复方丹参注射液对2型糖尿病患者血管内皮功能的影响

摘要

目的:观察2型糖尿病患者应用复方丹参注射液后颈动脉内-中膜厚度、肱动脉内皮依赖性舒张功能以及血清一氧化氮及内皮素1水平的变化,探讨复方丹参注射液对2型糖尿病患者血管内皮功能的影响.方法:①选择2003-10/2004-10菏泽市立医院内分泌科门诊和住院糖尿病患者102例,男58例,女44例,均对实施方案知情同意.将入选的糖尿病患者随机分为2组:糖尿病治疗组68例和糖尿病对照组34例.选择本院体检健康者50人为健康对照组,男24人,女26人;均自愿参加本实验.②糖尿病治疗组:在降糖药物应用的基础上给予复方丹参注射液40mL,溶解于生理盐水250mL中静滴,1次/d.糖尿病对照组:在降糖药物应用的基础上给予维生素C 2 g加入生理盐水250 mL中静脉滴注,1次/d,疗程4周.③颈动脉内-中膜厚度的测定采用AcusonSeguia 512型全数字化彩色多普勒超声仪,测定颈动脉内径,计算颈动脉内-中膜厚度与内径的比率.④使用惠普公司超声诊断仪进行非创伤性血管内皮功能的测定.反应性充血肱动脉内径变化率(%)=(血流介导的肱动脉内径-安静时肱动脉内径)/安静时肱动脉内径×100%.含硝.酸甘油后肱动脉内径变化率(%)=(含服硝酸甘油后肱动脉内径-安静时肱动脉内径)/安静时肱动脉内径×100%.整个试验由同一经验丰富的影像学科医生进行单盲操作.⑤血清学指标的测定:内皮素1水平测定采用放射免疫法,试剂盒由北京东亚免疫技术研究所提供.一氧化氮水平测定采用硝酸还原法测定,试剂盒由南京聚力生物医学工程研究所提供.⑥计量资料组间差异比较采用配对t检验,各指标间的相关性处理采用直线相关分析.结果:2型糖尿病患者102例和健康体检者50人均进入结果分析.颈动脉内-中膜厚度和颈动脉内-中膜厚度与内径比率:糖尿病患者治疗前均明显大于健康对照组(t=2.816 1～6.824 3,P<0.01),糖尿病治疗组患者治疗后均明显小于治疗前和糖尿病对照组治疗后(t=2.085 9～9.6491,P<0.01).②反应性充血肱动脉内径变化率、含硝酸甘油后肱动脉内径变化率及血清一氧化氮水平:糖尿病患者治疗前明显低于健康对照组(t=7.161 2～8.952 8,P<0.01).③血清内皮素1水平:糖尿病患者治疗前明显高于健康对照组(t=9.135 3,8.952 8,P<0.01),糖尿病治疗组治疗后明显低于治疗前和糖尿病对照组治疗后(t=6.757 4,3.048 1,P<0.01).④反应性充血肱动脉内径变化率、血清一氧化氮水平:糖尿病治疗组治疗后明显高于治疗前和糖尿病对照组治疗后(t=3.013 1～7.973 1,P<0.01).⑤相关性分析结果:反应性充血肱动脉内径变化率与血清一氧化氮水平呈显著正相关(r=0.411,P<0.01),与颈动脉内-中膜厚度呈显著负相关(r=-0.307,P<0.05);血清一氧化氮水平与颈动脉内-中膜厚度呈显著负相关(r=-0.336,P<0.05).结论:①糖尿病患者存在动脉粥样硬化和血管内皮功能失调的病理改变,具血管内皮功能失调可能与血清一氧化氮水平有关.②复方丹参注射液治疗2型糖尿病患者,可以逆转或延迟颈动脉内-中膜厚度增加的进程,改善血管内皮功能.%BACKGROUND The effect of lipid-regulating therapy has been affirmed definitely in the first and second grade prevention of coronary arteriosclerotic cardiopathy, and Ginkgo biloba extract has a certain effect to lower blood lipid.OBJECTIVE: To investigate the effect of new Ginkgo biloba extract recipe (NGBR) on the blood-lipid level and the degree of hepa tic fatty degeneration in experimental hyperlipidemic rats. DESIGN:A randomized and controlled trial.SETTING: Department of Cardiology , Jinshan Hospital of Fudan University; Suzhou Institute of Traditional Chinese Medicine, Department of Pharmacology, Soochow University,MATERIALS: A total of 60 SD rats of clean grade, after one week adaptive feeding, were randomly divided into six groups: normal control group, hyperlipidemic model group, NGBR 20 mg/(kg·d), 40 mg/(kg·d)and 80 mg/(kg·d) groups, as well as lipanthyl 25 mg/(kg·d)group, with 10 in each group. 10METHODS: The rats in lipanthyl 25 mg/(kg·d), NGBR 20 mg/(kg·d), 40 mg/(kg·d) and 80 mg/(kg·d) groups were by gavage administrated 10 mL/kg, at 9:00-10:00 every morning; while the rats in normal control group and hyperlipidemic model group were given distilled water of the same volume. Except for the rats in normal control group, the rats in other five groups were by gavage given fatty emulsion 10 mL/kg, at 1:00-2:00every afternoon for 28 days consecutively. On the 29th day, all the rats were tested on serum total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), apolipoprotein AI (apoAI) and apolipoprotein B (apoB); at the same time the lives of the rats were taken out for pathological.examination of the degree of hepatic fatty degeneration. MAIN OUTCOME MEASURES:The blood-lipid changes and the degree of hepatic fatty degeneration of rats in each group RESULTS:Totally 60 rats involved all entered the final result analysis. ① Comparison of blood-lipid changes of rats in each group: The levels of TC and low density lipoprotein cholesterol (LDL-C) in hyperlipidemic model group were obviously increased, HDL-C level was decreased, as compared with those in normal control group there was a significant difference (P < 0.01); but the TG level was only slightly increased (P > 0.05). In the three NGBR groups the levels of TC, TG and LDL-C were obviously decreased(P < 0.05 or 0.01 ), and the levels of HDL-C, apoAI and apoB were increased to a certain grade, with in the NGBR 80 mg/(kg·d)group the difference being obvious(P < 0.05). ② Comparison of the degree of hepatic fatty degeneration of rats in each group: In pathological examination, the liver of rats in hyperlipidemic model group presented diffuse fat vacuoles; in NGBR 40 and 80 mg/(kg·d)groups, the degeneration levels reduced to a given degree, especially obvious in NGBR 80 mg/(kg· d)group. CONCLUSION:NGBR can effectively correct the lipid metabolism in hyperlipidemia, with a good preventive role to hyperlipidemia induced by feeding fatty emulsion.