加味青麟丸对高脂血症小鼠调脂作用及其机制的研究
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摘要
目的:加味青麟丸由酒制大黄、党参、制首乌组成,具有益气化瘀降浊的功效,为导师杨继军教授多年临床观察筛选研制的效方,对高脂血症具有较好的治疗效果,为进一步验证加味青麟丸的药效并说明其作用机制,本研究采用高脂饲料复制高脂血症动物模型,同时施加药物干预,旨在通过观察对总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)的影响,探讨其调节脂质代谢的作用;通过观察对丙二醛(MDA)、超氧化物歧化酶(SOD)的影响,探讨其抗脂质过氧化损伤的作用机制;通过观察对内皮素-1(ET-1)、降钙素基因相关肽(CGRP)、血栓素B2(TXB_2)、6-酮-前列环素F_(1α)(6-Keto-PGF_(1α))的影响,探讨其对血管舒缩状态和血液运行等方面的作用机制。
方法:
第一部分加味青麟丸对高脂血症小鼠脂代谢的影响
选用健康雄性昆明小鼠50只,随机分为5组:⑴正常对照组(简称正常组);⑵模型对照组(简称模型组);⑶加味青麟丸低剂量组(简称低剂量组);⑷加味青麟丸高剂量组(简称高剂量组);⑸辛伐他汀对照组(简称辛伐他汀组)。除正常组喂饲普通饲料外,其余各组均喂饲高脂饲料。同时,给药组每日分别灌胃加味青麟丸低剂量1.5g/Kg,高剂量3.0g/Kg,辛伐他汀6.6mg/Kg,正常组和模型组每日给予同体积蒸馏水。每次用药体积均按0.2ml/10g计算,各组灌胃1次/天,连续灌胃4周。末次给药禁食不禁水12h后各组小鼠摘除眼球取血,将血样低温离心,分离血清,密封,-20℃冷存待检。血清TC、TG、HDL-C、LDL-C的含量测定均采用生化法,测定步骤和计算公式均严格按照试剂盒说明书操作。
第二部分加味青麟丸对高脂血症小鼠血清MDA含量、SOD活力的影响
实验动物分组、造模及给药方法同前。连续灌胃4周,于末次给药禁食不禁水12h后各组小鼠摘除眼球取血,将血样低温离心,分离血清,密封,-20℃冷存待检。血清MDA测定采用硫代巴比妥酸(TBA)比色分析法,SOD活力测定采用黄嘌呤氧化酶法,测定步骤和计算公式均严格按照试剂盒说明书操作。
第三部分加味青麟丸对高脂血症小鼠血浆ET-1、CGRP及TXB_2、6-Keto-PGF_(1α)含量的影响
实验动物分组、造模及给药方法同前。连续灌胃4周,于末次给药禁食不禁水12h后各组小鼠摘除眼球取血,将血样分成两份,分别装入加有不同抗凝剂的试管中混匀,低温离心,分离血浆,密封,-80℃冷存待检。ET-1、CGRP、TXB_2和6-Keto-PGF_(1α)均采用放射免疫法,测定步骤和计算公式均严格按照试剂盒说明书操作。
结果:
第一部分加味青麟丸对高脂血症小鼠脂代谢的影响
加味青麟丸对高脂血症小鼠血清中TC、TG、HDL-C、LDL-C含量的影响
高脂血症模型组(5.06±0.90、1.98±0.41、2.31±0.39)小鼠血清TC、TG、LDL-C含量均明显高于正常组(3.71±0.30、0.89±0.27、1.57±0.18)(P<0.01),模型组(1.43±0.18)血清HDL-C含量明显低于正常组(1.81±0.14)(P<0.01);药物干预各组TC、TG、LDL-C含量均明显低于模型组,HDL-C含量明显高于模型组(P<0.05或P<0.01);高剂量组(3.95±0.41、1.78±0.12、1.69±0.14),低剂量组(3.93±0.30、1.79±0.13、1.67±0.15)和辛伐他汀组(4.02±0.33、1.82±0.14、1.66±0.10)之间血清TC、LDL-C和HDL-C的含量无显著性差异(P>0.05),而高剂量组(1.28±0.19)和低剂量组(1.26±0.45)血清TG的含量均低于辛伐他汀组(1.61±0.16)(P<0.05),高、低剂量组之间TG的含量无显著性差异(P>0.05)。
第二部分加味青麟丸对高脂血症小鼠血清MDA含量、SOD活力的影响
1加味青麟丸对高脂血症小鼠血清MDA含量的影响
高脂血症模型组(20.94±3.49)小鼠血清MDA含量明显高于正常组(11.94±1.44)(P<0.01);药物干预各组血清MDA含量均明显低于模型组(P<0.01);其中高剂量组(13.77±1.41)和低剂量组(15.87±1.51)均低于辛伐他汀组(17.95±1.24)(P<0.05或P<0.01),而高剂量组低于低剂量组(P<0.05)。
2加味青麟丸对高脂血症小鼠血清SOD活力的影响
高脂血症模型组(160.6±10.64)小鼠血清SOD活力明显低于正常组(236.2±12.89)(P<0.01);药物干预各组血清SOD活力均明显高于模型组(P<0.01);其中高剂量组(205.7±11.82)和低剂量组(193.0±11.55)均高于辛伐他汀组(181.9±11.40)(P<0.05或P<0.01),而高剂量组高于低剂量组(P<0.05)。
第三部分加味青麟丸对高脂血症小鼠血浆ET-1、CGRP及TXB_2、6-Keto-PGF_(1α)含量的影响
1加味青麟丸对高脂血症小鼠血浆ET-1含量的影响
高脂血症模型组(126.95±15.46)小鼠血浆ET-1的含量明显高于正常组(67.78±7.04)(P<0.01);药物干预各组血浆ET-1的含量均明显低于模型组(P<0.01);其中高剂量组(74.29±6.65)和低剂量组(85.41±9.93)均低于辛伐他汀组(100.43±9.44)(P<0.01),而高剂量组低于低剂量组(P<0.05)。
2加味青麟丸对高脂血症小鼠血浆CGRP含量的影响
高脂血症模型组(54.83±7.18)小鼠血浆CGRP的含量明显低于正常组(105.65±11.65)(P<0.01);药物干预各组血浆CGRP的含量均明显高于模型组(P<0.01);其中高剂量组(89.63±8.18)和低剂量组(80.49±8.28)均高于辛伐他汀组(67.54±6.79)(P<0.01),而高剂量组高于低剂量组(P<0.05)。
3加味青麟丸对高脂血症小鼠血浆TXB_2含量的影响
高脂血症模型组(2704.24±370.59)小鼠血浆TXB_2的含量明显高于正常组(1514.64±342.93)(P<0.01);药物干预各组血浆TXB_2的含量均明显低于模型组(P<0.05或P<0.01 );其中高剂量组( 1883.46±332.30 )和低剂量组(1893.38±237.39)均低于辛伐他汀组(2294.48±340.49)(P<0.05),而高、低剂量组之间无显著性差异(P>0.05)。
4加味青麟丸对高脂血症小鼠血浆6-Keto-PGF_(1α)含量的影响
高脂血症模型组(924.37±153.28)小鼠血浆6-Keto-PGF_(1α)的含量明显低于正常组(1370.19±131.21)(P<0.01);药物干预各组血浆6-Keto-PGF_(1α)均明显高于模型组(P<0.05或P<0.01);其中高剂量组(1236.70±144.09)和低剂量组(1245.92±157.26)均高于辛伐他汀组(1093.73±135.86)(P<0.05),而高、低剂量组之间无显著性差异(P>0.05)。
5加味青麟丸对高脂血症小鼠血浆TXB_2/6-Keto-PGF_(1α)的影响
高脂血症模型组(2.98±0.52)小鼠血浆TXB_2 / 6-Keto-PGF_(1α)明显高于正常组(1.10±0.23)(P<0.01);用药干预各组血浆TXB_2/6-Keto-PGF_(1α)均明显低于模型组(P<0.01);其中高剂量组(1.53±0.31)和低剂量组(1.47±0.24)血浆TXB_2/6-Keto-PGF_(1α)均低于辛伐他汀组(2.12±0.40)(P<0.01),而高、低剂量组之间无显著性差异(P>0.05)。
结论:
1加味青麟丸可降低高脂血症模型小鼠血清TC、TG、LDL-C含量,升高HDL-C含量,具有较好的调节脂质代谢的作用。
