脑小血管病患者血管内皮损伤标志物的变化及瑞舒伐他汀干预的影响

Changes of endothelial markers due to injury in cerebral small vessel disease and the effect of rosuvastatin intervention

目的探讨脑小血管病患者内皮素(endothelin,ET)、同型半胱氨酸(homocysteine,Hcy)、血管性血友病因子(von Willebrand factor,vWF)、血栓调节蛋白(thrombomodulin,TM)水平的变化及瑞舒伐他汀干预的影响。方法将2018年1月至2019年6月邯郸市第一医院体检中心80名健康体检者设为健康组(H组),将同期收治的240例脑小血管病(cerebral small vessel disease,CSVD)患者,随机分为试验1组(T1组)、试验2组(T2组)和对照组(C组),各80例。T1组口服瑞舒伐他汀5mg/次,1次/d;T2组口服瑞舒伐他汀10mg/次,1次/d;C组口服与瑞舒伐他汀外观相同安慰剂1片/次,1次/d;疗程6个月,分别测定4组总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)、ET、Hcy、vWF、TM,其中H组无治疗措施,只与其它3组治疗前指标进行比较,C组、T1组、T2组均测定治疗前后的指标,并进行比较。结果 H组与C组、T1组、T2组治疗前血脂水平比较差异均无统计学意义。C组治疗前、后血脂水平比较差异无统计学意义(P>0.05);T1组、T2组治疗后TC、LDL-C水平较治疗前明显下降(P<0.05),且T2组下降较T1组明显(P<0.05)。H组ET、Hcy、vWF、TM水平均低于C组、T1组、T2组治疗前水平,差异有统计学意义(P<0.05);C组治疗前、后ET、Hcy、vWF、TM水平比较差异无统计学意义(P>0.05);T1组、T2组治疗后ET、Hcy、vWF、TM水平较治疗前降低,差异有统计学意义(P<0.05);T2组各指标改善较T1组明显,差异有统计学意义(P<0.05)。结论 CSVD患者存在内皮功能损伤,瑞舒伐他汀可改善脑小血管病患者血管内皮功能,且其改善程度与剂量呈正相关。

Objective To investigate the changes of endothelin,homocysteine,von Willebrand factor and thrombomodulin levels in patients with cerebral small vessel disease and the effect of rosuvastatin intervention.Methods From January 2018 to June 2019,80 healthy individuals in the physical examination center of the First Hospital of Handan were selected as the healthy control group(H group).A total of 240 patients with cerebral small vessel disease(CSVD)who were treated at the same time were randomly divided into experimental group 1(T1 group),experimental group 2(T2 group),and control group(C group),80 patients in each group.T1 group was given rosuvastatin orally at 5 mg/time,once a day;T2 group was given rosuvastatin orally at 10 mg/time,once a day;group C was given oral placebo with the same appearance as that of rosuvastatin,once a day.After six months of treatment,serum levels of total cholesterol,triglyceride,high density lipoprotein cholesterol,low density lipoprotein cholesterol,endothelin,homocysteine,von Willebrand factor,and thrombomodulin were measured in all 4 groups.Among them,H group had no treatment and its serum levels were only compared with the pre-treatment measurements of other three groups.The index levels before and after treatment were measured and compared among C group,T1 group and T2 group.Results There was no significant difference in serum lipid level among the four groups before treatment,as well as in group C before and after treatment(P>0.05).The levels of TC and LDL-C after treatment in T1 group and T2 group were significantly lower than those before treatment(P<0.05);and the decrease in T2 group was more significant than that in T1 group(P<0.05).The levels of ET,Hcy,vWF and TM in group H were all lower than those in groups C,T1 and T2 before treatment(P<0.05).There were no significant differences in ET,Hcy,vWF and TM levels in group C before and after treatment(P>0.05).The ET,Hcy,vWF and TM levels in T1 group and T2 group decreased after treatment compared with those before treatment(P<0.05).The improvement of each index in T2 group was more significant than that in T1 group(P<0.05).Conclusion The endothelial function is impaired and can be improved by rosuvastatin in patients with Cerebral Small Vessel Disease.The degree of improvement was positively correlated with the dose.