参苓白术散对肺脾两虚型COPD大鼠十二指肠Ghrelin、Obestatin及其受体的影响  

Effects of Shen Ling Baizhu Prescription on duodenal Ghrelin,Obestatin and Their Receptors in Rats with Lung and Spleen Deficiency Type COPD

作　　者：桑凯 孙杰[1,2] 王东晓 马泉[1] 柳志清[1] SANGKai;SUN Jie;WANG Dongxiao;MA Quan;LIU Zhiqing(Gansu University of Chinese Medicine,Lanzhou 730000 Gansu,China;Affiliated Hospital of Gansu University of Chinese Medicine,Lanzhou 730020 Gansu,China)

机构地区：[1]甘肃中医药大学,甘肃兰州730000 [2]甘肃中医药大学附属医院,甘肃兰州730020

出　　处：《中药新药与临床药理》2018年第5期568-574,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金地区科学基金(81360539);甘肃省财政厅科研业务费项目(2013-9);兰州市科技局项目(2012-1-56)

摘　　要：目的观察参苓白术散对肺脾两虚型慢性阻塞性肺疾病(Chronic Obstructive Pulmonary Disease,COPD)模型大鼠十二指肠中生长激素释放肽(Ghrelin)、肥胖抑制素(Obestatin)及其受体(GHSR、GPR39)基因及蛋白表达的影响,基于Ghrelin-Obestatin信号通路探讨参苓白术散防治COPD的作用机制。方法将60只SPF级Wistar大鼠随机分为空白对照组、肺脾两虚观察组、药物干预组(根据药物干预时间不同,分为28 d、35 d、42 d组),每组12只。观察组及药物干预组采用烟熏+气管内滴注脂多糖+灌服冰冷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,分别于药物干预第28天、35天、42天测定各组大鼠肺功能并处死大鼠,采用RT-PCR法及免疫组化法测定大鼠十二指肠组织中Ghrelin,Obestatin及其受体GHSR、Obestatin m RNA及蛋白表达变化。结果与空白对照组相比,肺脾两虚观察组大鼠肺功能吸气气流高峰流速(PIF)、呼气气流高峰流速(PEF)频率(F)明显增高(P<0.05)、呼出50%气量时流速(EF50)、肺泡通气量(AV)明显下降(P<0.05);与肺脾两虚观察组相比,参苓白术散28 d组PIF、PEF、EF50、AV、F降低(P<0.05);参苓白术散35 d、42 d组PIF、PEF、EF50、F降低(P<0.05),AV升高(P<0.05)。与空白对照组相比,肺脾两虚观察组大鼠十二指肠组织中Ghrelin、GHSR、GPR39 m RNA表达减少(P<0.05),与肺脾两虚观察组相比,各药物干预组Ghrelin、GHSR、GPR39 m RNA表达水平升高(P<0.05)。与空白对照组相比,肺脾两虚观察组大鼠十二指肠组织中Ghrelin、GHSR、Obestatin、GPR39平均光密度明显降低(P<0.05),与肺脾两虚观察组相比,参苓白术散28 d组大鼠十二指肠中Ghrelin、GHSR、GPR39的变化无统计学意义(P>0.05);参苓白术散35 d组Ghrelin、GHSR、Obestatin的变化无统计学意义(P>0.05),参苓白术散42 d组Ghrelin、GHSR、Obestatin、GPR39平均光密度有所升高,差异有统计学意义(P<0.05)。结论参苓白Objective The effect of Shen Ling Baizhu prescription on the genes related to growth hormone releasing peptide（ghrelin）,obestatin and its receptor（GHSR,GPR39）in the duodenum of the rat model of chronic obstructive pulmonary disease（COPD）with lung and spleen deficiency was observed;the expression levels of ghrelin and obestatin and their receptors in the duodenum were detected.The mechanism of the method of reinforcing earth to generate metal by Ghrelin-Obestatin signal transduction pathways was analyzed.Methods Sixty SPF Wistar rats were randomly divided into blank control group,lung and spleen deficiency observation group and drug intervention groups（28 d,35 d and 42 d groups according to different drug intervention time）,12 rats in each group.Rats in the observation group and drug intervention group were smoked＋intratracheal instillation of lipopolysaccharide＋perfusion of cold senna extract to establish lung and spleen deficiency COPD rat models;rats in drug intervention groups were given Shen Ling Baizhu prescription.The rats were sacrificed on the 28th day,35th day and 42nd day.Rats’lung function was determined.RT-PCR and immunohistochemistry were used to determine the mRNA and protein expression levels of ghrelin,obestatin and GHSR and GPR39 in rats’duodenal tissue.Results Compared with the blank control group,lung-spleen deficiency group rats’PIF,PEF and F lung function were significantly higher（P〈0.05）;EF50,AV were significantly decreased（P〈0.05）.Compared withthe lung-spleen deficiency group,PIF,PEF,EF50,AV and F were decreased in the 28 d group（P〈0.05）.PIF,PEF,EF50 and F were decreased（P〈0.05）and AV was increased（P〈0.05）in the groups of 35 d and 42 d.Compared with the blank control group,the mRNA expression levels of ghrelin,GHSR and GPR39 in the duodenum of the lung-spleen deficiency group were decreased（P0.05）.Compared with the lung-spleen deficiency group,the mRNA levels of ghrelin,GHSR and GPR39 in all intervention groups were significantly h

关 键 词：肺脾两虚 COPD GHRELIN OBESTATIN 培土生金 参苓白术散 

分 类 号：R285.5[医药卫生—中药学]