薯蓣皂苷元通过激活VIP/cAMP/PKA通路改善慢性阻塞性肺疾病大鼠气道炎症和肺损伤  

Diosgenin can improve airway inflammation and lung injury by activating VIP/cAMP/PKA signaling pathway in rats with chronic obstructive pulmonary disease

作　　者：甘平 黄颖 GAN Ping;HUANG Ying(Department of Respiratory and Critical Care Medicine,Chongqing Armed Police Corps Hospital,Chongqing 400061,China;Department of Geriatrics,Chongqing Armed Police Corps Hospital,Chongqing 400061,China)

机构地区：[1]武警重庆总队医院呼吸与危重症医学科,重庆400061 [2]武警重庆总队医院老年科,重庆400061

出　　处：《国际检验医学杂志》2023年第11期1323-1327,1333,共6页International Journal of Laboratory Medicine

摘　　要：目的探讨薯蓣皂苷元对慢性阻塞性肺疾病(COPD)大鼠及血管活性肠肽(VIP)/环磷酸腺苷(cAMP)/蛋白激酶A(PKA)通路的影响。方法将60只SD大鼠随机分为对照组、模型组、薯蓣皂苷元组(100 mg/kg)、阳性组(地塞米松0.81 mg/kg)、薯蓣皂苷元+H89组(100 mg/kg薯蓣皂苷元+1 mg/kg VIP/cAMP/PKA通路抑制剂H89),每组12只。4周后,采用全身体积描记系统检测大鼠肺功能,采用酶联免疫吸附试验检测大鼠血清中炎症因子水平及肺组织cAMP水平,采用HE染色检测肺组织病理变化,采用流式细胞术测定肺Th17、Treg细胞比例,采用蛋白质印迹法检测肺组织VIP、PKA蛋白表达。结果与对照组比较,模型组大鼠肺组织有炎症细胞浸润、部分血管破裂等损伤,炎症评分、白细胞介素(IL)-6、IL-8、肿瘤坏死因子-α(TNF-α)、IL-17、Th17细胞水平及Th17/Treg均升高(P<0.05),肺功能、Treg细胞、VIP、cAMP水平及p-PKA/PKA降低(P<0.05);与模型组比较,薯蓣皂苷元组、阳性组大鼠肺功能损伤缓解,炎症评分、IL-6、IL-8、TNF-α、IL-17、Th17细胞水平及Th17/Treg均降低(P<0.05),肺功能、Treg细胞、VIP、cAMP水平及p-PKA/PKA升高(P<0.05);与薯蓣皂苷元组比较,薯蓣皂苷元+H89组大鼠肺功能损伤加重,炎症评分、IL-6、IL-8、TNF-α、IL-17、Th17细胞水平及Th17/Treg升高(P<0.05),肺功能、Treg细胞、VIP、cAMP水平及p-PKA/PKA降低(P<0.05)。结论薯蓣皂苷元可能通过激活VIP/cAMP/PKA通路,改善COPD大鼠气道炎症和肺损伤。Objective To investigate the effects of diosgenin on chronic obstructive pulmonary disease(COPD)and vasoactive intestinal peptide(VIP)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway in rats.Methods A total of 48 SD rats were randomly divided into control group,model group,diosgenin group(100 mg/kg),positive group(dexamethasone 0.81 mg/kg),diosgenin+H89 group(100 mg/kg diosgenin+1 mg/kg VIP/cAMP/PKA pathway inhibitor H89).There were 12 rats in each group.Four weeks later,lung function was measured by body plethysmography.The levels of inflammatory factors in serum and cAMP in lung tissue were detected by enzyme-linked immunosorbent assay.The pathological changes of lung tissue were detected by HE staining.Flow cytometry was used to determine the proportion of Th17 and Treg cells in lung.The protein expressions of VIP and PKA in lung tissue were detected by Western blot.Results Compared with the control group,inflammatory cell infiltration and partial vascular rupture were observed in the lung tissue of the model group,and the inflammatory score,interleukin(IL)-6,IL-8,tumor necrosis factor-α(TNF-α),IL-17,Th17 cells levels and Th17/Treg were all increased(P<0.05),lung function,Treg cell VIP,cAMP levels and p-PKA/PKA ratio were significantly decreased(P<0.05).Compared with the model group,the lung function injury of the rats in the diosgenin group and the positive group was alleviated,and the inflammatory score,IL-6,IL-8,TNF-α,IL-17,Th17 levels and Th17/Treg were decreased(P<0.05),lung function,Treg cells,VIP,cAMP levels and p-PKA/PKA ratio were significantly increased(P<0.05).Compared with the diosgenin group,the lung function injury was aggravated in the diosgenin+H89 group,and the inflammatory score,IL-6,IL-8,TNF-α,IL-17,Th17 cells levels and Th17/Treg were increased(P<0.05),lung function,Treg cells,VIP,cAMP levels and p-PKA/PKA ratio were significantly decreased(P<0.05).Conclusion Diosgenin may improve airway inflammation and lung injury in COPD rats by activating VIP/cAMP/PKA pathway.

关 键 词：薯蓣皂苷元 血管活性肠肽/环磷酸腺苷/蛋白激酶A通路 慢性阻塞性肺疾病 肺损伤 炎症反应 

分 类 号：R392.11[医药卫生—免疫学]