强肝胶囊促进肝糖原合成降低大鼠高血糖的机制研究
Qiang-Gan Capsule reduces hyperglycemia via promoting liver glycogen synthesis in rats
- 上海中医药大学学报 2021年35卷第3期 页码：45-51
- 作者机构：
1.上海市宝山区中西医结合医院（上海 201999）
2.上海中医药大学附属龙华医院脾胃病研究所（上海 200032）
- 作者简介：
舒祥兵，男，博士，医师，主要从事中医药防治脂肪性肝病的基础与临床研究
张莉，研究员；E-mail：zhangli.hl@163.com
- 基金信息：国家自然科学基金资助项目(81804020)
DOI：10.16306/j.1008-861x.2021.03.009
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舒祥兵, 操颖, 顾晔, 等. 强肝胶囊促进肝糖原合成降低大鼠高血糖的机制研究[J]. 上海中医药大学学报, 2021,35(3):45-51.
SHU Xiangbing, CAO Ying, GU Ye, et al. Qiang-Gan Capsule reduces hyperglycemia via promoting liver glycogen synthesis in rats[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(3):45-51.
舒祥兵, 操颖, 顾晔, 等. 强肝胶囊促进肝糖原合成降低大鼠高血糖的机制研究[J]. 上海中医药大学学报, 2021,35(3):45-51. DOI： 10.16306/j.1008-861x.2021.03.009.
SHU Xiangbing, CAO Ying, GU Ye, et al. Qiang-Gan Capsule reduces hyperglycemia via promoting liver glycogen synthesis in rats[J]. Academic Journal of Shanghai University of Traditional Chinese Medicine, 2021,35(3):45-51. DOI： 10.16306/j.1008-861x.2021.03.009.
摘要
目的：,2,探讨强肝胶囊对高糖饮食诱导的高血糖大鼠的降糖效应及其作用机制。,方法：,2,雄性Wistar大鼠40只，随机分为正常组和高糖饮食组，分别给予普通饲料和高糖饲料。饲喂6周后，高糖饮食组大鼠随机分为模型组、吡格列酮（10 mg·kg,－1,·d,－1,）组、强肝胶囊低剂量（0.4 g·kg,－1,·d,－1,）组、强肝胶囊高剂量（1.2 g·kg,－1,·d,－1,）组，每组8只。各组灌胃给予相应药物，连续4周。末次给药后，取血，分离肝组织。生化分析仪检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）和空腹血糖（FBG）水平；ELISA检测糖化血红蛋白（HbA1c）和肝糖原含量；PAS染色后光镜下观察肝脏糖原分布；Western blot检测肝脏糖原合酶激酶3β（GSK3β）、糖原合酶（GS）、磷酸烯醇式丙酮酸羧激酶2（PCK2）、肝糖原磷酸化酶（PYGL）和葡萄糖-6-磷酸酶（G6PC）的蛋白表达。,结果：,2,①与模型组相比，强肝胶囊低、高剂量组血清ALT和AST水平显著降低（,P,<,0.01），强肝胶囊低剂量组HDL水平显著升高（,P,<,0.05），LDL水平显著降低（,P,<,0.05）。②与模型组相比，强肝胶囊低、高剂量组FBG和HbA1c水平显著降低（,P,<,0.05，,P,<,0.01），肝糖原含量明显升高（,P,<,0.05）。PAS染色观察显示，强肝胶囊干预后模型大鼠肝脏糖原着色面积明显增加。③模型组大鼠肝组织p-GSK3β/GSK3β和p-GS/GS蛋白表达比值较正常组显著升高（,P,<,0.05），而低剂量强肝胶囊干预可明显下调模型大鼠p-GSK3β/GSK3β和p-GS/GS蛋白表达比值（,P,<,0.05）。各组大鼠肝组织PYGL、PCK2和G6PC蛋白表达的比较，差异均无统计学意义（,P,>,0.05）。,结论：,2,强肝胶囊对高糖饮食诱导的高血糖大鼠具有降糖效应，其作用机制与增加肝糖原含量、降低糖原合成过程中GSK3β和GS磷酸化水平有关。
Abstract
Objective:,2,To investigate the hypoglycemic effects and mechanisms of Qiang-Gan Capsule on hyperglycemic rats induced by high sucrose diet.,Methods:,2,Forty male Wistar rats were randomly divided into the normal group and high sucrose diet group, which treated with normal diet and high sucrose diet, respectively.After feeding for 6 weeks, the rats in the high sucrose diet group were randomly divided into the model group, pioglitazone(10 mg·kg,-1,·d,-1,) group, Qiang-Gan Capsule low-dose(0.4 g·kg,-1,·d,-1,) group and high-dose(1.2 g·kg,-1,·d,-1,) group, 8 rats in each group.Each group was treated with the corresponding drug by intragastric administration for 4 weeks.After the last administration, blood was taken and liver tissue was separated.The serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglyceride(TG), total cholesterol(TC), high-density lipoprotein(HDL), low-density lipoprotein(LDL) and fasting blood glucose(FBG) were detected by biochemical analyzer, and the levels of glycosylated hemoglobin(HbA1c) and liver glycogen were detected by enzyme-linked immunosorbent assay(ELISA) .The distribution of liver glycogen was observed under light microscope after PAS staining.The protein expressions of glycogen synthase kinase 3β(GSK3β), glycogen synthase(GS), phosphoenolpyruvate carboxykinase2(PCK2), glycogen phosphorylase in liver(PYGL) and glucose-6-phosphatase(G6PC) were detected by Western blot.,Results:,2,①Compared with the model group, the serum ALT and AST levels were significantly decreased in the Qiang-Gan Capsule low-dose group and high-dose group(,P,<,0.01), and the HDL level in the Qiang-Gan Capsule low-dose group was significantly increased(,P,<,0.05), and the LDL level was significantly decreased(,P,<,0.05) .②Compared with the model group, the levels of FBG and HbA1c were decreased significantly in the Qiang-Gan Capsule low-dose group and high-dose group(,P,<,0.05,P,<,0.01), and the content of liver glycogen was significantly increased(,P,<,0.05) .PAS staining showed that the liver glycogen staining area of model rats was increased significantly after Qiang-Gan Capsule intervention.③The protein expression ratios of p-GSK3β/GSK3β and p-GS/GS in rat liver tissue of the model group were significantly higher than those of the normal group(,P,<,0.05), but Qiang-Gan Capsule at low-dose could obviously down-regulate the expression ratios of p-GSK3β/GSK3β and p-GS/GS in model rats(,P,<,0.05) .There were no statistically significant differences in the protein expressions of PYGL, PCK2 and G6PC in liver tissue of rats among these groups(,P,>,0.05) .,Conclusion:,2,Qiang-Gan Capsule shows hypoglycemic effects on hyperglycemic rats induced by high sucrose diet, and its mechanism is related to the increase of liver glycogen content and the decrease of GSK3β and GS phosphorylation during glycogen synthesis.
关键词
强肝胶囊高血糖肝糖原糖原合酶大鼠
Keywords
Qiang-Gan Capsulehyperglycermialiver glycogenglycogen synthaserat
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