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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                                     Δ


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        史纪芳 ,潘佳琪 ,陈 梦 ,马 敬 ,王华伟 (1.大理大学临床医学院,云南 大理 671000;2.昆明医科大学第
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        一附属医院产科,昆明 650032;3.昆明医科大学第一附属医院生殖遗传科,昆明 650032)
        中图分类号 R714.7;R285.5        文献标志码 A           文章编号     1001-0408(2020)06-0671-06
        DOI  10.6039/j.issn.1001-0408.2020.06.07

        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)<6.67 mmol/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、200 mg/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25 mg/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(10 mL/kg);每
        日1次,连续18 d。分别于孕第3、7、18天(G3 d、G7 d、G18 d )检测其FBG水平;于G18 d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Western blotting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(G3 d、G7 d、G18 d )、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、AMPK mRNA、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(G3 d、G7 d、G18 d )、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、AMPK mRNA、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。
        关键词 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

        Improvement Effects of Total Flavonoids from Morus alba on Glycolipid Metabolism,Inflammation and
        Oxidative Stress in Gestational Diabetes Mellitus Model Rats Based on PPARγ Pathway
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        SHI Jifang ,PAN Jiaqi ,CHEN Meng ,MA Jing ,WANG Huawei(1. Clinical College,Dali University,Yunnan
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        Dali 671000,China;2. Dept. of Obstetrics,the First Affiliated Hospital of Kunming Medical University,
        Kunming 650032,China;3. Dept. of Reproductive Genetics,the First Affiliated Hospital of Kunming Medical
        University,Kunming 650032,China)
        ABSTRACT    OBJECTIVE:To study the improvement 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(G3 d,G7 d 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 18 d. 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(G3 d,G7 d,G18 d ),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 PPAR γ protein and mRNA,AMPK mRNA and p-AMPK
           Δ 基金项目:国家自然科学基金资助项目(No.81460240)
                                                           protein were significantly decreased (P<0.01). Compared
           * 副教授,硕士。研究方向:妇产科。E-mail:fcksjf@126.com
           # 通信作者:副研究员。研究方向:医学遗传学。E-mail:wang-             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


        中国药房    2020年第31卷第6期                                               China Pharmacy 2020 Vol. 31 No. 6  ·671  ·
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