速效救心丸对动脉粥样硬化防治作用及其机制研究
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摘要
目的:本实验通过建立大鼠动脉粥样硬化(Atherosclerosis,AS)模型,观察速效救心丸对AS的预防性干预作用,并探讨速效救心丸的抗AS的作用及其可能的作用机制。
方法:采用高脂饮食加大剂量钙负荷(一次性腹腔注射维生素D_360万U/kg)方法建立大鼠AS模型。选用健康雄性成年Sprague-Dawlay(SD)大鼠50只,随即分为5组:①正常对照组(N):普通饲料;②模型组(M):高脂饲料;③速效救心丸低剂量治疗组(SXL):高脂饲料+SX60mg·kg~(-1)·d~(-1);④速效救心丸中剂量治疗组(SXM):高脂饲料+SX600mg·kg~(-1)·d~(-1);⑤速效救心丸高剂量治疗组(SXH):高脂饲料+SX1800mg·kg~(-1)·d~(-1);各治疗组药物自造模第一天开始灌胃给予,正常对照组和模型组给予等量生理盐水灌胃,共饲养12周。生化方法测定血清中丙二醛(malondialdehyde,MDA)的含量及超氧化物歧化酶(superoxidedismutase,SOD)的活性;高效液相色谱法加荧光测定同型半胱氨酸(homocysteine,Hcy)及不对称二甲基精氨酸(asymmetric dimethylarginine,ADMA)含量
结果:
1.超氧化物歧化酶、丙二醛:模型组大鼠血清中SOD活性明显低于正常组,差异有统计学意义(P＜0.05),MDA含量显著高于正常组(P＜0.05),速效救心丸预防组中低剂量组对SOD活性、MDA含量影响不明显,差别没有统计学意义(P＞0.05):中、高剂量组能升高SOD活性、降低MDA含量,与模型组相比,差别有统计学意义(P＜0.05)。
2.同型半胱氨酸:模型组大鼠血清Hcy含量高于对照组,两者差异有统计学意义(p＜0.05),速效救心丸低剂量组血清Hcy含量比模型组低,但差异没有统计学意义(p＞0.05),速效救心丸中、高剂量及均能明显降低各组大鼠血清中Hcy含量,各组与模型组相比,差异均有统计学意义(p＜0.05)。
3.不对称二甲基精氨酸:模型组大鼠血清ADMA含量高于对照组,两者差异有统计学意义(p＜0.05),速效救心丸低剂量组血清ADMA含量比模型组低,差异有统计学意义(p＜0.05),速效救心丸中、高剂量均能明显降低各组大鼠血清中ADMA含量,各组与模型组相比,差异均有统计学意义(p＜0.05)。
结论:高脂饮食加一次性大??维生素D_3负荷共同作用可成功建立大鼠早期AS模型。速效救心丸具有降血脂、抗脂质过氧化等抑制AS的形成的作用,其可能的机制是:(1)速效救心丸可降低AS大鼠血清MDA,升高SOD水平;(2)速效救心丸可以降低血清中Hcy水平;(3)速效救心丸可以降低血清中ADMA水平。本试验还证实动脉粥样硬化时同型半胱氨酸和不对称二甲基精氨酸确实存在正相关,为进一步探索动脉粥样硬化发病机制提供了理论依据。
Objective:To investigate the anti-atherosclerosis effects of SuXiao JiuXin Wan and its possible mechanism through animal model of experimental atherosclerosis.
