藻酸双酯钠对2型糖尿病心血管并发症防治作用的研究  

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

作　　者：于丽凤[1] 赵金生[2] 于龙[3] 赵美眯[2] 齐贺[2] 李智[2] 

机构地区：[1]中国医科大学临床医药学院医学基础教研室,辽宁沈阳110002 [2]中国医科大学药学院天然药物研究室,辽宁沈阳110001 [3]沈阳第一制药厂,辽宁沈阳110023

出　　处：《中国药理学通报》2008年第5期630-635,共6页Chinese Pharmacological Bulletin

摘　　要：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。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, mefformin 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 decreased in PSS group model group （ P 〈 O. 05 ） lipid （ TC, TG, LDL） levels as compared from those of the activity of t-PA and PAI- 1 in PSS group were remarkably different from those of model group（ P 〈 O. 05 ） ; nuclear factor kappa B （ NF- KB ） 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 〈 O. 05 ）. Conclusions PSS could prevent cardio- vascular 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-KB activation and ICAM-1 expression.

关 键 词：藻酸双酯钠 2型糖尿病心血管并发症 核转录因子 细胞间粘附分子 组织纤溶酶原激活物 

分 类 号：R-332[医药卫生] R282.77