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基于PPARγ途径探讨桑叶总黄酮对妊娠期糖尿病模型大鼠糖脂代谢、炎症和氧化应激的改善作用
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| 篇名： | 基于PPARγ途径探讨桑叶总黄酮对妊娠期糖尿病模型大鼠糖脂代谢、炎症和氧化应激的改善作用 |
| TITLE： | Improvement Effects of Total Flavonoids from Morus alba on Glycolipid Metabolism ，Inflammation and Oxida- tive Stress in Gestational Diabetes Mellitus Model Rats Based on PPARγ Pathway |
| 摘要： | 目的：研究桑叶总黄酮对妊娠期糖尿病（GDM）模型大鼠糖脂代谢、炎症和氧化应激的改善作用，并探讨其可能机制。方法：雌性SD大鼠连续喂养高脂饲料8周后，将空腹血糖（FBG）＜6.67mmol/L的雌鼠与雄性SD大鼠合笼；将妊娠大鼠随机分为对照组、GDM组以及桑叶总黄酮低、中、高剂量组（50、100、200mg/kg），每组10只。除对照组外，其余各组均单次腹腔注射链脲佐菌素25mg/kg以复制GDM模型。于注射后，各给药组大鼠均灌胃相应药物，对照组和GDM组大鼠均灌胃生理盐水（10mL/kg）；每日1次，连续18d。分别于孕第3、7、18天（G3d、G7d、G18d）检测其FBG水平；于G18d检测其血脂[三酰甘油（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）]和血清炎症细胞因子[肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-8、]、氧化应激指标[丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH）、过氧化氢酶（CAT）]水平，采用荧光定量聚合酶链反应法和Westernblotting法分别检测其胎盘组织中过氧化物酶增殖体激活受体γ（PPARγ）和核因子κB（NF-κB）蛋白及mRNA，AMP依赖的蛋白激酶（AMPK）mRNA以及磷酸化AMPK（p-AMPK）蛋白的表达情况。结果：与对照组比较，GDM组大鼠FBG（G3d、G7d、G18d）、TG、TC、LDL-C、TNF-α、IL-6、IL-8、MDA水平以及NF-κB蛋白及mRNA的表达量均显著升高，而SOD、GSH、CAT水平以及PPARγ蛋白及mRNA、AMPKmRNA、p-AMPK蛋白的表达量均显著降低（P＜0.01）。与GDM组比较，桑叶总黄酮中、高剂量组大鼠FBG（G3d、G7d、G18d）、TG、TC、LDL-C水平以及各剂量组TNF-α、IL-6、IL-8、MDA水平，NF-κB蛋白及mRNA的表达量均显著降低，而桑叶总黄酮各剂量组大鼠SOD、GSH、CAT水平以及PPARγ蛋白及mRNA、AMPKmRNA、p-AMPK蛋白的表达量均显著升高（P＜0.05或P＜0.01）。结论：桑叶总黄酮对GDM模型大鼠的糖脂代谢、炎症和氧化应激均具有一定的改善作用，其机制可能与PPARγ途径的激活有关。 |
| ABSTRACT： | OBJECTIVE：To study the improvem ent effects of total flavonoids from Morus alba on glycolipid metabolism ， inflammation and oxidative stress in gestational diabetes mellitus （GDM）model rats ，and to investigate the potential mechanism. METHODS：After feeding high fat diet for 8 weeks，female SD rats with FBG ＜6.67 mmol/L were caged with male SD rats . Pregnant female rats were randomly divided into control group ，GDM group ，M. alba total flavonoids low-dose ，medium-dose and high-dose groups （50，100，200 mg/kg），with 10 rats in each group. Except for control group ，other groups were given intraperitoneal injection of streptozotocin 25 mg/kg once to induce GDM model. After injection ，rats in each administration group were given corresponding drugs intragastrically ，control group and GDM group were given normal saline 10 mL/kg intragastrically ， once a day ，for consecutive 18 days. The levels of FBG were determined on the 3rd，7th and 18th day of pregnancy （G3d，G7d and G18 d）；the levels of blood lipids （TG，TC，LDL-C，HDL-C）and inflammatory factors （TNF-α，IL -6，IL-8），oxidative stress indicators（MDA，SOD，GSH，CAT）in serum were determined on G 18d. The protein and mRNA expressions of PPARγ and NF-κB， the expression of AMPK mRNA and p-AMPK protein were measured by Real-time-PCR and Western blotting. RESULTS ： Compared with control group ，the levels of FBG （G3d，G7d，G18d），TG，TC，LDL-C，TNF-α，IL-6，IL-8 and MDA ，protein and mRNA expression of NF-κB in GDM group were significantly increased，while the levels of SOD ，GSH and CAT ，the expressions of PPARγ protein and mRNA，AMPK mRNA and p-AMPK fcksjf@126.com protein were significantly decreased （P＜0.01）. Compared with GDM group ，the levels of FBG （G3 d，G7 d，G18 d），TG， huawei99@163.com TC，LDL-C in M. alba total flavonoids medium-dose and high- dose groups and the levels of TNF-α，IL-6，IL-8 and MDA ，protein and mRNA expression of NF-κB in M. alba total flavonoids groups were significantly decreased ；the levels of SOD ，GSH and CAT ，the expressions of PPARγ protein and mRNA， AMPK mRNA and p-AMPK protein were significantly increased （P＜0.05 or P＜0.01）. CONCLUSIONS ：Total flavonoids from M. alba can improve the glycolipid metablism ，inflammation and oxidative stress in GDM model rats ，the mechanism of which may be related to the activation of PPARγ pathway. |
| 期刊： | 2020年第31卷第06期 |
| 作者： | 史纪芳，潘佳琪，陈梦，马敬，王华伟 |
| AUTHORS： | SHI Jifang，PAN Jiaqi，CHEN Meng，MA Jing，WANG Huawei |
| 关键字： | 妊娠期糖尿病；桑叶总黄酮；过氧化物酶增殖体激活受体γ；糖脂代谢；炎症；氧化应激；大鼠 |
| KEYWORDS： | Gestational diabetes mellitus ；Total flavonoids from Morus alba ；PPARγ；Glycolipid metabolism ；Inflammation； |
| 阅读数： | 281 次 |
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