健脾清化方对2型糖尿病模型大鼠肝脏糖原合成的影响
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摘要
目的:探讨中药复方健脾清化方对2型糖尿病模型大鼠肝脏糖原合成的影响及机制。方法:采用Wistar大鼠高脂喂养联合小剂量链脲佐菌素(STZ)腹腔注射进行造模,随机数字表法分为正常组、模型组、健脾清化方组,连续4周灌胃给药,观察各组大鼠的随机血糖水平。灌胃4周后,处死大鼠,留取标本,过碘酸希夫氏(PAS)染色法观察各组大鼠肝脏糖原水平;Western Blot法测大鼠肝脏组织糖原合成相关酶糖原合成酶(GS)、糖原合成酶激酶3β(GSK3β)的表达及其磷酸化水平的表达。结果:与模型组比较,健脾清化方组能够降低大鼠的随机血糖(P<0.01),增加大鼠肝脏的糖原合成;且能够降低大鼠pGS/GS比值(P<0.01),增加pGSK3β/GSK3β的比值(P<0.01)。结论:健脾清化方能够增加大鼠肝脏GSK3β的磷酸化表达,降低GS的磷酸化表达,从而促进肝脏糖原合成,降低糖尿病大鼠的血糖。
Objective: To explore the effect of Jianpi Qinghua Foumula(JQF) on the synthesis of hepatic glycogen of type 2 diabetic(T2 DM) rats. Methods: T2 DM rats was induced in Wistar rats by high-fat diet feeding and small dose intraperitoneal injection streptozotocin(STZ). Rats were divided into 3 groups(normal group, model group, and JQF group) via random number table. They were given medicine for 4 weeks and observed random blood glucose weekly. PAS was performed to observe hepatic glycogen level of rats in each group. Western Blot was performed to assess differential expression of glycogen synthesis-related enzyme GS, GSK3β and phosphorylation of them. Results: Synthesis of glycogen was increased in JQF group comparing with model group(P<0.01), increased the glycogen synthesis in liver. Phosphorylation levels of PGS/GS were decreased(P<0.01), and phosphorylation levels of pGSK3β/GSK3β were enhanced in JQF group comparing with the model group(P<0.01). Conclusion: JQF could increase the phosphorylation expression of GSK3β in rat liver and decrease the phosphorylation expression of GS, thus promoting glycogen synthesis in liver and reducing blood sugar in T2 DM rats.
Objective: To explore the effect of Jianpi Qinghua Foumula(JQF) on the synthesis of hepatic glycogen of type 2 diabetic(T2 DM) rats. Methods: T2 DM rats was induced in Wistar rats by high-fat diet feeding and small dose intraperitoneal injection streptozotocin(STZ). Rats were divided into 3 groups(normal group, model group, and JQF group) via random number table. They were given medicine for 4 weeks and observed random blood glucose weekly. PAS was performed to observe hepatic glycogen level of rats in each group. Western Blot was performed to assess differential expression of glycogen synthesis-related enzyme GS, GSK3β and phosphorylation of them. Results: Synthesis of glycogen was increased in JQF group comparing with model group(P<0.01), increased the glycogen synthesis in liver. Phosphorylation levels of PGS/GS were decreased(P<0.01), and phosphorylation levels of pGSK3β/GSK3β were enhanced in JQF group comparing with the model group(P<0.01). Conclusion: JQF could increase the phosphorylation expression of GSK3β in rat liver and decrease the phosphorylation expression of GS, thus promoting glycogen synthesis in liver and reducing blood sugar in T2 DM rats.
引文
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[12]Maqbool M,Hoda N.GSK3 inhibitors in the therapeutic development of diabetes,cancer and neurodegeneration:past,present and future.Curr Pharm Des,2017,23(29):4332-4350
[13]Chandirasegaran G,Elanchezhiyan C,Ghosh K,et al.Effects of Berberine chloride on the liver of streptozotocin-induced diabetes in albino Wistar rats.Biomed Pharmacother,2018,99(3):227-236
[14]Tiwari P,Ahmad K,Baig M H,et al.Gymnema sylvestre for diabetes:From traditional herb to future’s therapeutic.Curr Pharm Des,2017,23(11):1667-1676
[15]Ezuruike U,Prieto J M.Assessment of potential herb-drug interactions among nigerian adults with type-2 diabetes.Front Pharmacol,2016,7(3):248-251
[16]徐隽斐,侯瑞芳,顾逸梦,等.健脾清化方对2型糖尿病(气阴两虚型)血糖波动的作用研究.辽宁中医杂志,2015,42(9):1674-1676
[2]Zheng Y,Ley S H,Hu F B.Global aetiology and epidemiology of type 2 diabetes mellitus and its complications.Nat Rev Endocrinol,2018,14(2):88-98
[3]Pham N,Eggleston K.Prevalence and determinants of diabetes and prediabetes among Vietnamese adults.Diabetes Research&Clinical Practice,2016,113:116-124
[4]徐隽斐,陈清光,侯瑞芳,等.健脾清化方对糖尿病模型大鼠血糖波动的影响.上海中医药大学学报,2017,31(3):71-74
[5]李俊燕,陶枫,陈清光,等.健脾清化方对2型糖尿病大鼠基因表达谱及信号通路的影响.中医杂志,2015,56(17):1498-1501
[6]李俊燕,顾逸梦,陈清光,等.健脾清化方调节肠道Th1和Th17免疫细胞型转录因子及炎症因子改善2型糖尿病大鼠胰岛素抵抗.中华中医药杂志,2018,33(7):2770-2772
[7]李俊燕,陶枫,陈清光,等.健脾清化方对糖尿病大鼠血液基因表达谱的影响.中华中医药杂志,2015,30(11):4070-4073
[8]Zhang Y,Lee F Y,Barrera G,et al.Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice.Proc Natl Acad Sci USA,2006,103(4):1006-1011
[9]Lee J,Kim M S.The role of GSK3 in glucose homeostasis and the development of insulin resistance.Diabetes Res Clin Pract,2007,77(1):49-57
[10]Copps K D,White M F.Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2.Diabetologia,2012,55(10):2565-2582
[11]Leng S,Zhang W,Zheng Y,et al.Glycogen synthase kinase3 beta mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate 1.J Endocrinol,2010,206(2):171-181
[12]Maqbool M,Hoda N.GSK3 inhibitors in the therapeutic development of diabetes,cancer and neurodegeneration:past,present and future.Curr Pharm Des,2017,23(29):4332-4350
[13]Chandirasegaran G,Elanchezhiyan C,Ghosh K,et al.Effects of Berberine chloride on the liver of streptozotocin-induced diabetes in albino Wistar rats.Biomed Pharmacother,2018,99(3):227-236
[14]Tiwari P,Ahmad K,Baig M H,et al.Gymnema sylvestre for diabetes:From traditional herb to future’s therapeutic.Curr Pharm Des,2017,23(11):1667-1676
[15]Ezuruike U,Prieto J M.Assessment of potential herb-drug interactions among nigerian adults with type-2 diabetes.Front Pharmacol,2016,7(3):248-251
[16]徐隽斐,侯瑞芳,顾逸梦,等.健脾清化方对2型糖尿病(气阴两虚型)血糖波动的作用研究.辽宁中医杂志,2015,42(9):1674-1676