桃红四物汤对慢性阻塞性肺疾病合并肺癌模型小鼠PI3 K/AKT信号通路的实验研究

Taohong Siwu Decoction Treats Chronic Obstructive Pulmonary Disease Complicated with Lung Cancer via the PI3K/AKT Signaling Pathway in Mice

目的观察桃红四物汤对慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)合并肺癌模型小鼠肺组织中磷脂酰肌醇3-激酶(Phosphoinositide3-kinase,PI3 K)、丝氨酸/苏氨酸激酶(Akt kinase,AKT)、p-PI3 K、p-AKT蛋白表达水平的影响,探讨桃红四物汤对COPD合并肺癌模型小鼠的影响及是否通过PI3 K/AKT信号通路参与调控。方法将80只SPF级C57/BL6小鼠按随机数字表法分为对照组、THSW组、Lewis组以及Lewis+THSW组,每组各20只。首先利用烟熏加LPS气道内滴注的方法对Lewis组、Lewis+THSW组小鼠建立小鼠COPD模型,模型验证成功后继续构建原位肺癌模型,最终建立COPD合并肺癌模型。对照组、Lewis组不做额外处理,THSW组、COPD+Lewis+THSW组每日进行灌胃给药,桃红四物汤剂量:4.5 ml/kg,1次/d,连续2周。末次经口灌胃给药后2 h,各组小鼠称重并记录;Lewis组和Lewis+THSW组小鼠的瘤体完整剥离并称重记录;免疫印迹法检测各组小鼠肺组织中PI3K、AKT、p-PI3K、p-AKT蛋白表达水平。结果与Lewis组比较,Lewis+THSW组的小鼠体质量有所提高,瘤重减轻,肺组织中PI3 K、AKT、p-PI3 K、p-AKT蛋白表达水平明显降低,差异有统计学意义(P<0.05)。结论桃红四物汤可能通过调控PI3 K/AKT信号通路发挥对COPD合并肺癌的治疗作用。

Objective To observe the effects of Taohong Siwu Decoction(THSW)on the expression of phosphoinositide 3-kinase(PI3 K),serine-threonine kinase(AKT),p-PI3 K,and p-AKT in the lung tissue of the mouse model of chronic obstructive pulmonary disease(COPD)complicated with lung cancer and explore the effect of THSW on the model mice and whether it participates in the regulation via PI3 K/AKT signaling pathway.Method Eighty SPF-grade C57/BL6 mice were randomized into control,THSW,Lewis,and Lewis+THSW groups(n=20).First,the mouse model of COPD was established by the method of smoking plus intratracheal instillation of lipopolysaccharide in the Lewis and Lewis+THSW groups.One week after the COPD model was successfully established,the model was combined with lung cancer in situ,and thus the model of COPD complicated with lung cancer was established.The mice in THSW and Lewis+THSW groups were administrated with THSW by gavage at 4.5 ml/kg,once per day for 2 consecutive weeks.Two hours after the last oral administration,the mice were weighed and recorded in each group.The tumors of mice in THSW and Lewis+THSW groups were completely collected and weighed.Western blotting was employed to determine the protein levels of PI3 K,AKT,p-PI3 K,and p-AKT protein in the lung tissue.Results Compared with the Lewis group,the Lew-is+THSW group showed increased body weight,decreased tumor weight,and down-regulated protein levels of PI3 K,AKT,p-PI3 K,and p-AKT in the lung tissue(P<0.05).Conclusion THSW may play a therapeutic role in COPD with lung cancer by regulating the PI3 K/AKT signaling pathway.