肝与衰老相关性的理论及实验研究
摘要
目的 在中医理论指导下,探讨肝与衰老的密切关系,并通过实验研究进一步明确其相关性的机制,以便为从肝延缓衰老提供理论和实验依据。本文分为理论探讨和实验研究两大部分。
理论探讨 人体衰老,肝为先导。肝性主动,与脾肾有着密切联系。肝主疏泄,推动脾运,肝主藏血,精血同源,同为人体防病抗衰的重要物质。肝失疏泄,内生痰瘀。血与津液是人体重要的物质基础,其输布依赖气的推动,肝失疏泄,血与津液代谢障碍形成痰浊、瘀血,病理产物的形成是人体变生它证,加快衰老。肝气逆乱,为五脏之贼。肝为将军之官,其性急躁刚勇,其病涉及乘土、刑金、冲心、耗肾之变。情志失调,易致衰老。肝主疏泄,调畅情志。疏泄失常,肝气郁结可致情志抑郁,而情志失调,气机郁滞,加速衰老。
实验研究 方法:我们使用D—半乳糖颈背部皮下注射来制作衰老的动物模型。在此基础上应用调肝治疗对模型进行了治疗作用的实验研究。将昆明小鼠随机分为正常组、模型组、维生素E-C组、调肝小剂量组、调肝大剂量组。结束给药后,检测调肝治疗对衰老小鼠自由基、心钠素、降钙素基因相关肽,肝细胞凋亡以及超微结构的影响。结果:1、调肝治疗对衰老小鼠肝组织自由基的影响,调肝治疗能有效地减少衰老小鼠肝组织中的MDA含量,提高SOD含量;2、调肝治疗对衰老小鼠肝组织超微结构的影响,调肝治疗对衰老小鼠肝组织超微结构的病理改变有所改善。3、调肝治疗对衰老小鼠血浆心钠素、降钙素相关基因肽的影响,调肝治疗能显著提高衰老小鼠血浆降钙素相关基因肽的含量,降低心钠素含量。4、调肝治疗对衰老小鼠肝细胞凋亡的影响,调肝治疗能抑制细胞凋亡。结论:模型组小鼠的肝组织中有SOD含量降低、MDA含量增加等表现,说明已经成功地复制了衰老的动物模型。调肝治疗能有效地减少肝组织中自由基含量、提高血浆降钙素相关基因肽含量,降低血浆心钠素含量,有效调节血液循环,抑制细胞凋亡,有延缓衰老的作用。
Object: Probing the close relationship between liver and aging under the direction of TCM theory , then through experiment study , to confirm the mechanism of the correlativity , so as to offer warranty of theory and experiment for postpone aging from liver .The text was divided into two parts: theory probing and experiment study .Theory probing: liver and aging have close relationship through the study of ancient words. The liver called general organ governs the normal flow of Qi and stores blood. 1. The character of liver is active, it connects the congenital and the acquired, so liver is the important factor at the beginning of aging. 2. The liver is responsible for the smoothly ascending and spreading movements of Qi in the body. The dysfunction of the liver would lead to the obstraction of the movement of Qi, the blood stasis andthe phlegm may occur. These are internal pathogenic factors, could cause rhe pathological aging. 3. The temper of the liver is impetuous and firmly, it used to infect other organs, such as kidney、 spleen、 lung and heart. The liver is called "a black sheep" because of it. 4. The liver regulates the mood. The mental activities of human beings depend on the
unobstructed movement of Qi and blood, especial Qi. Abnormal mood cause the movement of Qi unbalance. Many disease are based on disobey of Qi. Sometimes uncontroled mood brings the irregulate of the liver, sometimes disadjust mood due to the dysfunction of the liver.Experiment studyMethods: The mice were randomly divided into five groups: normal control group; model group; Vitamin E-C group; regulating liver low dose group and regulating liver large dose group.The aging rat model was induced by subcutaneous injection of 2%D-Galactose on the back near neck 100mg/kg/d for four weeks and others by 0.9% sodium chloride. Then feed the Vitamin E-C group Vitamin E-C 1.5g/kg.d ,feed the regulating liver low dose group 1.25g/kg.d herd medcined and the regulating liver large dose group 3.75g/kg/d ,the other 0.9% sodium chloride for 4 weeks. We observed MDA, SOD, ANP, CGMP, apoptosis of hepatic cell and ultrastructure changes.Results: 1. Compared with the indexes of the regulating liver groups and Vitamin E-C group and normal control group, modle group revealed the level of SOD in liver tissue (171.6267±18.0425,174.1233±19.3208, 176.748±29.0893,180.464±29.9301 vs 141.523±23.5483,p<0.01,p<0.05 )reduced and the level of MDA in liver tissue (6.3825±0.7285, 6.8558±0.3878, 6.567±0.7894,7.017±0.5345 vs 8.894±0.6133,P<0.01
) increased. 2. regulating liver groups all can decreased obviously in serum ANP(133.3281±80.1879, 147.1493±71.7597 vs 559.2754±116.1705, 575.2104±319.192, 380.2496+358.8657, P (0.01, P (0.05) .And can increased the level of serum CGRP (221.9872±44.1605, 214.8828+116.2725 vs 172.149±43.7388, 158.7331±52.0614, 143.291±25.7986,P<0.01). 3. There were obviously apoptosis in model group; regulating liver can decrease the rate of hetepic apoptosis(26.92±3.18,30.07+3.43 vs 36.71±2.31,P<0.01) .there is significant different between high dose regulating liver group and low dose regulating liver group(26.92±3.18 vs 30.07±3.43,P<0.05) 4. Regulating liver can obviously improve the ultrastructure pathological changes made by D-Galactose.Conclusion: There were many changes in model group, such as: the decrease of SOD, the increase of MDA, ultrastructure pathological changes etc. It means the aging model was successfully founded. Regulating liver therapy can decrease the level of free radical, restrain apoptosis, improve blood circulation, though these it can postpone aging.
