丹参多酚酸盐对动脉粥样硬化大鼠血流动力学和血液流变学的影响

Influence of salvianolate on hemodynamics and hemorrheology in rats with atherosclerosis

目的分析丹参多酚酸盐对动脉粥样硬化大鼠血流动力学和血液流变学的影响。方法将96只实验用SD大鼠随机分为正常对照组,模型组,丹参多酚酸盐低剂量组60 mg/(kg·d)、中剂量组120mg/(kg·d)、高剂量组240 mg/(kg·d)和辛伐他汀组2 mg/(kg·d),各组均16只。采用高脂饲料喂养结合腹腔注射维生素D3的方法建立大鼠动脉粥样硬化模型,通过超声检查确定模型成功。丹参多酚酸盐各组和辛伐他汀组分别灌胃给药,正常对照组和模型组则同步给予等体积生理盐水,疗程12周。分别测定各组大鼠左心室内压最大上升速率(lv+dp/dtmax)和心室内压达峰时间(t-dp/dtmax)以及全血黏性(低切、中切、高切)、血浆黏度、红细胞压积和血小板黏附率。测定血脂指标,总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)。采用HE染色观察主动脉形态结构并进行病变分级。结果模型组lv+dp/dtmax较正常对照组显著降低,t-dp/dtmax较正常对照组显著延长,差异有统计学意义(P均<0.01)。与模型组比较,丹参多酚酸盐中剂量组和高剂量组lv+dp/dtmax提高,t-dp/dtmax缩短,差异有统计学意义(P均<0.05)。模型组全血黏度(低切、中切、高切)、血浆黏度、红细胞压积、血小板黏附率较正常对照组均显著升高,差异有统计学意义(P均<0.05)。与模型组比较,丹参多酚酸盐中剂量组和高剂量组血浆粘度、红细胞压积显著降低,其中高剂量组全血黏度(低切、中切、高切)、血小板黏附率均显著降低,差异有统计学意义(P均<0.05)。与正常对照组比较,模型组TC、TG、LDL-C水平均显著升高,而HDL-C显著降低,差异有统计学意义(P均<0.05)。与模型组比较,中剂量组和高剂量组TC、TG、LDL-C水平显著降低,其中高剂量组HDL-C显著升高,差异有统计学意义(P均<0.05)。病变分级结果:模型组大鼠主动脉病变2级及以上共14例(87.5%),正常对照组分级均为0级;丹参多酚酸盐高剂量组2级以下12例(75.0%)。结论中、高剂量丹参多酚酸盐明显改善动脉粥样硬化大鼠血液流变学指标和血液动力学指标,发挥保护作用。

Objective To analyze the influence of salvianolate on hemodynamics and hemorrheology in rats with atherosclerosis.Methods SD rats(n=96)were randomly divided into normal control group,model group,lowdose salvianolate group[60mg/(kg·d)],mid-dose salvianolate group[120mg/(kg·d)],high-dose salvianolate group[240mg/(kg·d)]and simvatatin group[2mg/(kg·d),each n=16].The rat model of atherosclerosis was established through feeding high-fat forage and intraperitoneally injecting VD3,and successful model was determined by using ultrasound examination.The salvianolate groups and simvatatin group were respectively given corresponding drugs orally,and meanwhile normal control group and model group were given normal saline in the same volume for12weeks.The changes of lv+dp/dtmax,t-dp/dtmax,whole blood viscosity(WBV,high,medium and low share rates),plasma viscosity,hematocrit(Hct)and platelet adhesiveness rate were detected respectively.The indexes of blood fat were detected,including total cholesterol(TC),triglyceride(TG),low-density lipoproteincholesterol(LDL-C)and high-density lipoprotein-cholesterol(HDL-C).The aortic morphological structure was observed through HE staining and lesions were graded.Results The level of lv+dp/dtmax decreased significantly and level of t-dp/dtmax increased significantly in model group compared with normal control group(all P<0.01).The level of lv+dp/dtmax increased and level of t-dp/dtmax decreased in mid-dose salvianolate group and highdose salvianolate group compared with model group(all P<0.05).The indexes of WBV(high,medium and low share rates),plasma viscosity,Hct and platelet adhesiveness rate increased significantly in model group compared with normal control group(all P<0.05).The indexes of plasma viscosity and Hct decreased significantly in mid-dose salvianolate group and high-dose salvianolate group,and WBV(high,medium and low share rates)and platelet adhesiveness rate decreased significantly in high-dose salvianolate group compared with model group(all P<0.05).The levels of TC,TG and LDL-C increased significantly,and level of HDL-C decreased significantly in model group compared with normal control group(all P<0.05).The levels of TC,TG and LDL-C decreased significantly in mid-dose salvianolate group and high-dose salvianolate group,and level of HDL-C increased significantly inhigh-dose salvianolate group compared with model group(all P<0.05).The results of lesion grading showed that there were14rats(87.5%)with grade2or higher aortic lesions in model group.The lesion grading was0in normal control group,and there were12rats(75.0%)with grade2or lower aortic lesions in high-dose salvianolate group.Conclusion Salvianolate in high or medium doses can play a protective role through significantly improving the indexes of hemodynamics and hemorrheology in rats with atherosclerosis.