2该方可降低高脂血症模型小鼠血清MDA含量,提高SOD活力,抑制机体脂质过氧化反应,增加抗氧化能力,通过改善自由基代谢,以减轻高脂血症引发的氧化损伤。
3该方可降低高脂血症模型小鼠血浆ET-1、TXB_2含量,升高CGRP、6-Keto-PGF_(1α)含量,降低TXB_2/6-Keto-PGF_(1α),通过调节血管平滑肌收缩与舒张,抑制血小板聚集和血栓形成,以维持血管张力及血流畅通,减轻高脂血症引发的血管内皮损伤,从而保护血管内皮功能。
Objective: Added Herbs’QingLin Pill (composed of jiuzhidahuang, dangshen, zhishouwu) has the function of benefiting vital energy, removing stasis and phlegm and is an effective formula through years of clinical observation by Professor YANG Ji-jun. And it has been proved significantly effect in treating hyperlipemia. In order to further probe its action mechanism, we duplicated the hyperlipemia animal model with high-fat forage, At the same time, we interfered the animal with medicine. And we studied the action mechanism of this formula in regulating lipid metabolism through observing its effect on TC,TG,HDL-C,LDL-C; We also studied its action mechanism in resisting lipid peroxidation injury through observing its effect on MDA,SOD; We studied the action mechanism of this formula in vasomotion state and blood flow through observing its effect on ET-1,CGRP,TXB_2 and 6-Keto-PGF_(1α).
Methods:
PartⅠEffect of Added Herbs’QingLin Pill on lipid metabolism of hyperlipemia mice
50 healthy male KM mice were divided into 5 groups at random, namely, (1) Normal control group(normal group for short); (2) Model control group(model group for short); (3) Low-dose group of Added Herbs’Qing-Lin Pill group(low-dose group for short); (4) High-dose group of Added Herbs’Qing-Lin Pill group (high-dose group); (5) Simvastatin control group (simvastatin group for short). Except for normal group was fed with ordinary forage, the rest of groups were all fed with high-fat forage. At the same time, the treatment groups were given low-dose of Added Herbs’Qing-Lin Pill 1.5 g /Kg, high-dose of Added Herbs’Qing-Lin Pill 3.0 g /Kg and Simvastatin 6.6 mg /Kg per day. Normal and model group were given distilled water. Mice in each group were given stomach-perfusion once a day and every time the drug volume was calculated by 0.2 ml/10g. Stomach-perfusion lasted for 4 weeks. Then 12 hours after fasting and not prohibiting water of the last time, the mice were removed eyeball and their blood were drawn out, the blood sample was made centrifugation with low temperature and the blood serum was isolated. It was sealed up and keep temperature of under -20℃to examine them later. Finally the contents of TC,TG,HDL-C,LDL-C were measured with biochemistry method. The contents of each item were measured strictly according to the directions of reagent box.
PartⅡEffect of Added Herbs’QingLin Pill on the content of MDA and the activity of SOD in serum of hyperlipemia mice
The group distribution, duplication of the hyperlipemia animal model and drug-given were exactly same as above. After 4 weeks continuous stomach-perfusion, then 12 hours after fasting and not prohibiting water of the last time, the mice were removed eyeball and their blood were drawn out. The blood sample was made centrifugation with low temperature and the blood serum was isolated. It was sealed up and keep temperature of under -20℃to examine them later. The content of MDA was examined by the method of TBA colorimeter analysis and activity of SOD was examined by the method of xanthine oxidase. The content of each item was measured strictly according to the directions of reagent box.
