培土生金法对肺脾两虚型慢性阻塞性肺疾病模型大鼠血清Ghrelin、Obestatin及相关指标的影响
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摘要
目的:观察培土生金法代表方参苓白术散干预作用下肺脾两虚型慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)模型大鼠血清生长激素释放肽(Ghrelin)、肥胖抑制素(Obestatin)、瘦素及炎症因子的含量变化,探究培土生金法治疗COPD的作用机制,为该治法临床防治COPD提供理论依据。方法:60只Wistar大鼠随机分为空白组、模型组、药物干预组(根据药物干预时间的不同,分为参苓白术散28天、35天、42天组),每组12只。除空白组外,模型组及药物干预组大鼠给予烟熏+气管内注射脂多糖+灌服冰冷的番泻叶浸液建立肺脾两虚型COPD大鼠模型。药物干预组给予参苓白术散灌胃治疗,分别于药物干预第28天、35天、42天测定各组大鼠肺功能并取血处死,用ELISA法检测各组大鼠血清Ghrelin、Obestatin、瘦素及白细胞介素-1(IL-1)、肿瘤坏死因子-α(TNF-α)的含量变化。结果:与空白组比较,模型组大鼠呼吸频率F值升高,肺容量指标(TV)、流量指标EF50、肺动态顺应性Cdyn均明显降低(P<0.05);血清Ghrelin、Obestatin含量明显降低(P<0.05),IL-1、TNF-α、瘦素含量明显升高(P<0.05)。与模型组比较,药物干预组各时间点大鼠F值下降,TV、EF50、Cdyn值明显升高(P<0.05),血清Ghrelin、Obestatin含量不同程度升高(P<0.05),血清IL-1、TNF-α、瘦素含量明显下降(P<0.05)。与参苓白术散28天组比较,参苓白术散42天组F值、TNF-α下降,Cdyn、Obestatin含量升高(P<0.05)。结论:培土生金法可改善肺脾两虚型COPD大鼠营养不良状况,改善其肺功能,延缓COPD发展进程,其机制可能是上调其血清Ghrelin、Obestatin的表达和下调其血清中瘦素及炎症因子的表达;药物干预组的组间差异显示培土生金法的早期应用对COPD大鼠有保护作用,提示了培土生金法对COPD的防治作用。
Objective:Under the intervention of Shenling Baizhu powder,the representative prescription in the method of strengthening earth to generate metal,to observe the content changes of Ghrelin,Obestatin,leptin and inflammatory factors interleukin(IL)-1,tumor necrosis factor(TNF)-α in serum of model rats with chronic obstructive pulmonary diseases(COPD) of lung and spleen deficiency type,explore the mechanism of the method of strengthening earth to generate metal in treating COPD,and to provide theoretical basis for the method in clinical prevention and treatment for COPD. Methods: Divided 60 Wistar rats randomly into the blank group, the model group and the medicine intervention group based on the medicine intervention time subdivided into the 28 d,35 d and 42 d groups,12 rats in each group. Except the blank group,the rats in the model group and the medicine intervention group were given fumigation,endotracheal injection of lipopolysaccharide and infusion of cold folium sennae immersion liquid to establish models of rats with COPD of lung and spleen deficiency type. The medicine intervention group was additionally given Shenling Baizhu powder by gavage for treatment. On the 28 d,35 d and 42 d of medicine intervention, determined the lung function of rats in each group and sacrificed after draw blood. Detected content changes of Ghrelin,Obestatin,leptin,IL-1 and TNF-α in serum of rats in each group with Elisa method. Results:Compared with those in the blank group, the respiratory frequency(F value) in the model group was increased,while the indexes of lung volume(TV),the flow indexes(EF50) and the pulmonary dynamic compliance(Cdyn) were significantly reduced(P< 0.05); contents of Ghrelin and Obestatin in serum were obviously decreased(P < 0.05); contents of IL-1,TNF-α and leptin were remarkably increased(P < 0.05). Compared with those in the model group,F value of rats in every subgroups of the medicine intervention group was decreased,while values of TV,EF50 and Cdyn were significantly increased(P < 0.05);contents of Ghrelin and Obestatin in serum were increased in different degrees(P < 0.05);contents of IL-1,TNF-α and leptin in serum were obviously decreased(P < 0.05). Compared with the 28 d group of Shenling Baizhu powder,the F value and TNF-α in the 42 d group of Shenling Baizhu powder were decreased,while contents of Cdyn and Obestatin content were increased(P < 0.05). Conclusion:The method of strengthening earth to generate metal can improve the malnutrition condition of rats with COPD of lung and spleen deficiency type,improve the lung function and postpone the development process of COPD. The mechanism is probably to up-regulate the expression of Ghrelin and Obestatin in serum and to down-regulate the expression of leptin and inflammatory factors in serum. The intergroup difference in the medicine intervention group shows that the early application of the method of strengthening earth to generate metal has protective effect on rats with COPD,indicating the prevention and treatment for COPD of the method.