理论探讨 人体衰老,肝为先导。肝性主动,与脾肾有着密切联系。肝主疏泄,推动脾运,肝主藏血,精血同源,同为人体防病抗衰的重要物质。肝失疏泄,内生痰瘀。血与津液是人体重要的物质基础,其输布依赖气的推动,肝失疏泄,血与津液代谢障碍形成痰浊、瘀血,病理产物的形成是人体变生它证,加快衰老。肝气逆乱,为五脏之贼。肝为将军之官,其性急躁刚勇,其病涉及乘土、刑金、冲心、耗肾之变。情志失调,易致衰老。肝主疏泄,调畅情志。疏泄失常,肝气郁结可致情志抑郁,而情志失调,气机郁滞,加速衰老。
实验研究 方法:我们使用D—半乳糖颈背部皮下注射来制作衰老的动物模型。在此基础上应用调肝治疗对模型进行了治疗作用的实验研究。将昆明小鼠随机分为正常组、模型组、维生素E-C组、调肝小剂量组、调肝大剂量组。结束给药后,检测调肝治疗对衰老小鼠自由基、心钠素、降钙素基因相关肽,肝细胞凋亡以及超微结构的影响。结果:1、调肝治疗对衰老小鼠肝组织自由基的影响,调肝治疗能有效地减少衰老小鼠肝组织中的MDA含量,提高SOD含量;2、调肝治疗对衰老小鼠肝组织超微结构的影响,调肝治疗对衰老小鼠肝组织超微结构的病理改变有所改善。3、调肝治疗对衰老小鼠血浆心钠素、降钙素相关基因肽的影响,调肝治疗能显著提高衰老小鼠血浆降钙素相关基因肽的含量,降低心钠素含量。4、调肝治疗对衰老小鼠肝细胞凋亡的影响,调肝治疗能抑制细胞凋亡。结论:模型组小鼠的肝组织中有SOD含量降低、MDA含量增加等表现,说明已经成功地复制了衰老的动物模型。调肝治疗能有效地减少肝组织中自由基含量、提高血浆降钙素相关基因肽含量,降低血浆心钠素含量,有效调节血液循环,抑制细胞凋亡,有延缓衰老的作用。
Object: Probing the close relationship between liver and aging under the direction of TCM theory , then through experiment study , to confirm the mechanism of the correlativity , so as to offer warranty of theory and experiment for postpone aging from liver .The text was divided into two parts: theory probing and experiment study .Theory probing: liver and aging have close relationship through the study of ancient words. The liver called general organ governs the normal flow of Qi and stores blood. 1. The character of liver is active, it connects the congenital and the acquired, so liver is the important factor at the beginning of aging. 2. The liver is responsible for the smoothly ascending and spreading movements of Qi in the body. The dysfunction of the liver would lead to the obstraction of the movement of Qi, the blood stasis andthe phlegm may occur. These are internal pathogenic factors, could cause rhe pathological aging. 3. The temper of the liver is impetuous and firmly, it used to infect other organs, such as kidney、 spleen、 lung and heart. The liver is called "a black sheep" because of it. 4. The liver regulates the mood. The mental activities of human beings depend on the
unobstructed movement of Qi and blood, especial Qi. Abnormal mood cause the movement of Qi unbalance. Many disease are based on disobey of Qi. Sometimes uncontroled mood brings the irregulate of the liver, sometimes disadjust mood due to the dysfunction of the liver.Experiment studyMethods: The mice were randomly divided into five groups: normal control group; model group; Vitamin E-C group; regulating liver low dose group and regulating liver large dose group.The aging rat model was induced by subcutaneous injection of 2%D-Galactose on the back near neck 100mg/kg/d for four weeks and others by 0.9% sodium chloride. Then feed the Vitamin E-C group Vitamin E-C 1.5g/kg.d ,feed the regulating liver