PartⅢEffect of Added Herbs’QingLin Pill on the contents of ET-1, CGRP, TXB_2 and 6-Keto-PGF_(1α) in blood plasma of hyperlipemia mice
The group distribution, duplication of the hyperlipemia animal model and drug-given are exactly same as above. After 4 weeks continuous stomach-perfusion, then 12 hours after fasting of the last time, the mice were removed eyeball and their blood were drawn out. The blood sample was divided two portions and builded in sample tubes of containing different decoagulant and misced bene. The blood sample was made centrifugation with low temperature and the plasma was isolated. It was sealed up and keep temperature of under -80℃to examine them later.Finally the contents of ET-1, CGRP, TXB_2 and 6-Keto-PGF_(1α) were all measured with radio-immuno method. The content of each item was measured strictly according to the directions of reagent box.
Results:
PartⅠEffect of Added Herbs’QingLin Pill on lipid metabolism of hyperlipemia mice
Effect of Added Herbs’QingLin Pill on the contents of TC, TG, HDL-C and LDL-C in serum of hyperlipemia mice
The contents of TC, TG, LDL-C in serum of model group (5.06±0.90, 1.98±0.41, 2.31±0.39) were all higher than normal group (3.71±0.30, 0.89±0.27, 1.57±0.18) (P < 0.01), while HDL-C of model group (1.43±0.18) was lower than normal group (1.81±0.14) (P<0.01); After the intervention of medicine, the contents of TC, TG, LDL-C in serum of each treatment group were all lower than the model group, while HDL-C was higher than the model group (P<0.05 or P<0.01); The contents of TC, LDL-C and HDL-C in serum were no significant difference in high-dose group (3.95±0.41, 1.78±0.12, 1.69±0.14), low-dose group (3.93±0.30, 1.79±0.13, 1.67±0.15) and simvastatin group (4.02±0.33, 1.82±0.14, 1.66±0.10) (P>0.05). But the contents of TG in low-dose group (1.26±0.45) and high-dose group (1.28±0.19) were lower than simvastatin group (1.61±0.16) (P<0.05). And there was no significant difference between low-dose and high-dose group (P>0.05).
PartⅡEffect of Added Herbs’QingLin Pill on the content of MDA and the activity of SOD in serum of hyperlipemia mice
1 Effect of Added Herbs’QingLin Pill on the content of MDA in serum of hyperlipemia mice
The content of MDA in serum of model group (20.94±3.49) was higher than the normal group (11.94±1.44) (P<0.01); After the intervention of medicine, the content of MDA in serum of each treatment group was lower than the model group (P<0.01); But the contents of MDA in low-dose group (15.87±1.51) and high-dose group (13.77±1.41) were lower than simvastatin group (17.95±1.24) (P<0.05 or P<0.01). The high-dose group was lower than the low-dose group (P<0.05).
2 Effect of Added Herbs’QingLin Pill on the activity of SOD in serum of hyperlipemia mice
The activity of SOD in serum of model group (160.6±10.64) was lower than the normal group (236.2±12.89) (P<0.01); After the intervention of medicine, the activity of SOD in serum of each treatment group was higher than the model group (P<0.01); But the activity of SOD in low-dose group (193.0±11.55) and high-dose group (205.7±11.82) were higher than simvastatin group (181.9±11.40) (P<0.05 or P<0.01). The high-dose group was higher than the low-dose group (P<0.05).
PartⅢEffect of Added Herbs’QingLin Pill on the contents of ET-1, CGRP,TXB_2 and 6-Keto-PGF_(1α) in blood plasma of hyperlipemia mice
1 Effect of Added Herbs’QingLin Pill on the content of ET-1 in plasma of hyperlipemia mice
The content of ET-1 in plasma of model group (126.95±15.46) was higher than the normal group (67.78±7.04) (P<0.01); After the intervention of medicine, the content of ET-1 in plasma of each treatment group was lower than the model group (P<0.01); But the contents of ET-1 in low-dose group (85.41±9.93) and high-dose group (74.29±6.65) were lower than simvastatin group (100.43±9.44) (P<0.01). The high-dose group was lower than the low-dose group (P<0.05).
2 Effect of Added Herbs’QingLin Pill on the content of CGRP in plasma of hyperlipemia mice
The content of CGRP in plasma of model group (54.83±7.18) was lower than the normal group (105.65±11.65) (P<0.01); After the intervention of medicine, the content of CGRP in plasma of each treatment group was higher than the model group (P<0.01); But the contents of CGRP in low-dose group (80.49±8.28) and high-dose group (89.63±8.18) were higher than simvastatin group (67.54±6.79) (P<0.01). The high-dose group was higher than the low-dose group (P<0.05).
3 Effect of Added Herbs’QingLin Pill on the content of TXB_2 in plasma of hyperlipemia mice
The content of TXB_2 in plasma of model group (2704.24±370.59) was higher than the normal group (1514.64±342.93) (P<0.01); After the intervention of medicine, the content of TXB_2 in plasma of each treatment group was lower than the model group (P<0.05 or P<0.01); But the contents of TXB_2 in low-dose group (1893.38±237.39) and high-dose group (1883.46±332.30) were lower than simvastatin group (2294.48±340.49) (P<0.05). And there was no significant difference between low-dose and high-dose group(P>0.05).
4 Effect of Added Herbs’QingLin Pill on the content of 6-Keto-PGF_(1α) in plasma of hyperlipemia mice
The content of 6-Keto-PGF_(1α) in plasma of model group (924.37±153.28) was lower than the normal group (1370.19±131.21) (P<0.01); After the intervention of medicine, the content of 6-Keto-PGF_(1α) in plasma of each treatment group was higher than the model group (P<0.05 or P<0.01); But the contents of 6-Keto-PGF_(1α) in low-dose group (1245.92±157.26) and high-dose group (1236.70±144.09) were higher than simvastatin group (1093.73±135.86) (P<0.05). And there was no significant difference between low-dose and high-dose group (P>0.05).
