机构地区:[1]成都中医药大学,成都610075 [2]四川省中医药科学院,四川省中医药转化医学中心,四川省道地药材系统开发工程技术研究中心,国家中医药管理局中药质量生物评价重点研究室,成都610041 [3]四川省中医药管理局,成都610012
出 处:《中药药理与临床》2020年第1期115-120,共6页Pharmacology and Clinics of Chinese Materia Medica
基 金:国家自然科学项目(编号:NSFC81703820);"国家重大新药创制"科技重大专项项目(编号:2018ZX09201018-029);四川省科技厅重点研发项目(编号:2018SZ0056)。
摘 要:目的:观察变叶海棠提取物对链脲佐菌素(STZ)所致糖尿病小鼠的降血糖作用及可能的作用机制。方法:采用STZ诱导糖尿病小鼠动物模型,诱导成功后按血糖随机分为模型对照组、罗格列酮2. 67 mg/kg组、变叶海棠提取物1. 5、3、6 g/kg剂量组,每组10只,雌雄各半;另设10只KM种小鼠作为正常对照组。灌胃给药干预38 d。实验期间每周固定时间测定体重、空腹血糖(FBG)、检测胰岛素耐量(ITT)、葡萄糖耐量(OGTT),实验结束时摘除眼球取血,分离血清,检测血清中总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、糖化血清蛋白(GSP)、胰高血糖素样肽-1(GLP-1)、胰高血糖素(Glucagon)、胰岛素(FINS)含量;摘取胰腺组织,制作石蜡切片,HE染色及TUNEL检测。结果:与正常对照组比较,模型对照组小鼠体重降低、血糖明显升高,血清中TC、TG、LDL、GSP含量明显升高,GLP-1、胰岛素含量明显降低(P <0. 05或P <0. 01),胰腺组织出现胰岛细胞变性或坏死、腺泡萎缩坏死。与模型对照组比较,变叶海棠提取物1. 5、3、6 g/kg可使链脲佐菌素所致糖尿病小鼠血糖明显降低、1. 5、3 g/kg可使LDL-C含量明显降低(P <0. 05或P <0. 01);有降低TC、TG、GSP含量,提高GLP-1、INS含量,降低细胞凋亡率趋势。结论:变叶海棠提取物可有效降低链脲菌素所致糖尿病小鼠血糖水平,对糖代谢、脂质代谢有改善作用,其作用机制可能与改善胰岛细胞凋亡、调节胰岛素分泌及降低胰岛素抵抗有关。Objective: To observe the hypoglycemic effect of the extract from Malus toringoides( Rehd.) Hughes. on streptozotocin-induced diabe-tes in mice and its possible mechanism. Methods: Diabetic mice model was established by STZ. After modeling,mice were randomly divided into the control group,the model group,rosiglitazone group( 2. 67 mg/kg),BHYT groups( 1. 5、3、6 g/kg),10 mice in each group,equal numbers of male and female mice. Corresponding drugs were orally given for 38 days. During the experiment,the body weight,fasting blood glucose,Insulin tolerance( ITT) and glucose tolerance( OGTT) were measured at the fixed time. After last administration,blood was collected from the eyeball,then serum was separated to detect total cholesterol( TC),triglyceride( TG),low-density lipoprotein cholesterol( LDL-C),glycosylated serum protein( GSP),glucagon-like peptide-1( GLP-1),Glucagon and insulin( FINS). Pancreatic tissues were taken to make paraffin sections,then observed by HE staining and TUNEL. Compared with the control group,the body weight was decreased in the model group,the blood glucose was increased,the contents of TC,TG,LDL-C,GSP in serum were increased,the contents of GLP-1 and insulin were decreased( P < 0. 05 or P < 0. 01). In pancreatic tissues,islet cell degeneration or necrosis,acinar atrophy necrosis was observed. Compared with the model group,the blood glucose was significantly reduced in 1. 5,3,6 g/kg groups,LDL-C content was significantly decreased in 1. 5 g/kg and 3 g/kg BHYT groups( P < 0. 05 or P < 0. 01). The contents of TC,TG and GSP were reduced,the contents of GLP-1 and INS were increased,the rate of apoptosis was reduced. Conclusion: The extract from Malus toringoides( Rehd.) Hughes. can effectively reduce the blood glucose levels of STZ-induced diabetic mice and improve the glucose metabolism and lipid metabolism. Its mechanism may be related to improving islet cell apoptosis,regulating insulin secretion and reducing insulin resistance.
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