机构地区:[1]中山大学附属第三医院心内科,广东广州510630 [2]中山大学附属第五医院心内科,广东珠海519000
出 处:《热带医学杂志》2021年第3期261-265,275,F0003,共7页Journal of Tropical Medicine
基 金:广东省自然科学基金(2016A030313841)。
摘 要:目的探究人参皂苷Rb1(GRb1)对糖尿病大鼠心脏功能、心肌细胞凋亡的影响及其机制。方法5~6周龄SPF级SD雄性大鼠24只,随机分为对照组、糖尿病组、糖尿病+低剂量GRb1(10 mg/kg)组和糖尿病+高剂量GRb1(20 mg/kg)组,每组6只。除对照组外,其他组大鼠腹腔注射40 mg/kg链脲佐菌素(STZ),1周后随机血糖大于16.7 mmol/L即为建模成功。糖尿病+低、高剂量GRb1组每天分别腹腔注射10、20 mg/kg GRb1,连续8周。通过左心室插管测定心功能,测定血清胰岛素(INS)、随机血糖(Glu)水平,计算胰岛素抵抗的稳态模型评估的对数值(lg HOMA-IR)。测定凋亡及炎症相关蛋白的表达:Bax/Bcl-2、裂解的半胱氨酸-天冬氨酸特异性蛋白酶3(cleaved caspase3)、p-核转录因子κB(NF-κB)/NF-κB、p-核转录因子κB的抑制蛋白(IκB)/IκB及沉默信息调节因子2相关酶1(sirt1),原位末端标记法(TUNEL)染色测定凋亡。结果STZ处理后大鼠随机血糖均高于16.7 mmol/L,模型构建成功。与对照组比较,糖尿病组大鼠左室舒张功能减退,差异有统计学意义(P<0.05),GRb1未能显著改善心功能。GRb1不影响糖尿病大鼠INS、Glu和lg HOMA-IR。与糖尿病组大鼠比较,糖尿病+低、高剂量GRb1组大鼠心肌组织中Bax/Bcl-2、cleaved caspased-3蛋白的表达以及NF-κB磷酸化、乙酰化水平显著降低,差异均有统计学意义(P<0.05)。与糖尿病组大鼠比较,糖尿病+高剂量GRb1组大鼠p-IκB/IκB水平显著降低,sirt1表达水平显著提高,差异均有统计学意义(P<0.05)。结论GRb1可以显著改善糖尿病大鼠心肌细胞的凋亡,改善糖尿病心肌病的预后。Objective To investigate the effects and mechanisms of ginsenoside Rb1(GRb1)on cardiac function and cardiocyte apoptosis in diabetes rats.Methods 24 Sprague-Dawley rats aged 5-6 weeks were randomly divided into control group,diabetes group,diabetes+low-dose GRb1(10 mg/kg)group and diabetes+high-dose GRb1(20 mg/kg)group,with 6 rats in each group.The rats except the control group were intraperitoneally injected with 40 mg/kg streptozotocin(STZ)by12 hours after the completion of the quarantine.One week later,when the random blood glucose level was higher than 16.7 mmol/L,the diabetic rat model was established successfully.GRbl was injected every day from intraperitoneally at the concentrations of 10 and 20 mg/kg for 8 weeks.Eight weeks later,the cardiac functions of the rats were measured by ventricular intubation.Insulin(INS)levels,blood glucose(Glu)and homeostasis model assessment of insulin resistance lg(lg HOMA-IR)were measured.Bax/Bcl-2,cleaved cysteinyl aspartate-specific proteinase 3(cleaved caspase 3),p-nuclear factor kappa B(NF-κB)/NF-κB,p-inhibitor of nuclear factor kappa B(IκB)/IκB and silent information regulator factor 2-related enzyme 1(sirt1)were measured by Western blot.Apoptosis was determined by terminal deoxynucleotidyl transferasemediated dUTP-biotin nick end labeling assay(TUNEL)staining.Results After STZ treatment,the random blood glucose of rats was higher than 16.7 mmol/L,and the model was established successfully.Left ventricular diastolic function was impaired in diabetes rats;the difference was statistically significant(P<0.05).GRb1 did not changed cardiac function significantly when compared with the control group.GRbl did not affect parameters of INS,Glu and lg HOMA-IR in diabetic rats.Compared with the diabetes group,diabetes+low-dose GRb1 group and diabetes+high-dose GRbl group decreased the ratio of Bax/Bcl-2 and the expression of cleaved caspased-3(P<0.05).Meanwhile,the levels of NF-κB phosphorylation and acetylation were also reduced,the differences were statistically significa
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