5 Effect of Added Herbs’QingLin Pill on TXB_2/ 6-Keto -PGF_(1α) in plasma of hyperlipemia mice
The TXB_2/6-Keto-PGF_(1α) in plasma of model group (2.98±0.52) was higher than the normal group (1.10±0.23) (P<0.01); After the intervention of medicine, the TXB_2/6-Keto-PGF_(1α) in plasma of each treatment group was lower than the model group (P<0.01); But the TXB_2/6-Keto-PGF_(1α) in low-dose group (1.47±0.24) and high-dose group (1.53±0.31) were lower than simvastatin group (2.12±0.40) (P<0.05). And there was no significant difference between low-dose and high-dose group (P>0.05).
Conclusion:
1 Added Herbs’QingLin Pill has decreased the contents of TC,TG,LDL-C and increased the content of HDL-C in serum. The result shows that it has marked function of regulating lipid metabolism.
2 It obviously increased the activity of SOD, and decreased the content of MDA in serum. The result shows that it has marked function of inhibiting lipid peroxidation reaction and raising anti-oxidative ability. It could reduce oxidative damage of hyperlipemia through amending free radical metabolism.
3 It obviously decreased the contents of ET-1 with TXB_2 and increases the contents of CGRP with 6-Keto-PGF_(1α) in plasma. And it obviously regulated the proportion of TXB_2 and 6-Keto-PGF_(1α) in plasma. The results shows that it has marked function of regulating the normal contraction and dilation state of vascular smooth muscle , which in order to remove the platelet coagulation with thrombosis. It could prevent the blood vessel endothelium damage of hyperlipemia and protect blood vessel endothelium function.
方法:
第一部分加味青麟丸对高脂血症小鼠脂代谢的影响
选用健康雄性昆明小鼠50只,随机分为5组:⑴正常对照组(简称正常组);⑵模型对照组(简称模型组);⑶加味青麟丸低剂量组(简称低剂量组);⑷加味青麟丸高剂量组(简称高剂量组);⑸辛伐他汀对照组(简称辛伐他汀组)。除正常组喂饲普通饲料外,其余各组均喂饲高脂饲料。同时,给药组每日分别灌胃加味青麟丸低剂量1.5g/Kg,高剂量3.0g/Kg,辛伐他汀6.6mg/Kg,正常组和模型组每日给予同体积蒸馏水。每次用药体积均按0.2ml/10g计算,各组灌胃1次/天,连续灌胃4周。末次给药禁食不禁水12h后各组小鼠摘除眼球取血,将血样低温离心,分离血清,密封,-20℃冷存待检。血清TC、TG、HDL-C、LDL-C的含量测定均采用生化法,测定步骤和计算公式均严格按照试剂盒说明书操作。
第二部分加味青麟丸对高脂血症小鼠血清MDA含量、SOD活力的影响
实验动物分组、造模及给药方法同前。连续灌胃4周,于末次给药禁食不禁水12h后各组小鼠摘除眼球取血,将血样低温离心,分离血清,密封,-20℃冷存待检。血清MDA测定采用硫代巴比妥酸(TBA)比色分析法,SOD活力测定采用黄嘌呤氧化酶法,测定步骤和计算公式均严格按照试剂盒说明书操作。
第三部分加味青麟丸对高脂血症小鼠血浆ET-1、CGRP及TXB_2、6-Keto-PGF_(1α)含量的影响
实验动物分组、造模及给药方法同前。连续灌胃4周,于末次给药禁食不禁水12h后各组小鼠摘除眼球取血,将血样分成两份,分别装入加有不同抗凝剂的试管中混匀,低温离心,分离血浆,密封,-80℃冷存待检。ET-1、CGRP、TXB_2和6-Keto-PGF_(1α)均采用放射免疫法,测定步骤和计算公式均严格按照试剂盒说明书操作。
结果:
第一部分加味青麟丸对高脂血症小鼠脂代谢的影响
加味青麟丸对高脂血症小鼠血清中TC、TG、HDL-C、LDL-C含量的影响
高脂血症模型组(5.06±0.90、1.98±0.41、2.31±0.39)小鼠血清TC、TG、LDL-C含量均明显高于正常组(3.71±0.30、0.89±0.27、1.57±0.18)(P<0.01),模型组(1.43±0.18)血清HDL-C含量明显低于正常组(1.81±0.14)(P<0.01);药物干预各组TC、TG、LDL-C含量均明显低于模型组,HDL-C含量明显高于模型组(P<0.05或P<0.01);高剂量组(3.95±0.41、1.78±0.12、1.69±0.14),低剂量组(3.93±0.30、1.79±0.13、1.67±0.15)和辛伐他汀组(4.02±0.33、1.82±0.14、1.66±0.10)之间血清TC、LDL-C和HDL-C的含量无显著性差异(P>0.05),而高剂量组(1.28±0.19)和低剂量组(1.26±0.45)血清TG的含量均低于辛伐他汀组(1.61±0.16)(P<0.05),高、低剂量组之间TG的含量无显著性差异(P>0.05)。
第二部分加味青麟丸对高脂血症小鼠血清MDA含量、SOD活力的影响
1加味青麟丸对高脂血症小鼠血清MDA含量的影响
高脂血症模型组(20.94±3.49)小鼠血清MDA含量明显高于正常组(11.94±1.44)(P<0.01);药物干预各组血清MDA含量均明显低于模型组(P<0.01);其中高剂量组(13.77±1.41)和低剂量组(15.87±1.51)均低于辛伐他汀组(17.95±1.24)(P<0.05或P<0.01),而高剂量组低于低剂量组(P<0.05)。
2加味青麟丸对高脂血症小鼠血清SOD活力的影响
高脂血症模型组(160.6±10.64)小鼠血清SOD活力明显低于正常组(236.2±12.89)(P<0.01);药物干预各组血清SOD活力均明显高于模型组(P<0.01);其中高剂量组(205.7±11.82)和低剂量组(193.0±11.55)均高于辛伐他汀组(181.9±11.40)(P<0.05或P<0.01),而高剂量组高于低剂量组(P<0.05)。
第三部分加味青麟丸对高脂血症小鼠血浆ET-1、CGRP及TXB_2、6-Keto-PGF_(1α)含量的影响
1加味青麟丸对高脂血症小鼠血浆ET-1含量的影响
高脂血症模型组(126.95±15.46)小鼠血浆ET-1的含量明显高于正常组(67.78±7.04)(P<0.01);药物干预各组血浆ET-1的含量均明显低于模型组(P<0.01);其中高剂量组(74.29±6.65)和低剂量组(85.41±9.93)均低于辛伐他汀组(100.43±9.44)(P<0.01),而高剂量组低于低剂量组(P<0.05)。
