肉桂多酚对链脲佐菌素致糖尿病小鼠的保护作用
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摘要
目的探讨肉桂多酚对链脲佐菌素(streptozotocin,STZ)致糖尿病小鼠的保护作用及其分子机制。方法建立单剂量STZ 240mg/kg诱导糖尿病小鼠模型,随机分成5组:STZ模型对照组、二甲双胍阳性组(0.3g/kg)及肉桂多酚低、中、高剂量组(0.3、0.6、1.2g/kg),持续每天灌胃,共14d。并设置正常对照组。末次给药后,血糖试纸测定空腹血糖(fasting blood-glucose,FBG),生化法测定血清胰淀粉酶含量,酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)测定血清胰岛素和胰高血糖素浓度,免疫组化法检测胰岛细胞中胰岛素阳性细胞数量,蛋白免疫印迹(Western blot)法检测胰脏细胞中蛋白激酶B(AKT)及其磷酸化水平。结果与STZ模型对照组小鼠比较,肉桂多酚干预组小鼠的血糖明显降低(P<0.05),血清胰岛素增加而胰高血糖素降低(P<0.05),胰岛细胞中胰岛素阳性细胞显著增加(P<0.05),胰脏细胞中蛋白激酶B(AKT)及其磷酸化水平同时增加(P<0.05),且表现为一定的剂量依赖性。结论肉桂多酚对STZ所致糖尿病小鼠胰脏损害表现出有效的细胞保护作用,其分子机制可能通过调节胰岛细胞AKT信号通路促进胰岛β细胞分泌胰岛,从而发挥降血糖药理活性。
Objective To investigate the protective effects of cinnamon polyphenols on streptozotocin-induced diabetic mice and its molecular mechanism.Methods A single dose of streptozotocin(streptozotocin,STZ;240mg/kg)was used to induce diabetic mouse model.The rats were randomly divided into five groups:STZ model control group,metformin(0.3g/kg),and low-,medium-and high-dose groups(0.3,0.6g/kg,and 1.2g/kg)every day continuously until day 14.The vehicle control was set up.After the last administration,the fasting blood glucose(FBG)value was measured by blood glucose test.Serum amylase content was measured by biochemical method.The serum insulin and glucagon concentration were measured by enzyme-linked immunosorbent assay(ELISA).The number of insulin-positive cells in islet cells was analyzed and the expression of protein kinase B(AKT)and its phosphorylation level in pancreatic cells were detected by Western blotting.Results Compared with diabetic mice,in the cinnamon polyphenols intervention groups the diabetic mice had significantly lower blood glucose(P <0.05),increased serum insulin,and decreased glucagon levels(P<0.05).The number of insulin-positive cells was significantly increased(P<0.05).The expression of protein kinase B(AKT)and its phosphorylation level in pancreatic cells increased in a dose-dependent manner.Conclusion Cinnamon polyphenols show effective cytoprotective effects on streptozotocininduced diabetic rats'pancreatic lesions,and their molecular mechanisms may be related to the promotion of isletβcell secretion by regulating pharmacological activities of the islet cell AKT signaling pathway.
Objective To investigate the protective effects of cinnamon polyphenols on streptozotocin-induced diabetic mice and its molecular mechanism.Methods A single dose of streptozotocin(streptozotocin,STZ;240mg/kg)was used to induce diabetic mouse model.The rats were randomly divided into five groups:STZ model control group,metformin(0.3g/kg),and low-,medium-and high-dose groups(0.3,0.6g/kg,and 1.2g/kg)every day continuously until day 14.The vehicle control was set up.After the last administration,the fasting blood glucose(FBG)value was measured by blood glucose test.Serum amylase content was measured by biochemical method.The serum insulin and glucagon concentration were measured by enzyme-linked immunosorbent assay(ELISA).The number of insulin-positive cells in islet cells was analyzed and the expression of protein kinase B(AKT)and its phosphorylation level in pancreatic cells were detected by Western blotting.Results Compared with diabetic mice,in the cinnamon polyphenols intervention groups the diabetic mice had significantly lower blood glucose(P <0.05),increased serum insulin,and decreased glucagon levels(P<0.05).The number of insulin-positive cells was significantly increased(P<0.05).The expression of protein kinase B(AKT)and its phosphorylation level in pancreatic cells increased in a dose-dependent manner.Conclusion Cinnamon polyphenols show effective cytoprotective effects on streptozotocininduced diabetic rats'pancreatic lesions,and their molecular mechanisms may be related to the promotion of isletβcell secretion by regulating pharmacological activities of the islet cell AKT signaling pathway.
引文
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[11]TOKUHIRA N,KITAGISHI Y,SUZUKI M,et al.PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy(Review)[J].Int J Mol Med,2015,35(1):10-16.
[2]徐海燕.中医中药疗效因素探析[J].中国当代医药,2011,18(36):92-93
[3]赵凯,姜勇,薛培凤,等.国产肉桂的化学成分研究[J].中草药,2013,44(17):2358-2363.
[4]梁晓艳,郭占京,罗佩卓,等.肉桂的药理作用研究概况[J].现代医药卫生,2013,(10):1501-1503.
[5]LI R,LIANG T,XU LY,et al.Protective effect of cinnamon polyphenols against STZ-diabetic mice fed high-sugar,high-fat diet and its underlying mechanism[J].Food Chem Toxicol,2013,51:419-425.
[6]潘澎,刘绍能.PI3K/Akt信号通路与肝纤维化[J].临床肝胆病杂志,2013,(5):389-392.
[7]DAYAL D,HEGDE A.Prevalence of islet autoantibodies in type 1diabetes[J].Indian J Endocrinol Metab,2017,21(3):485-486.
[8]MCDONALD TJ,COLCLOUGH K,BROWN R,et al.Islet autoantibodies can discriminate maturity-onset diabetes of the young(MODY)from type 1diabetes[J].Diabet Med,2011,28(9):1028-1033.
[9]DIAZ-VALENCIA PA,BOUGNERES P,VALLERON AJ.Global epidemiology of type 1diabetes in young adults and adults:A systematic review[J].BMC Public Health,2015,15:255.
[10]苏杰英,杨文英.胰岛素强化治疗过程中的低血糖:持续皮下胰岛素输注与每日多次胰岛素注射的系统综述及meta分析[J].中华内分泌代谢杂志,2009,(4):450-453.
[11]TOKUHIRA N,KITAGISHI Y,SUZUKI M,et al.PI3K/AKT/PTEN pathway as a target for Crohn's disease therapy(Review)[J].Int J Mol Med,2015,35(1):10-16.