番石榴叶总黄酮对2型糖尿病模型小鼠肝糖异生ERRγ CREBH信号通路相关因子的影响-中国药房

番石榴叶总黄酮对2型糖尿病模型小鼠肝糖异生ERRγ CREBH信号通路相关因子的影响

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篇名：	番石榴叶总黄酮对2型糖尿病模型小鼠肝糖异生ERRγ CREBH信号通路相关因子的影响
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摘要：	目的：探讨番石榴叶总黄酮（GLTF）对2型糖尿病（T2DM）模型小鼠肝脏雌激素相关受体γ（ERRγ）/环磷酸腺苷应答元件结合蛋白H（CREBH）通路相关因子的影响，探讨其降血糖作用的具体机制。方法：取健康雄性ICR小鼠，采用高糖高脂饲料喂养联合多次腹腔注射小剂量链脲佐菌素的方法建立T2DM模型。将造模成功的小鼠按血糖值随机分为模型组、二甲双胍组（阳性对照，0.17 g/kg）、消渴降糖胶囊组（阳性对照，0.75 g/kg）和GLTF低、高剂量组（0.047、0.094 g/kg），每组12只；另选12只正常小鼠作为正常组。除正常组和模型组小鼠灌胃等体积水外，其余各组小鼠灌胃相应药物溶液10 mL/kg，qd，连续21 d。给药结束后，检测各组小鼠空腹血糖值、血清胰岛素水平，计算胰岛素敏感指数（ISI）；采用苏木素-伊红染色法观察小鼠肝脏和胰腺组织病理学变化；采用免疫印迹法检测小鼠肝组织中ERRγ、CREBH的蛋白表达水平；采用实时定量聚合酶链式反应法检测小鼠肝组织中过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC1α）、CREB调节转录辅激活因子2（TORC2）的mRNA表达水平。结果：与正常组比较，模型组小鼠空腹血糖和血清胰岛素水平均显著升高，ISI值显著降低（P＜0.01）；肝组织病变明显、可见大量空泡；胰腺组织中胰岛数目减少、体积变小，胰岛细胞呈轻度空泡病变；肝组织中ERRγ、CREBH的蛋白表达水平及PGC1α、TORC2的mRNA表达水平均显著升高（P＜0.01）。与模型组比较，GLTF各剂量组小鼠上述血糖、胰岛素指标及病理学变化均明显改善；肝组织中ERRγ、CREBH的蛋白表达水平及PGC1α、TORC2的mRNA表达水平均显著降低（P＜0.05或P＜0.01）。结论：GLTF对T2DM模型小鼠具有明显降糖及肝、胰腺组织保护作用；其降血糖作用的机制可能与抑制肝脏ERRγ/CREBH信号通路有关。
ABSTRACT：	OBJECTIVE： To investigate the effects of total flavonoids from Psidium guajava leaves （GLTF） on the related factors for estrogen-associated receptor γ（ERRγ）/cyclic adenosine monophosphate responsive element binding protein H（CREBH）pathway in liver of type 2 diabetes mellitus（T2DM）model mice， and to investigate the specific mechanism of its hypoglycemic effect. METHODS： Healthy male ICR mice were collected. T2DM models were established by high-sugar and high-fat diet feeding combined with repeated intraperitoneal injection of low dose streptozotocin. According to the blood glucose value， model mice were randomly divided into model group， metformin group（positive control， 0.17 g/kg），Xiaoke jiangtang capsule group（positive control， 0.75 g/kg），GLTF low-dose and high-dose groups（0.047， 0.094 g/kg）， with 12 mice in each group. Another 12 normal mice were included in normal group. Except that normal group and model group were given constant volume of water intragastrically， other groups were given relevant solution 10 mL/kg intragastrically， qd， for consecutive 21 d. After administration， fasting blood glucose and serum insulin levels of mice were measured and insulin sensitivity index （ISI） was calculated. Histopathological changes of liver and pancreas were observed by HE staining. The protein expressions of ERRγ and CREBH in liver tissues were detected by immunoblotting. The mRNA expression of peroxisome proliferator-activated receptor-γ coactivator-1α（PGC1α）and CREB protein co-activator 2（TORC2）in liver tissue of mice were measured by RT-PCR. RESULTS： Compared with normal group， the levels of fasting blood glucose and serum insulin in T2DM mice were significantly increased in model group， while ISI was decreased significantly （P＜0.01）. The pathological changes of liver tissue were obvious and a large number of vacuoles could be seen. The number and volume of islets in pancreatic tissue decreased， and islet cells showed mild vacuolar lesions. The protein expression of ERRγ and CREBH， mRNA expression of PGC1α and TORC2 in liver tissue were increased significantly （P＜0.01）. Compared with model group， above blood glucose， insulin indexes and pathological changes were improved significantly in GLTF groups. Protein expression of ERRγ and CREBH， mRNA expression of PGC1α and TORC2 in liver tissue were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： GLTF showed obvious hypoglycemic effect on T2DM model mice； its mechanism might be related to inhibiting ERRγ/CREBH signaling pathway.
期刊：	2019年第30卷第10期
作者：	王宏，傅予，王蕾，江茜，刘洪斌
AUTHORS：	WANG Hong，FU Yu，WANG Lei，JIANG Qian，LIU Hongbin
关键字：	2型糖尿病；番石榴叶总黄酮；雌激素相关受体γ；环磷酸腺苷应答元件结合蛋白H；过氧化物酶体增殖物激活受体γ辅激活因子1α；CREB调节转录辅激活因子2；小鼠
KEYWORDS：	Type 2 diabetes mellitus；Total flavonoids from Psidium guajava leaves；Estrogen-associated receptor γ；Cyclic adenosine monophosphate responsive element binding protein H；Peroxisome proliferator-activated receptor-γ coactivator-1α；CREB TORC 2; Mice
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