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  

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

作　　者：史纪芳 潘佳琪 陈梦 马敬[2] 王华伟[3] SHI Jifang;PAN Jiaqi;CHEN Meng;MA Jing;WANG Huawei(Clinical College,Dali University,Yunnan Dali 671000,China;Dept.of Obstetrics,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,China;Dept.of Reproductive Genetics,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,China)

机构地区：[1]大理大学临床医学院,云南大理671000 [2]昆明医科大学第一附属医院产科,昆明650032 [3]昆明医科大学第一附属医院生殖遗传科,昆明650032

出　　处：《中国药房》2020年第6期671-676,共6页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81460240)。

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(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(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、AMPK m RNA、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m RNA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�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(G3d,G7d and G18d);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 G18d. The protein and m RNA expressions of PPARγ and NF-κB,the expression of AMPK m RNA and p-AMPK protein were measured by Real-time-PCR and Western blotting. RESULTS:Compared with control group,the levels of FBG(G3d,G7d and G18d),TG,TC,LDL-C,TNF-α,IL-6,IL-8 and MDA,protein and m RNA 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 m RNA,AMPK mRNA and p-AMPK protein were significantly decreased(P<0.01). Compared with GDM group,the levels of FBG(G3d,G7d and G18d),TG,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 m RNA expression of NF-κ B in M. alba total flavonoids groups were significantly decreased;the levels of SOD,GSH and CAT,the expressions of PPARγ protein and m RNA,AMPK mRNA and p-AMPK protein were significantly increased(P<0.05 or P<0.

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 

分 类 号：R714.7[医药卫生—妇产科学] R285.5[医药卫生—临床医学]