天后，灌胃麻欠精油（100mg/kg 和150 mg/kg）6 周。结果显示，麻欠精油显著减少了小鼠的体重增加和食物摄入量。值得注意的是，我们的研究结果显示，麻欠精油在150 mg/kg 的情况下防止脂肪组织和肝脏增重并且显著改善葡萄糖耐受能力。麻欠精油还降低了血浆中胰岛素水平，包括非酯化脂肪酸(NEFA)、甘油三酯、胆固醇、低密度脂蛋白(LDL-c)、高密度脂蛋白(HDL-c)在内的脂质水平以及丙氨酸氨基转移酶(ALT)和天冬氨酸转氨酶(AST)。同时，麻欠精油还使β细胞结构和肝细胞的形态畸形得到了恢复，并减小了脂肪细胞的体积。第三，db/db 小鼠（9-10 周）适应性饲养7 天后灌胃麻欠精油（100 mg/kg 和150mg/kg）8 周。结果显示，麻欠精油显著抑制体重增加。db/db 小鼠的代谢表型的改善与食物摄入量的变化有关。麻欠精油治疗显著降低血浆中甘油三酯、胆固醇、NEFA、LDL-c、HDL、ALT 和AST 的水平。麻欠精油治疗过的小鼠在胰腺H&E 染色中显示β细胞的正常形态与数目，肝细胞中的脂肪滴数目减少且体积减小，肝脏组织学结构有所改善。未治疗的db/ db 小鼠的脂肪细胞体积较大，而150 mg/k 和100 mg/kg 麻欠精油治疗的db/ db 小鼠脂肪细胞的体积较小。结果表明，麻欠精油具有调节脂肪细胞脂肪积累和改善2 型糖尿病相关症状的作用。第四，本部分研究结果显示，在STZ 诱导的糖尿病小鼠模型中，麻欠精油通过抑制TNXIP 和Nrf2 通路来改善小鼠糖尿病肾病。灌胃麻欠精油显著了降低尿液的尿素和肌酐水平。此外，麻欠精油还恢复了抗氧化应激指标，包括MDA，维生素C 和肾脏中的抗氧化酶。同时,麻欠精油显著降低了TNF-α和IL-1β水平。综上所述，麻欠精油对三种模型的糖尿病小鼠有很好的治疗作用，并且还显著了改善小鼠糖尿病肾病的症状。我们证明，麻欠精油不仅可以逆转高血糖、改善胰岛素抵抗、改善肥胖、减少氧化应激，还能抑制在糖尿病和糖尿病肾病中起重要作用的信号通路。因此，麻欠精油有潜力开发成辅助治疗糖尿病的功能性食品。 |
| Other Abstract | Traditional Chinese medicine has been proposed to be a good source of medication for treating diabetes. The aim of this thesis was to evaluate the anti-diabetic effects of a traditional plant in Dai medicine called Maqian (Zanthoxylum myriacanthum var. pubescens Huang) in different diabetic mice models. In addition, this study also aimed to assess the mechanisms involved in the reno-protective effects of Maqian in diabetic mice. Firstly, we investigated the anti-diabetic effect of Maqian essential oil (MQEO) using STZinduced diabetes model. The diabetes in ICR mice was induced by injection of a single dose of streptozotocin (200 mg/kg i.p.). Seven days later, MQEO was administered orally with different doses. The study demonstrated that MQEO improved the diabetic condition in ICR mice which was most likely mediated through enhanced insulin secretion and improved pancreas functions by restoring β-cell mass, increasing insulin-positive β-cells, and decreasing oxidative stress. This was further supported by mechanistic studies which showed attenuated inflammation in pancreas, increased nuclear translocation of Nrf2, increased heme oxygenase-1, suppressed NF-κB signaling pathway, downregulated level of caspase-3, reduced cytokines, and reduced pancreas oxidative stress. Secondly, male C57B/L mice (6-8 weeks) were fed a high-fat diet (HFD) for 45 days. Then, we administrated MQEO to mice (100 and 150 mg/kg) orally for 6 weeks. The body weight gain and food intake were significantly reduced by MQEO. Noticeably, our results also showed that MQEO at 150 mg/kg prevented the fat pad and liver weight gain. Glucose tolerance was improved in MQEO treated diabetic mice. MQEO also attenuated elevated plasma levels of insulin and lipids including non-esterified fatty acid (NEFA), triglyceride, cholesterol, low density lipoprotein (LDL-c), high density lipoprotein (HDL-c), as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). MQEO normalized the histology deformities in diabetic mice including β-cell structure and liver loops. MQEO reduced the size of adipocytes. Thirdly, db/db mice (9-10 weeks) was acclimatized for 7 days then treated for 8 weeks with MQEO 100 and 150 mg/kg orally. MQEO significantly suppressed body weight gain. The improved metabolic phenotype of db/db mice was related to changes in food intake. Treatment with MQEO significantly decreased plasma levels of triglyceride, cholesterol, NEFA, LDL-c, HDL, ALT, and AST. Treated mice showed characteristic features of normal β-cell and normal cellular population in H&E stain of pancreas. Mice treated with MQEO showed few fat droplets in hepatocytes and improvement in histological structure of the liver. Non-treated Db/db mice showed larger size of adipocytes compared to treated mice, while db/db treated mice with MQEO 150 mg/kg and 100 mg/kg showed smaller size of adipocytes. The results indicated that MQEO has the ability to regulate fat accumulation in adipocytes and ameliorate type 2 diabetes associated symptoms. Fourthly, this study provided evidence that MQEO ameliorated diabetic nephropathy by attenuating TNXIP and Nrf2 pathways in streptozotocin induced diabetes in mice. Oral administration of MQEO significantly decreased the urine urea and creatinine levels. Furthermore, MQEO also normalized several oxidative stress parameters including malondaldehyde, vitamin C, and enzymatic antioxidants in kidney. In addition, TNF-α and IL-1β cytokines levels were also significantly reduced by MQEO. In summary, MQEO was effective in preventing and ameliorating diabetes and diabetic nephropathy complication in various models. We demonstrated that MQEO not only reversed hyperglycemia, improved insulin resistance, ameliorated obesity, and decreased oxidative stress but also attenuated some signaling pathways where are important in diabetes and diabetic nephropathy. Therefore, Maqian essential oil may be potentially developed into an adjunct therapy for treating diabetes as a functional food. Keywords: Zanthoxylum myriacanthum var. pubescens, essential oil, diabetes mellitus, insulin resistance, oxidative stress, diabetic nephropathy, metabolic disorders |
| Pages | 150 |
| Language | 中文 |
| Document Type | 学位论文 |
| Identifier | https://ir.xtbg.ac.cn/handle/353005/11710 |
| Collection | 西双版纳热带植物园毕业生学位论文 |
| Recommended Citation GB/T 7714 | Mahmoud Mohammed Dahab Ibrahim a. 麻欠精油抗糖尿病作用研究[D]. 中国科学院西双版纳热带植物园. 中国科学院大学,2020. |
| Files in This Item: | ||||||
| File Name/Size | DocType | Version | Access | License | ||
| MAHMOUD MOHAMMED DAH（9881KB） | 学位论文 | 开放获取 | CC BY-NC-SA | Application Full Text | ||
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment