文章摘要
牛尚梅,王丽萍,杨英焘,等.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[J].安徽医药,2023,27(12):2361-2366.
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
  
DOI:10.3969/j.issn.1009-6469.2023.12.007
中文关键词: 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
英文关键词: Glossy ganoderma  Diabetic cardiomyopathy  Ventricular remodeling  Serine/threonine kinase  Glycogen syn. thase kinase-3β  Rats, Sprague-Dawley
基金项目:2021年度河北省医学科学研究课题( 20211123)
作者单位E-mail
牛尚梅 邯郸市第一医院内分泌二科河北邯郸 056002  
王丽萍 邯郸市第一医院内分泌二科河北邯郸 056002  
杨英焘 邯郸市第一医院心内四科河北邯郸 056002  
宋潇萌 邯郸市第一医院内分泌二科河北邯郸 056002  
胡新磊 邯郸市第一医院内分泌二科河北邯郸 056002 15081769283@163.com 
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中文摘要:
      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/L2.46±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)%、、(30,(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、左心室指数、 CVF、凋亡指数和心肌组织 TGF-β1、MMP-2、MMP-9水平均显著降低,大鼠体质量和 p-Akt、p-GSK3β蛋白水平均显著增加( P<0.05);血糖、左心室指数、心肌组织 CVF、凋亡指数和 TGF-β1、MMP-2、MMP-9水平与 GLP呈剂量依赖性降低,体质量、 p-Akt、p-GSK3β蛋白水平与 GLP呈剂量依赖性增加( P<0.05)。结论 GLP能够降低 DCM大鼠血糖、减轻心肌纤维化和心肌细胞凋亡,可能是通过激活 p-Akt/p-GSK3β/GSK3β通路中相关蛋白表达发挥调控作用。
英文摘要:
      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 modelgroup 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 bodyweight 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. Acomparison 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-β 1, 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] inthe 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±14.37) μg/L, (189.68±16.89) μg/L, (257.44±19.77) μg/L], and the high-dose GLP group [(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] .were significantly increased, and rat body weight and p-Akt, p-GSK3β protein levels were significantly decreased (P< 0.05). Compared with model group, blood glucose, left ventricular index, CVF, AI, TGF-β1, MMP-2, and MMP-9 levels in the different GLP groups were significantly decreased, and rat body weight and p-Akt, p-GSK3β protein levels were significantly increased (P< 0.05). Blood glucose, left ventricular index, CVF, AI and TGF-β1, MMP-2, MMP-9 levels were decreased with GLP dose concentration, and rat body weight, p-Akt, p-GSK3β protein levels were increased with GLP dose concentration.Conclusion GLP can reduce DCM rats' blood sugar and weaken myocardial fibrosis and myocardial apoptosis, which may play a regulatory role by activation of relatedprotein expression in the p-Akt/p-GSK3β/GSK3β pathway.
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