Objective:Under the intervention of Shenling Baizhu powder,the representative prescription in the method of strengthening earth to generate metal,to observe the content changes of Ghrelin,Obestatin,leptin and inflammatory factors interleukin(IL)-1,tumor necrosis factor(TNF)-α in serum of model rats with chronic obstructive pulmonary diseases(COPD) of lung and spleen deficiency type,explore the mechanism of the method of strengthening earth to generate metal in treating COPD,and to provide theoretical basis for the method in clinical prevention and treatment for COPD. Methods: Divided 60 Wistar rats randomly into the blank group, the model group and the medicine intervention group based on the medicine intervention time subdivided into the 28 d,35 d and 42 d groups,12 rats in each group. Except the blank group,the rats in the model group and the medicine intervention group were given fumigation,endotracheal injection of lipopolysaccharide and infusion of cold folium sennae immersion liquid to establish models of rats with COPD of lung and spleen deficiency type. The medicine intervention group was additionally given Shenling Baizhu powder by gavage for treatment. On the 28 d,35 d and 42 d of medicine intervention, determined the lung function of rats in each group and sacrificed after draw blood. Detected content changes of Ghrelin,Obestatin,leptin,IL-1 and TNF-α in serum of rats in each group with Elisa method. Results:Compared with those in the blank group, the respiratory frequency(F value) in the model group was increased,while the indexes of lung volume(TV),the flow indexes(EF50) and the pulmonary dynamic compliance(Cdyn) were significantly reduced(P< 0.05); contents of Ghrelin and Obestatin in serum were obviously decreased(P < 0.05); contents of IL-1,TNF-α and leptin were remarkably increased(P < 0.05). Compared with those in the model group,F value of rats in every subgroups of the medicine intervention group was decreased,while values of TV,EF50 and Cdyn were significantly increased(P < 0.05);contents of Ghrelin and Obestatin in serum were increased in different degrees(P < 0.05);contents of IL-1,TNF-α and leptin in serum were obviously decreased(P < 0.05). Compared with the 28 d group of Shenling Baizhu powder,the F value and TNF-α in the 42 d group of Shenling Baizhu powder were decreased,while contents of Cdyn and Obestatin content were increased(P < 0.05). Conclusion:The method of strengthening earth to generate metal can improve the malnutrition condition of rats with COPD of lung and spleen deficiency type,improve the lung function and postpone the development process of COPD. The mechanism is probably to up-regulate the expression of Ghrelin and Obestatin in serum and to down-regulate the expression of leptin and inflammatory factors in serum. The intergroup difference in the medicine intervention group shows that the early application of the method of strengthening earth to generate metal has protective effect on rats with COPD,indicating the prevention and treatment for COPD of the method.
引文
[1]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2013年修订版)[J].中国医学前沿杂志:电子版,2014,6(2):67-80.
[2]Emami A,Nazem R,Hedayati M.Is association between thyroid hormones and gut peptides,Ghrelin and Obestatin,able to suggest new regulatory relation between the HPT axis and gut?[J].Regulatory Peptides,2014,189:17-21.
[3]徐志松,包子予,王志英,等.慢性阻塞性肺疾病患者生长激素释放肽、生长激素、生长激素释放激素的变化及其临床意义[J].中华内科杂志,2012,51(7):536-539.
[4]Yi Lei,Yasha Liang,Yifan Chen,et al.Increased circulating Obestatin in patients with chronic obstructive pulmonary disease[J].Multidiscip Respir Med,2014,9(1):5.
[5]李航,黄慧婷,詹少锋,等.培土生金法治疗慢性阻塞性肺疾病稳定期疗效的Meta分析[J].广州中医药大学学报,2017,34(1):132-139.