2加味青麟丸对高脂血症小鼠血浆CGRP含量的影响
高脂血症模型组(54.83±7.18)小鼠血浆CGRP的含量明显低于正常组(105.65±11.65)(P<0.01);药物干预各组血浆CGRP的含量均明显高于模型组(P<0.01);其中高剂量组(89.63±8.18)和低剂量组(80.49±8.28)均高于辛伐他汀组(67.54±6.79)(P<0.01),而高剂量组高于低剂量组(P<0.05)。
3加味青麟丸对高脂血症小鼠血浆TXB_2含量的影响
高脂血症模型组(2704.24±370.59)小鼠血浆TXB_2的含量明显高于正常组(1514.64±342.93)(P<0.01);药物干预各组血浆TXB_2的含量均明显低于模型组(P<0.05或P<0.01 );其中高剂量组( 1883.46±332.30 )和低剂量组(1893.38±237.39)均低于辛伐他汀组(2294.48±340.49)(P<0.05),而高、低剂量组之间无显著性差异(P>0.05)。
4加味青麟丸对高脂血症小鼠血浆6-Keto-PGF_(1α)含量的影响
高脂血症模型组(924.37±153.28)小鼠血浆6-Keto-PGF_(1α)的含量明显低于正常组(1370.19±131.21)(P<0.01);药物干预各组血浆6-Keto-PGF_(1α)均明显高于模型组(P<0.05或P<0.01);其中高剂量组(1236.70±144.09)和低剂量组(1245.92±157.26)均高于辛伐他汀组(1093.73±135.86)(P<0.05),而高、低剂量组之间无显著性差异(P>0.05)。
5加味青麟丸对高脂血症小鼠血浆TXB_2/6-Keto-PGF_(1α)的影响
高脂血症模型组(2.98±0.52)小鼠血浆TXB_2 / 6-Keto-PGF_(1α)明显高于正常组(1.10±0.23)(P<0.01);用药干预各组血浆TXB_2/6-Keto-PGF_(1α)均明显低于模型组(P<0.01);其中高剂量组(1.53±0.31)和低剂量组(1.47±0.24)血浆TXB_2/6-Keto-PGF_(1α)均低于辛伐他汀组(2.12±0.40)(P<0.01),而高、低剂量组之间无显著性差异(P>0.05)。
结论:
1加味青麟丸可降低高脂血症模型小鼠血清TC、TG、LDL-C含量,升高HDL-C含量,具有较好的调节脂质代谢的作用。
2该方可降低高脂血症模型小鼠血清MDA含量,提高SOD活力,抑制机体脂质过氧化反应,增加抗氧化能力,通过改善自由基代谢,以减轻高脂血症引发的氧化损伤。
3该方可降低高脂血症模型小鼠血浆ET-1、TXB_2含量,升高CGRP、6-Keto-PGF_(1α)含量,降低TXB_2/6-Keto-PGF_(1α),通过调节血管平滑肌收缩与舒张,抑制血小板聚集和血栓形成,以维持血管张力及血流畅通,减轻高脂血症引发的血管内皮损伤,从而保护血管内皮功能。
Objective: Added Herbs’QingLin Pill (composed of jiuzhidahuang, dangshen, zhishouwu) has the function of benefiting vital energy, removing stasis and phlegm and is an effective formula through years of clinical observation by Professor YANG Ji-jun. And it has been proved significantly effect in treating hyperlipemia. In order to further probe its action mechanism, we duplicated the hyperlipemia animal model with high-fat forage, At the same time, we interfered the animal with medicine. And we studied the action mechanism of this formula in regulating lipid metabolism through observing its effect on TC,TG,HDL-C,LDL-C; We also studied its action mechanism in resisting lipid peroxidation injury through observing its effect on MDA,SOD; We studied the action mechanism of this formula in vasomotion state and blood flow through observing its effect on ET-1,CGRP,TXB_2 and 6-Keto-PGF_(1α).
Methods:
PartⅠEffect of Added Herbs’QingLin Pill on lipid metabolism of hyperlipemia mice
50 healthy male KM mice were divided into 5 groups at random, namely, (1) Normal control group(normal group for short); (2) Model control group(model group for short); (3) Low-dose group of Added Herbs’Qing-Lin Pill group(low-dose group for short); (4) High-dose group of Added Herbs’Qing-Lin Pill group (high-dose group); (5) Simvastatin control group (simvastatin group for short). Except for normal group was fed with ordinary forage, the rest of groups were all fed with high-fat forage. At the same time, the treatment groups were given low-dose of Added Herbs’Qing-Lin Pill 1.5 g /Kg, high-dose of Added Herbs’Qing-Lin Pill 3.0 g /Kg and Simvastatin 6.6 mg /Kg per day. Normal and model group were given distilled water. Mice in each group were given stomach-perfusion once a day and every time the drug volume was calculated by 0.2 ml/10g. Stomach-perfusion lasted for 4 weeks. Then 12 hours after fasting and not prohibiting water of the last time, the mice were removed eyeball and their blood were drawn out, the blood sample was made centrifugation with low temperature and the blood serum was isolated. It was sealed up and keep temperature of under -20℃to examine them later. Finally the contents of TC,TG,HDL-C,LDL-C were measured with biochemistry method. The contents of each item were measured strictly according to the directions of reagent box.
