茯苓多糖调节2型糖尿病模型大鼠肝脏糖异生的机制研究 点击下载
| 论文标题： | 茯苓多糖调节2型糖尿病模型大鼠肝脏糖异生的机制研究 |
| 英文标题： | |
| 中文摘要： | 目的 探讨茯苓多糖通过磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/叉头框转录因子O1（FoxO1）通路调节2型糖尿病模型大鼠血糖的作用和机制。方法将SD大鼠随机分为空白对照组（不造模、不给药）、模型组（造模、不给药）、二甲双胍组（造模，200mg/kg）和茯苓多糖低、中、高剂量组（造模，100、200、400mg/kg），每组8只。除空白对照组外，其余各组采用高脂饲料联合链脲佐菌素构建2型糖尿病大鼠模型。于造模同时，各给药组大鼠灌胃相应剂量的药物，空白对照组和模型组大鼠灌胃等体积水，每日1次，连续灌胃42d。实验期间，每日观察大鼠日常状况和体质量变化。给药结束前1d采集大鼠空腹血糖，进行口服葡萄糖耐量试验并计算曲线下面积（AUC）；末次给药后，计算大鼠心脏、肝脏、肾脏脏器指数；检测糖化血红蛋白（HbA1c）、总胆固醇（TC）、三酰甘油（TG）、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）水平及肝糖原含量；采用苏木精-伊红染色观察大鼠肝脏和胰腺组织病理形态学变化并计算病理等级评分；采用Westernblot法检测大鼠肝脏磷酸化PI3K（p-PI3K）、磷酸化Akt（p-Akt）、磷酸化FoxO1（p-FoxO1）、磷酸烯醇丙酮酸羧化激酶（PEPCK）、葡萄糖-6-磷酸酶（G6Pase）蛋白表达水平。结果与空白对照组比较，模型组大鼠出现多饮、多食、多尿症状，体质量、SOD、GSH-Px水平和p-PI3K、p-AKT、p-FoxO1蛋白表达水平均显著降低（P＜0.05）；大鼠肝脏、肾脏脏器指数，灌胃葡萄糖溶液0、0.5、2h时的血糖水平、AUC，空腹血糖水平、HbA1c水平，血清中MDA、TC、TG、肝糖原含量，肝脏、胰腺病理等级评分，PEPCK、G6Pase蛋白表达水平均显著升高（P＜0.05）。与模型组比较，茯苓多糖各剂量组大鼠日常情况均有所改善，以上指标均有不同程度的逆转。结论茯苓多糖可以通过减弱氧化应激，上调PI3K/Akt/FoxO1通路，从而下调糖异生关键酶PEPCK和G6Pase的蛋白表达，抑制肝脏糖异生，进而有效降低2型糖尿病模型大鼠的血糖水平，调节糖脂代谢。 |
| 英文摘要： | OBJECTIVE To investigate the effect and mechanism of Poria cocos polysaccharides on the regulation of blood glucose in type 2 diabetes mellitus （T2DM）model rats by phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）/forked box transcription factor O 1（FoxO1）pathway. METHODS SD rats were randomly divided into blank control group （no modeling ，no administration），model group （modeling，no administration ），metformin group （modeling，200 mg/kg）and P. cocos polysaccharide low-dose，medium-dose and high-dose groups （modeling，100，200，400 mg/kg），8 in each group. Except for blank control group ， other groups were given high fat diet combined with streptozotocin to construct the model of T 2DM rats. At the same time ， administration groups were given relevant dose of medicine intragastrically ，and blank control group and model group were given constant volume of water intragastrically ，once a day ，for consecutive 42 days. During the experiment ，general condition and bodyweight of rats were observed every day ；fasting blood glucose （FBG）of rats were collected ，and oral glucose tolerance test were conducted and area under curve （AUC）was calculated the day before last administration. After last medication ，the heart ，liver， kidney organ index were calculated ；the levels of HbA 1c，TC，TG，MDA，SOD，GSH-Px and hepatic glycogen content were detected. HE staining was used to observe the pathological changes of liver and pancreatic tissue ，and the pathological grade score was calculated. Western blot assay was used to detect the protein expressions of p-PI 3K，p-Akt，p-FoxO1， PEPCK and G 6Pase in liver tissues. RESULTS Compared with blank control group ，the rats of model group suffered cc1965@163.com from polydipsia ，polyphagia and polyuria ；the body weight ， the levels of SOD and GSH-Px ，the protein expressions of p-PI 3K，p-Akt and p-FoxO 1 were significantly decreased （P＜0.05）；liver and kidney organ index ，blood glucose level at 0，0.5 and 2 hours after intragastric administration of glucose solution ，AUC， FBG，HbA1c，serum levels of MDA ，TC，TG and hepatic glycogen content ，liver and pancreatic pathological grade score ，the protein expressions of PEPCK and G 6Pase were all increased significantly （P＜0.05）. Compared with model group ，the general condition of rats in P. cocos polysaccharide groups were all improved ，and all of above indicators had been reversed to varying degrees. CONCLUSIONS P. cocos polysaccharide can downregulate protein expressions of PEPCK and G 6Pase which are key enzymes of gluconeogenesis ，inhibit hepatic gluconeogenesis ，effectively decrease blood glucose levels and regulate glucolipid metabolism in T 2DM model rats by weakening oxidative stress and upregulating PI 3K/Akt/FoxO1 pathway. |
| 期刊： | 2022年第33卷第13期 |
| 作者： | 韩思婕，潘翔，朱芊芊，张丹丹，张涵瑞，方敬贤，魏琼，刘丹，叶晓川 |
| 英文作者： | HAN Sijie，PAN Xiang， ZHU Qianqian，ZHANG Dandan，ZHANG Hanrui，FANG Jingxian，WEI Qiong，LIU Dan，YE Xiaochuan |
| 关键字： | 茯苓多糖；2型糖尿病；氧化应激；PI3K/Akt/FoxO1通路；糖异生 |
| KEYWORDS： | Poria cocos polysaccharides；type 2 diabetes mellitus ；oxidative stress ；PI3K/Akt/FoxO1 pathway；gluconeogenesis |
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