藻酸双酯钠对2型糖尿病心血管并发症防治作用的研究

目的观察藻酸双酯钠(PSS)对2型糖尿病并发的心血管疾病危险因素的影响,并探讨其可能机制。方法高糖高脂饮食加小剂量链脲佐菌素(STZ 20mg·kg-1)制作2型糖尿病Wister大鼠模型,并将其随机平均分为5组:正常对照(NC)组、模型(Mod)组、藻酸双酯钠(PSS)组、二甲双胍(Met)组、洛伐他汀(Lov)组,并给予相应的药物治疗8wk。实验过程中观察血糖、血脂的变化;发色底物法检测血清中组织纤溶酶原激活物(t-PA)、组织纤溶酶原激活抑制物(PAI-1)的活性;22wk后处死大鼠,取其主动脉,透射电镜观察主动脉的超微结构;免疫组织化学及Western blot方法检测动脉内核转录因子(NF-κB)及细胞间粘附分子(ICAM-1)的表达水平。结果PSS组的空腹血糖(FBG)、血脂(TG、TC、LDL)水平及PAI-1的活性均明显低于模型组(P<0.05),而t-PA的活性则明显高于模型组(P<0.05);同时PSS组NF-κB和ICAM-1的表达比模型组明显减少(P<0.05);PSS组主动脉损伤明显轻于模型组。结论藻酸双酯钠能抑制2型糖尿病大鼠并发的心血管疾病的发生、发展,其机制可能与其降低血糖、血脂水平,改善t-PA和PAI-1的活性,抑制核因子NF-κB的活化及细胞间粘附分子ICAM-1的表达有关。

Effects of polysaccharide sulfate on cardiovascular diseases induced by type 2 diabetes

Aim To explore the pharmacological mechanism and the effects of polysaccharide sulfat(PSS) on cardiovascular diseases induced by type 2 diabetes mellitus(DM) through observing the risk factors.Methods Type 2 diabetic animal model was established by high-sugar and high-fat diets,combined with injection of small amount streptozotocin(STZ 20 mg·kg-1,iv).Adult male wistar rats were divided into five groups: normal control group,model group,polysaccharide sulfate group,metformin group and lovastatin group.They were treated with exact medicne for 8 weeks,but control group and model group were treated with 0.9% Nacl.During this process,FBG and serum lipid concentrations were measured.22 weeks later,the rats were sacrificed.The activity of tissue-type plasminogen activator(t-PA) and plasminogen activator inhibitor type-1(PAI-1) were detected by chemical methods.The aortas were collected for histopathlogical,immunohistochemical and Western blot studies.Results FBG concentrations and serum lipid(TC,TG,LDL) levels decreased in PSS group as compared from those of model group(P<0.05);the activity of t-PA and PAI-1 in PSS group were remarkably different from those of model group(P<0.05);nuclear factor kappa B(NF-κB) activation and intercellular adhesion molecule(ICAM-1) expression level of the aortas in the model group were significantly higher than those of PSS group(P<0.05).Conclusions PSS could prevent cardiovascular diseases through alleviating the damage to the arterial wall by decreasing the FBG concentrations,serum lipid levels,regulating the activity of t-PA and PAI-1,and inhibiting NF-κB activation and ICAM-1 expression.