PartⅡEffect of Added Herbs’QingLin Pill on the content of MDA and the activity of SOD in serum of hyperlipemia mice
The group distribution, duplication of the hyperlipemia animal model and drug-given were exactly same as above. After 4 weeks continuous stomach-perfusion, then 12 hours after fasting and not prohibiting water of the last time, the mice were removed eyeball and their blood were drawn out. The blood sample was made centrifugation with low temperature and the blood serum was isolated. It was sealed up and keep temperature of under -20℃to examine them later. The content of MDA was examined by the method of TBA colorimeter analysis and activity of SOD was examined by the method of xanthine oxidase. The content of each item was measured strictly according to the directions of reagent box.
PartⅢEffect of Added Herbs’QingLin Pill on the contents of ET-1, CGRP, TXB_2 and 6-Keto-PGF_(1α) in blood plasma of hyperlipemia mice
The group distribution, duplication of the hyperlipemia animal model and drug-given are exactly same as above. After 4 weeks continuous stomach-perfusion, then 12 hours after fasting of the last time, the mice were removed eyeball and their blood were drawn out. The blood sample was divided two portions and builded in sample tubes of containing different decoagulant and misced bene. The blood sample was made centrifugation with low temperature and the plasma was isolated. It was sealed up and keep temperature of under -80℃to examine them later.Finally the contents of ET-1, CGRP, TXB_2 and 6-Keto-PGF_(1α) were all measured with radio-immuno method. The content of each item was measured strictly according to the directions of reagent box.
Results:
PartⅠEffect of Added Herbs’QingLin Pill on lipid metabolism of hyperlipemia mice
Effect of Added Herbs’QingLin Pill on the contents of TC, TG, HDL-C and LDL-C in serum of hyperlipemia mice
The contents of TC, TG, LDL-C in serum of model group (5.06±0.90, 1.98±0.41, 2.31±0.39) were all higher than normal group (3.71±0.30, 0.89±0.27, 1.57±0.18) (P < 0.01), while HDL-C of model group (1.43±0.18) was lower than normal group (1.81±0.14) (P<0.01); After the intervention of medicine, the contents of TC, TG, LDL-C in serum of each treatment group were all lower than the model group, while HDL-C was higher than the model group (P<0.05 or P<0.01); The contents of TC, LDL-C and HDL-C in serum were no significant difference in high-dose group (3.95±0.41, 1.78±0.12, 1.69±0.14), low-dose group (3.93±0.30, 1.79±0.13, 1.67±0.15) and simvastatin group (4.02±0.33, 1.82±0.14, 1.66±0.10) (P>0.05). But the contents of TG in low-dose group (1.26±0.45) and high-dose group (1.28±0.19) were lower than simvastatin group (1.61±0.16) (P<0.05). And there was no significant difference between low-dose and high-dose group (P>0.05).
PartⅡEffect of Added Herbs’QingLin Pill on the content of MDA and the activity of SOD in serum of hyperlipemia mice
1 Effect of Added Herbs’QingLin Pill on the content of MDA in serum of hyperlipemia mice
The content of MDA in serum of model group (20.94±3.49) was higher than the normal group (11.94±1.44) (P<0.01); After the intervention of medicine, the content of MDA in serum of each treatment group was lower than the model group (P<0.01); But the contents of MDA in low-dose group (15.87±1.51) and high-dose group (13.77±1.41) were lower than simvastatin group (17.95±1.24) (P<0.05 or P<0.01). The high-dose group was lower than the low-dose group (P<0.05).
2 Effect of Added Herbs’QingLin Pill on the activity of SOD in serum of hyperlipemia mice
The activity of SOD in serum of model group (160.6±10.64) was lower than the normal group (236.2±12.89) (P<0.01); After the intervention of medicine, the activity of SOD in serum of each treatment group was higher than the model group (P<0.01); But the activity of SOD in low-dose group (193.0±11.55) and high-dose group (205.7±11.82) were higher than simvastatin group (181.9±11.40) (P<0.05 or P<0.01). The high-dose group was higher than the low-dose group (P<0.05).
PartⅢEffect of Added Herbs’QingLin Pill on the contents of ET-1, CGRP,TXB_2 and 6-Keto-PGF_(1α) in blood plasma of hyperlipemia mice
1 Effect of Added Herbs’QingLin Pill on the content of ET-1 in plasma of hyperlipemia mice
The content of ET-1 in plasma of model group (126.95±15.46) was higher than the normal group (67.78±7.04) (P<0.01); After the intervention of medicine, the content of ET-1 in plasma of each treatment group was lower than the model group (P<0.01); But the contents of ET-1 in low-dose group (85.41±9.93) and high-dose group (74.29±6.65) were lower than simvastatin group (100.43±9.44) (P<0.01). The high-dose group was lower than the low-dose group (P<0.05).
2 Effect of Added Herbs’QingLin Pill on the content of CGRP in plasma of hyperlipemia mice
The content of CGRP in plasma of model group (54.83±7.18) was lower than the normal group (105.65±11.65) (P<0.01); After the intervention of medicine, the content of CGRP in plasma of each treatment group was higher than the model group (P<0.01); But the contents of CGRP in low-dose group (80.49±8.28) and high-dose group (89.63±8.18) were higher than simvastatin group (67.54±6.79) (P<0.01). The high-dose group was higher than the low-dose group (P<0.05).