Method:Experimental atherosclerosis in rats was produced by feeding with atherogenic-diet and vitamin D_3 administration(600,000 IU/kg by intraperitoneal injected at one time) for 12 weeks.50 male mature Sprague-Dawlay rats were divided into 5 groups randomly and equally:1.normal group(normal diet);2.AS model group (atherogenic-diet);3.SXL group(atherogenic-diet and SX 60mg·kg~(-1)·d~(-1));4.SXM group(atherogenic-diet and SX 600mg·kg~(-1)·d~(-1));5.SXH group(atherogenic-diet and SX 1800mg·kg~(-1)·d~(-1));SX was given by gavage from the beginning of the first week to the end of the experiment.At the same time,normal saline was given to the rats of normal group and model group with the same volume and the same way.After 12 weeks treatment,all rats were killed.Blood was collected to detect the levels of serum levels of malondialdehyde(MDA) and superoxide dismutase(SOD) by biochemistry method.The serum levels of homocysteine(Hcy) and asymmetric dimethylarginine(ADMA) were mearsured by high-performance liquid chromatography(HPLC) method.
Results:
1.In the model group,the serum SOD activity was declined and the MDA level was increased compared with the normal group(P＜0.05).Compared with the model group,the serum SOD and MDA level did not change appreciably in the SXL group(P＞0.05),while the serum SOD activity was increased and the MDA level was decreased definitely in the SXM,SXH groups(P＜0.05).
2.In the model group,the serum Hcy level was increased compared with the normal group(P＜0.05).Compared with the model group,the serum Hey level did not change appreciably in the SXL group(P＞0.05),while the serum Hcy level was decreased definitely in the SXM、SXH groups(P＜0.05).
3.In the model group,the serum ADMA level was increased compared with the normal group(P＜0.05).Compared with the model group,the serum ADMA level was changed appreciably in the SXL group(P＜0.05),and the serum ADMA level was decreased definitely in the SXM、SXH groups(P＜0.05).
Conclusions:The rat model of early atherosclerosis can be established successfully by atherogenic-diet and vitaminD3 administration(600,000 IU/kg by intraperitoneal injected at one time).The results suggest that the SuXiao JiuXin Wan can ameliorate the atherosclerotic changes and its protection effect may be involve in regulating plasma lipid metabolic disorder,enhancing anti-oxidant capacity and so on.(1) SX has obvious effect on decreasing the serum levels of MDA and increasing the serum levels of SOD in AS rats.(2)SX has obvious effect on decreasing the serum levels of Hcy.(3) SX has obvious effect on decreasing the serum levels of ADMA.We also found that the level of Hcy is correlated with the level of ADMA from our experiment.
方法:采用高脂饮食加大剂量钙负荷(一次性腹腔注射维生素D_360万U/kg)方法建立大鼠AS模型。选用健康雄性成年Sprague-Dawlay(SD)大鼠50只,随即分为5组:①正常对照组(N):普通饲料;②模型组(M):高脂饲料;③速效救心丸低剂量治疗组(SXL):高脂饲料+SX60mg·kg~(-1)·d~(-1);④速效救心丸中剂量治疗组(SXM):高脂饲料+SX600mg·kg~(-1)·d~(-1);⑤速效救心丸高剂量治疗组(SXH):高脂饲料+SX1800mg·kg~(-1)·d~(-1);各治疗组药物自造模第一天开始灌胃给予,正常对照组和模型组给予等量生理盐水灌胃,共饲养12周。生化方法测定血清中丙二醛(malondialdehyde,MDA)的含量及超氧化物歧化酶(superoxidedismutase,SOD)的活性;高效液相色谱法加荧光测定同型半胱氨酸(homocysteine,Hcy)及不对称二甲基精氨酸(asymmetric dimethylarginine,ADMA)含量
结果:
1.超氧化物歧化酶、丙二醛:模型组大鼠血清中SOD活性明显低于正常组,差异有统计学意义(P＜0.05),MDA含量显著高于正常组(P＜0.05),速效救心丸预防组中低剂量组对SOD活性、MDA含量影响不明显,差别没有统计学意义(P＞0.05):中、高剂量组能升高SOD活性、降低MDA含量,与模型组相比,差别有统计学意义(P＜0.05)。
