基于p-Akt/p-GSK3β/GSK3β通路灵芝多糖对糖尿病大鼠心肌重构及保护作用研究  

Myocardial remodeling and protective effects of ganoderma lucidum polysaccharide based on p-Akt/p-GSK3β/GSK3β pathway in diabetic rats

作　　者：牛尚梅[1] 王丽萍[1] 杨英焘 宋潇萌 胡新磊[1] NIU Shangmei;WANG Liping;YANG Yingtao;SONG Xiaomeng;HU Xinlei(The Second Department of Endocrinology,Handan First Hospital,Handan,Hebei 056002,China;The Fourth Department of Cardiology,Handan First Hospital,Handan,Hebei 056002,China)

机构地区：[1]邯郸市第一医院内分泌二科,河北邯郸056002 [2]邯郸市第一医院心内四科,河北邯郸056002

出　　处：《安徽医药》2023年第12期2361-2366,共6页Anhui Medical and Pharmaceutical Journal

基　　金：2021年度河北省医学科学研究课题(20211123)。

摘　　要：目的探讨灵芝多糖(GLP)通过磷酸化丝氨酸/苏氨酸激酶(p-Akt)/磷酸化糖原合成酶激酶-3β(p-GSK3β)/糖原合成酶激酶-3β(GSK3β)通路对糖尿病大鼠心肌重构的影响。方法于2020年12月至2021年12月,将90只SPF级雄性SD大鼠,按照随机数字表法分为对照组、模型组、GLP低、中、高剂量组,各18只。模型组和GLP各剂量组采用高脂高糖饲料喂养联合腹腔注射小剂量链脲佐菌素(STZ)溶液(30 mg/kg)诱导糖尿病大鼠模型,各组取建模成功的15只大鼠用于实验。GLP低、中、高剂量组均按照10 mL/kg体质量,灌胃浓度25、50、100 mg/kg GLP生理盐水溶液,对照组和模型组给予等体积生理盐水,每天1次,连续4周。比较各组大鼠血糖、体质量、左心室指数、心肌纤维化水平、心肌细胞凋亡水平、心肌组织中转化生长因子-β1(TGF-β1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)水平以及p-Akt、丝氨酸/苏氨酸激酶(Akt)、p-GSK3β、GSK3β蛋白表达水平差异。结果与对照组的血糖(4.45±0.38)mmol/L、左心室指数(2.21±0.18)、胶原容积分数(CVF)(2.59±0.27)%、凋亡指数(2.17±0.24)%和心肌组织TGF-β1(126.34±10.43)μg/L、MMP-2(141.23±12.12)μg/L、MMP-9(126.34±10.23)μg/L水平比较,模型组[(20.34±2.78)mmol/L、3.46±0.23、(16.12±1.43)%、(20.32±1.78)%、(257.65±18.15)μg/L、(268.43±19.3)μg/L、(347.65±23.15)μg/L],GLP低剂量组[(16.36±1.12)mmol/L、3.17±0.21、(13.17±1.27)%、(15.31±1.15)%、(214.46±17.44)μg/L、(227.18±17.36)μg/L、(302.46±23.48)μg/L],中剂量组[(13.23±0.97)mmol/L、2.84±0.18、(10.41±0.96)%、(12.18±1.02)%、(184.44±14.37)μg/L、(189.68.±16.89)μg/L、(257.44±19.77)μg/L]和高剂量组[(9.84±1.01)mmol/L、2.57±0.16、(7.36±0.62)%、(9.66±0.74)%、(163.17±11.54)μg/L、(152.74±15.23)μg/L、(176.17±12.45)μg/L]显著升高,大鼠体质量和p-Akt、p-GSK3β蛋白水平均显著降低(P<0.05);与模型组比较,GLP各剂量组血糖、左心室指�Objective To investigate the effect of ganoderma lucidum plysaceharide(GLP)on myocardial remodeling through the phospho-serine/threonine kinase(p-Akt)/phospho-glycogen synthase kinase-3β(p-GSK3β)/glycogen synthase kinase-3β(GSK3β)pathway in diabetic cardiomyopathy rats.Methods From December 2020 to December 2021,90 SPF male SD rats were assigned into control,model,low-,medium-,high-dose GLP groups according to random number table method,18 rats in each group.The model group and GLP groups were fed with high-fat and high-sugar diet combined with intraperitoneal injection of low dose of streptozocin(STZ)solution(30 mg/kg)to induce diabetic cardiomyopathy rats model,15 rats successfully modeled for experiments in each group.The low-,medium-and high-dose GLP groups were given 25,50 and 100 mg/kg GLP solution(saline)by gavage according to the body weight of 10 mL/kg.The rats in the control group and the model group were given equal volume of saline solution daily for 4 weeks.A comparison was made of blood glucose,body weight,left ventricular index,myocardial fibrosis levels,myocardial apoptosis levels,transforming growth factor-β1(TGF-β1)in myocardial tissue,matrix metallopeptidase-2(MMP-2),matrix metalloproteinase-9(MMP-9)levels,and p-Akt,serine/threonine kinase(Akt),p-GSK3β,GSK3β protein expression levels.Results Compared with blood glucose,left ventricular index,collagen volume fraction(CVF),apoptosis index(AI)and myocardial TGF-β1,MMP-2,and MMP-9 levels[(4.45±0.38)mmol/L,(2.21±0.18),(2.59±0.27)%,(2.17±0.24)%,(126.34±10.43)μg/L,(141.23±12.12)μg/L,(126.34±10.23)μg/L]in the control group,the above indicators in the model group[(20.34±2.78)mmol/L,(3.46±0.23),(16.12±1.43)%,(20.32±1.78)%,(257.65±18.15)μg/L,(268.43±19.3)μg/L,(347.65±23.15)μg/L],the low-dose GLP group[(16.36±1.12)mmol/L,(3.17±0.21),(13.17±1.27)%,(15.31±1.15)%,(214.46±17.44)μg/L,(227.18±17.36)μg/L,(302.46±23.48)μg/L],the middle-dose GLP group[(13.23±0.97)mmol/L,(2.84±0.18),(10.41±0.96)%,(12.18±1.02)%,(184.44±14.3

关 键 词：灵芝 糖尿病心肌病 心肌重构 丝氨酸/苏氨酸激酶 糖原合成酶激酶-3Β 大鼠 Sprague-Dawley 

分 类 号：R285.5[医药卫生—中药学]