3 Effect of Added Herbs’QingLin Pill on the content of TXB_2 in plasma of hyperlipemia mice
The content of TXB_2 in plasma of model group (2704.24±370.59) was higher than the normal group (1514.64±342.93) (P<0.01); After the intervention of medicine, the content of TXB_2 in plasma of each treatment group was lower than the model group (P<0.05 or P<0.01); But the contents of TXB_2 in low-dose group (1893.38±237.39) and high-dose group (1883.46±332.30) were lower than simvastatin group (2294.48±340.49) (P<0.05). And there was no significant difference between low-dose and high-dose group(P>0.05).
4 Effect of Added Herbs’QingLin Pill on the content of 6-Keto-PGF_(1α) in plasma of hyperlipemia mice
The content of 6-Keto-PGF_(1α) in plasma of model group (924.37±153.28) was lower than the normal group (1370.19±131.21) (P<0.01); After the intervention of medicine, the content of 6-Keto-PGF_(1α) in plasma of each treatment group was higher than the model group (P<0.05 or P<0.01); But the contents of 6-Keto-PGF_(1α) in low-dose group (1245.92±157.26) and high-dose group (1236.70±144.09) were higher than simvastatin group (1093.73±135.86) (P<0.05). And there was no significant difference between low-dose and high-dose group (P>0.05).
5 Effect of Added Herbs’QingLin Pill on TXB_2/ 6-Keto -PGF_(1α) in plasma of hyperlipemia mice
The TXB_2/6-Keto-PGF_(1α) in plasma of model group (2.98±0.52) was higher than the normal group (1.10±0.23) (P<0.01); After the intervention of medicine, the TXB_2/6-Keto-PGF_(1α) in plasma of each treatment group was lower than the model group (P<0.01); But the TXB_2/6-Keto-PGF_(1α) in low-dose group (1.47±0.24) and high-dose group (1.53±0.31) were lower than simvastatin group (2.12±0.40) (P<0.05). And there was no significant difference between low-dose and high-dose group (P>0.05).
Conclusion:
1 Added Herbs’QingLin Pill has decreased the contents of TC,TG,LDL-C and increased the content of HDL-C in serum. The result shows that it has marked function of regulating lipid metabolism.
2 It obviously increased the activity of SOD, and decreased the content of MDA in serum. The result shows that it has marked function of inhibiting lipid peroxidation reaction and raising anti-oxidative ability. It could reduce oxidative damage of hyperlipemia through amending free radical metabolism.
3 It obviously decreased the contents of ET-1 with TXB_2 and increases the contents of CGRP with 6-Keto-PGF_(1α) in plasma. And it obviously regulated the proportion of TXB_2 and 6-Keto-PGF_(1α) in plasma. The results shows that it has marked function of regulating the normal contraction and dilation state of vascular smooth muscle , which in order to remove the platelet coagulation with thrombosis. It could prevent the blood vessel endothelium damage of hyperlipemia and protect blood vessel endothelium function.
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3 王淑英,陈奕芝,方若鸣.石菖蒲配伍冰片对高脂血症大鼠内皮素和降钙素基因相关肽的影响.Journal Of Practical Tradtitional Chinese Medicine,2003,19(12):619~620
4 彭仁怀.中医大辞典.北京:人民卫生出版社,2000:517
5 陈奇.中药药理研究方法学.北京:人民卫生出版社,2006: 521
6 徐叔云,卞如濂,陈修.药理实验方法学.北京:人民卫生出版社,2003:1861
7 张露芬,程金莲,严洁,等.电针心经腧穴对大鼠高血脂症血浆内皮素,降钙素基因相关肽影响的实验观察.中国中医基础医学杂志,2001,7(5):60~62
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12 雷燕,黄启福,王永炎,等.中药复圣散对高脂血症大鼠脑缺血再灌注后脑内若干神经肽含量的影响.中国中西医结合杂志,2000,20(3):205~207
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14 张文姚,任爱华,于澎.康复运动对冠心病患者血流动力学和前列环素,血栓素 A2 的影响.中国临床康复,2003,7 (24):3350~3351