2.同型半胱氨酸:模型组大鼠血清Hcy含量高于对照组,两者差异有统计学意义(p＜0.05),速效救心丸低剂量组血清Hcy含量比模型组低,但差异没有统计学意义(p＞0.05),速效救心丸中、高剂量及均能明显降低各组大鼠血清中Hcy含量,各组与模型组相比,差异均有统计学意义(p＜0.05)。
3.不对称二甲基精氨酸:模型组大鼠血清ADMA含量高于对照组,两者差异有统计学意义(p＜0.05),速效救心丸低剂量组血清ADMA含量比模型组低,差异有统计学意义(p＜0.05),速效救心丸中、高剂量均能明显降低各组大鼠血清中ADMA含量,各组与模型组相比,差异均有统计学意义(p＜0.05)。
结论:高脂饮食加一次性大??维生素D_3负荷共同作用可成功建立大鼠早期AS模型。速效救心丸具有降血脂、抗脂质过氧化等抑制AS的形成的作用,其可能的机制是:(1)速效救心丸可降低AS大鼠血清MDA,升高SOD水平;(2)速效救心丸可以降低血清中Hcy水平;(3)速效救心丸可以降低血清中ADMA水平。本试验还证实动脉粥样硬化时同型半胱氨酸和不对称二甲基精氨酸确实存在正相关,为进一步探索动脉粥样硬化发病机制提供了理论依据。
Objective:To investigate the anti-atherosclerosis effects of SuXiao JiuXin Wan and its possible mechanism through animal model of experimental atherosclerosis.
Method:Experimental atherosclerosis in rats was produced by feeding with atherogenic-diet and vitamin D_3 administration(600,000 IU/kg by intraperitoneal injected at one time) for 12 weeks.50 male mature Sprague-Dawlay rats were divided into 5 groups randomly and equally:1.normal group(normal diet);2.AS model group (atherogenic-diet);3.SXL group(atherogenic-diet and SX 60mg·kg~(-1)·d~(-1));4.SXM group(atherogenic-diet and SX 600mg·kg~(-1)·d~(-1));5.SXH group(atherogenic-diet and SX 1800mg·kg~(-1)·d~(-1));SX was given by gavage from the beginning of the first week to the end of the experiment.At the same time,normal saline was given to the rats of normal group and model group with the same volume and the same way.After 12 weeks treatment,all rats were killed.Blood was collected to detect the levels of serum levels of malondialdehyde(MDA) and superoxide dismutase(SOD) by biochemistry method.The serum levels of homocysteine(Hcy) and asymmetric dimethylarginine(ADMA) were mearsured by high-performance liquid chromatography(HPLC) method.
Results:
1.In the model group,the serum SOD activity was declined and the MDA level was increased compared with the normal group(P＜0.05).Compared with the model group,the serum SOD and MDA level did not change appreciably in the SXL group(P＞0.05),while the serum SOD activity was increased and the MDA level was decreased definitely in the SXM,SXH groups(P＜0.05).
2.In the model group,the serum Hcy level was increased compared with the normal group(P＜0.05).Compared with the model group,the serum Hey level did not change appreciably in the SXL group(P＞0.05),while the serum Hcy level was decreased definitely in the SXM、SXH groups(P＜0.05).
3.In the model group,the serum ADMA level was increased compared with the normal group(P＜0.05).Compared with the model group,the serum ADMA level was changed appreciably in the SXL group(P＜0.05),and the serum ADMA level was decreased definitely in the SXM、SXH groups(P＜0.05).
Conclusions:The rat model of early atherosclerosis can be established successfully by atherogenic-diet and vitaminD3 administration(600,000 IU/kg by intraperitoneal injected at one time).The results suggest that the SuXiao JiuXin Wan can ameliorate the atherosclerotic changes and its protection effect may be involve in regulating plasma lipid metabolic disorder,enhancing anti-oxidant capacity and so on.(1) SX has obvious effect on decreasing the serum levels of MDA and increasing the serum levels of SOD in AS rats.(2)SX has obvious effect on decreasing the serum levels of Hcy.(3) SX has obvious effect on decreasing the serum levels of ADMA.We also found that the level of Hcy is correlated with the level of ADMA from our experiment.
引文
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