low dose group 1.25g/kg.d herd medcined and the regulating liver large dose group 3.75g/kg/d ,the other 0.9% sodium chloride for 4 weeks. We observed MDA, SOD, ANP, CGMP, apoptosis of hepatic cell and ultrastructure changes.Results: 1. Compared with the indexes of the regulating liver groups and Vitamin E-C group and normal control group, modle group revealed the level of SOD in liver tissue (171.6267±18.0425,174.1233±19.3208, 176.748±29.0893,180.464±29.9301 vs 141.523±23.5483,p<0.01,p<0.05 )reduced and the level of MDA in liver tissue (6.3825±0.7285, 6.8558±0.3878, 6.567±0.7894,7.017±0.5345 vs 8.894±0.6133,P<0.01
) increased. 2. regulating liver groups all can decreased obviously in serum ANP(133.3281±80.1879, 147.1493±71.7597 vs 559.2754±116.1705, 575.2104±319.192, 380.2496+358.8657, P (0.01, P (0.05) .And can increased the level of serum CGRP (221.9872±44.1605, 214.8828+116.2725 vs 172.149±43.7388, 158.7331±52.0614, 143.291±25.7986,P<0.01). 3. There were obviously apoptosis in model group; regulating liver can decrease the rate of hetepic apoptosis(26.92±3.18,30.07+3.43 vs 36.71±2.31,P<0.01) .there is significant different between high dose regulating liver group and low dose regulating liver group(26.92±3.18 vs 30.07±3.43,P<0.05) 4. Regulating liver can obviously improve the ultrastructure pathological changes made by D-Galactose.Conclusion: There were many changes in model group, such as: the decrease of SOD, the increase of MDA, ultrastructure pathological changes etc. It means the aging model was successfully founded. Regulating liver therapy can decrease the level of free radical, restrain apoptosis, improve blood circulation, though these it can postpone aging.
引文
[1] 张茂林、张六通、邱幸凡.中医学衰老理论探讨.湖北中医杂志.2001、23(9):9-11
[2] 李晓康.人之衰老,肝为先导.天津中医学院学报.1999,18(3):3-5
[3] 杨维益,王天芳,等.肝脏在五脏中的地位演变.中国医药学报.1995,10(3):10-13
[4] 孙益鑫.试论“肝为万病之贼”.安徽中医学院学报.1997,16(2):2-4
[5] 李峰,杨维益,等.从中医学看肝脏调节应激反应的作用.北京中医药大学学报,1998,21(1):20
[6] 陈家旭.论肝为气血调节之枢.中医杂志.1998,39(1):9-12
[7] 田进文.论肝失疏泄与人体平滑肌功能态的关系.山东中医药大学学报.1998,22(3):201-205
[8] 徐中环.衰老亦责之于肝郁.成都中医药大学学报.1998,20(2):8-10
[9] 王玉芳,路永超.试论肝与衰老的关系.山东中医药大学学报.2002,26(4):249-251
[10] 黎鹏程,皮明钧,李定祥.延缓衰老从肝调理探讨.辽宁中医杂志.2001,28(5):262-263
[2] 李晓康.人之衰老,肝为先导.天津中医学院学报.1999,18(3):3-5
[3] 杨维益,王天芳,等.肝脏在五脏中的地位演变.中国医药学报.1995,10(3):10-13
[4] 孙益鑫.试论“肝为万病之贼”.安徽中医学院学报.1997,16(2):2-4
[5] 李峰,杨维益,等.从中医学看肝脏调节应激反应的作用.北京中医药大学学报,1998,21(1):20
[6] 陈家旭.论肝为气血调节之枢.中医杂志.1998,39(1):9-12
[7] 田进文.论肝失疏泄与人体平滑肌功能态的关系.山东中医药大学学报.1998,22(3):201-205
[8] 徐中环.衰老亦责之于肝郁.成都中医药大学学报.1998,20(2):8-10
[9] 王玉芳,路永超.试论肝与衰老的关系.山东中医药大学学报.2002,26(4):249-251
[10] 黎鹏程,皮明钧,李定祥.延缓衰老从肝调理探讨.辽宁中医杂志.2001,28(5):262-263