15 陈汉斌,许家里,江洪,等.刺五加对冠心病患者的血浆血栓素 B2 和 6-酮-前列腺素 F1α 的影响.中国煤炭工业医学杂志, 2003,11(2):172~173
16 鞠宝兆.补肾活血方调脂作用的实验研究.中国临床康复2004,8(21):4266~4267
17 常小荣,严洁,岳增辉.隔药饼灸对高脂血症兔血浆前列环素和血栓素含量的影响.中国临床康复,2004,8(33):7446~ 7447
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2 张智勇,周若梅,刘娟云,等.调脂化瘀丸治疗高脂血症 302例.陕西中医,2006,27(11):1331~1332
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12 毛大鹏,刘汝金,齐有胜.健脾利湿法法治疗高脂血症 42 例的临床观察,北京中医,2006,25(10):599~602
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16 崔春霞,崔佰宇.调理肝脾补肾法治疗老年人高脂血症 220例.河南中医学院学报,2006,21(3):51~53
17 朱立贤,金征宇.白藜芦醇苷对高脂血症大鼠血脂代谢的影响及其抗氧化作用.中成药,2006,28(2):260~261
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19 刘海燕,石元刚.葛根素对高脂血症大鼠脂质代谢及血浆PGI2, TXA2 水平的影响.第三军医大学学报,2004,26(11): 967~969
20 张露芬,程金莲,严洁,等.电针心经腧穴对大鼠高血脂症血浆内皮素,降钙素基因相关肽影响的实验观察.中国中医基础医学杂志,2001,7(5):60~62
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1 刘青云,余中敏,吴兆斌,等.调脂新对高脂血症大鼠一氧化氮内皮素,6-Keto-PGF1α/TXB2 及血液流变学的影响.中成药, 2001,23(3):196~199
2 刘海燕,石元刚.葛根素对高脂血症大鼠脂质代谢及血浆PGI2,TXA2 水平的影响.第三军医大学学报,2004,26(11): 967~969
3 王淑英,陈奕芝,方若鸣.石菖蒲配伍冰片对高脂血症大鼠内皮素和降钙素基因相关肽的影响.Journal Of Practical Tradtitional Chinese Medicine,2003,19(12):619~620
4 彭仁怀.中医大辞典.北京:人民卫生出版社,2000:517
5 陈奇.中药药理研究方法学.北京:人民卫生出版社,2006: 521
6 徐叔云,卞如濂,陈修.药理实验方法学.北京:人民卫生出版社,2003:1861
7 张露芬,程金莲,严洁,等.电针心经腧穴对大鼠高血脂症血浆内皮素,降钙素基因相关肽影响的实验观察.中国中医基础医学杂志,2001,7(5):60~62
8 何韵,罗斌.郑振声猪高脂血症心肌组织内皮素-1 的表达.中国法医学杂志.2004,19 增刊,5~7
9 张海涛,吴清玉.内皮素的临床研究进展.心血管病进展,1999,20(3):131~136
10 Wang BY,Ho HK,Lin PS,et al. Regression of atherosclerosis role of nitric oxide and apoptosis.Circulation,1999,99(9):1236~1238
11 马鲁波,刘剑刚,史大卓,等.气血并治方及其配伍对高脂血症血瘀大鼠血管活性物质的影响.中国实验方剂学杂志, 2006,12(4):32~35
12 雷燕,黄启福,王永炎,等.中药复圣散对高脂血症大鼠脑缺血再灌注后脑内若干神经肽含量的影响.中国中西医结合杂志,2000,20(3):205~207
13 褚田明,李明,陈国平.脑康防治动脉粥样硬化的实验研究.上海中医药杂志,1999,24(6):44~45
14 张文姚,任爱华,于澎.康复运动对冠心病患者血流动力学和前列环素,血栓素 A2 的影响.中国临床康复,2003,7 (24):3350~3351
15 陈汉斌,许家里,江洪,等.刺五加对冠心病患者的血浆血栓素 B2 和 6-酮-前列腺素 F1α 的影响.中国煤炭工业医学杂志, 2003,11(2):172~173
16 鞠宝兆.补肾活血方调脂作用的实验研究.中国临床康复2004,8(21):4266~4267
17 常小荣,严洁,岳增辉.隔药饼灸对高脂血症兔血浆前列环素和血栓素含量的影响.中国临床康复,2004,8(33):7446~ 7447
1 周美芳.从痰瘀论治高脂血症 88 例临床观察.贵阳中医学院学报,2005,27(1):43~45
2 张智勇,周若梅,刘娟云,等.调脂化瘀丸治疗高脂血症 302例.陕西中医,2006,27(11):1331~1332
3 叶勇.化痰活血法治疗高脂血症的机理探讨.陕西中医2005,26(11):1206~1208
4 杨秀捷,张晨,赵冰,等.从脾论治高脂血症 60 例临床观察.北京中医,2006,25(1):11~13
5 尹方,陈学忠,杨俐.从肾虚血瘀辨治高脂血症.Journal of Sichuan of Traditional Chinese Medicine,2006,24(1):25~26
6 王晓宁.针刺治疗高脂血症的临床观察.针灸临床杂志. 2005,21(9):9~10
7 邵明义,施斌,郑玉,等.痰瘀同治法在高脂血症治疗中的应用.河南中医,2005,25(3):60~62
8 胡皓,张玉.高脂血证的辨证治疗.河南中医,2003,23(10): 44~45
9 雷义举.中医辨证治疗高脂血症 82 例.陕西中医,2002,23 (6):507~508
10 丁宇炜,徐瑛,沈安,等.中医分型治疗高脂血症 45 例观察.内蒙古中医药,2003,(4):1~3
11 裴迅.活血通脉化痰汤治疗高脂血症的临床观察.湖北中医杂志,2006,28(2):31~32
12 毛大鹏,刘汝金,齐有胜.健脾利湿法法治疗高脂血症 42 例的临床观察,北京中医,2006,25(10):599~602
13 郜文辉,彭芝配,滕久祥.理气化痰祛瘀方治疗痰瘀互结型高脂血症的临床研究.湖南中医学院学报,2005,25(6):41~ 42
14 孙勇莉.降脂汤治疗高脂血症 52 例临床研究.河南中医学院学报,2003,18(4):47~48
15 刘红健,吴国珍.补肾活血法为主治疗高脂血症的临床研究.深圳中西医结合杂志,2003,13(1):33~34
16 崔春霞,崔佰宇.调理肝脾补肾法治疗老年人高脂血症 220例.河南中医学院学报,2006,21(3):51~53
17 朱立贤,金征宇.白藜芦醇苷对高脂血症大鼠血脂代谢的影响及其抗氧化作用.中成药,2006,28(2):260~261
18 成龙,梁日欣,杨滨.红花提取物对高脂血症大鼠降脂和抗氧化的实验研究.中国实验方剂学杂志,2006,12(9):25~27
19 刘海燕,石元刚.葛根素对高脂血症大鼠脂质代谢及血浆PGI2, TXA2 水平的影响.第三军医大学学报,2004,26(11): 967~969
20 张露芬,程金莲,严洁,等.电针心经腧穴对大鼠高血脂症血浆内皮素,降钙素基因相关肽影响的实验观察.中国中医基础医学杂志,2001,7(5):60~62
21 叶勇,梅国强,刘松林.化痰活血方对高脂血症大鼠血液流变学的影响.湖北中医学院学报,2005,7(3):11~13
22 郭洁文,廖惠芳,潘竞锵.荔枝核皂苷改善高脂血症-脂肪肝大鼠胰岛素抵抗作用的机制研究.中国药房,2005,16 (10):732~734
23 冯前进,薛征,关建红,等.杞蓉益精颗粒对高脂血症大鼠血清胆固醇浓度及其肝脏LDLR基因表达的影响.中国医药学报,2004,19(2):86~89