[6]宋一平,崔德健,茅培英,等.慢性阻塞性肺疾病大鼠模型的建立及药物干预的影响[J].中华内科杂志,2000,139(8):556-557.
[7]张伟,宫静,张靖轩,等.一种肺脾两虚型慢阻肺动物模型的建立[J].辽宁中医杂志,2009,36(1):142-143.
[8]Inhff T,M?nnikes H,Noetzel S,et al.Desacyl Ghrelin inhibits the orexigenic effect of peripherally injected Ghrelin in rats[J].Peptides,2008,29(12):2159-2168.
[9]付荣国,袁浩铮,王莉,等.慢性肾功能不全大鼠下丘脑、胃肠道Ghrelin及其受体表达变化[J].南方医科大学报,2011,31(1):96-99.
[10]Andrews ZB.Central mechanisms involved in the orexigenic actions of Ghrelin[J].Peptides,2011,32(11):2248-2255.
[11]Xing YX,Yang L,Kuang HY,et al.Function of Obestatin in the digestive system[J].Nutrition,2017,34:21-28.
[12]Asakawa A,Inui A,Ksga T,et al.Ghrelin is appetite stimulatory signal from stomach with structural resemblance to motilin[J].Gastroenterology,2001,120:337-345.
[13]Pérez-Pérez A,Vilari?o-García T,Fernández-Riejos P,et al.Role of leptin as a link between metabolism and the immune system[J].Cytokine&Growth Factor Reviews,2017,35:71-84.
[14]Briggs DI,Lockie SH,Benzler J,et al.Evidence that diet-induced hyperleptinemia,but not haypothalamic gliosis,causes Ghrelin resistance in NPY/Ag RP neurons of male mice[J].Endocrinology,2014,155(7):2411-2422.
[2]Emami A,Nazem R,Hedayati M.Is association between thyroid hormones and gut peptides,Ghrelin and Obestatin,able to suggest new regulatory relation between the HPT axis and gut?[J].Regulatory Peptides,2014,189:17-21.
[3]徐志松,包子予,王志英,等.慢性阻塞性肺疾病患者生长激素释放肽、生长激素、生长激素释放激素的变化及其临床意义[J].中华内科杂志,2012,51(7):536-539.
[4]Yi Lei,Yasha Liang,Yifan Chen,et al.Increased circulating Obestatin in patients with chronic obstructive pulmonary disease[J].Multidiscip Respir Med,2014,9(1):5.
[5]李航,黄慧婷,詹少锋,等.培土生金法治疗慢性阻塞性肺疾病稳定期疗效的Meta分析[J].广州中医药大学学报,2017,34(1):132-139.
[6]宋一平,崔德健,茅培英,等.慢性阻塞性肺疾病大鼠模型的建立及药物干预的影响[J].中华内科杂志,2000,139(8):556-557.
[7]张伟,宫静,张靖轩,等.一种肺脾两虚型慢阻肺动物模型的建立[J].辽宁中医杂志,2009,36(1):142-143.
[8]Inhff T,M?nnikes H,Noetzel S,et al.Desacyl Ghrelin inhibits the orexigenic effect of peripherally injected Ghrelin in rats[J].Peptides,2008,29(12):2159-2168.
[9]付荣国,袁浩铮,王莉,等.慢性肾功能不全大鼠下丘脑、胃肠道Ghrelin及其受体表达变化[J].南方医科大学报,2011,31(1):96-99.
[10]Andrews ZB.Central mechanisms involved in the orexigenic actions of Ghrelin[J].Peptides,2011,32(11):2248-2255.
[11]Xing YX,Yang L,Kuang HY,et al.Function of Obestatin in the digestive system[J].Nutrition,2017,34:21-28.
[12]Asakawa A,Inui A,Ksga T,et al.Ghrelin is appetite stimulatory signal from stomach with structural resemblance to motilin[J].Gastroenterology,2001,120:337-345.
[13]Pérez-Pérez A,Vilari?o-García T,Fernández-Riejos P,et al.Role of leptin as a link between metabolism and the immune system[J].Cytokine&Growth Factor Reviews,2017,35:71-84.
[14]Briggs DI,Lockie SH,Benzler J,et al.Evidence that diet-induced hyperleptinemia,but not haypothalamic gliosis,causes Ghrelin resistance in NPY/Ag RP neurons of male mice[J].Endocrinology,2014,155(7):2411-2422.