青地合剂对肺癌患者放射性肺损伤的保护作用及其机制

PROTECTIVE EFFECT OF QINGDI MIXTURE AGAINST RADIATION-INDUCED LUNG INJURY IN PATIENTS WITH LUNG CANCER AND ITS MECHANISM

目的探讨青地合剂对放射性肺损伤(RILI)的保护作用及其机制,为青地合剂在临床中的推广使用提供科学依据。方法临床回顾性研究:分析了2016-2017年于我院放疗科接受胸部放射治疗的137例非小细胞肺癌患者的临床资料,放疗中应用青地合剂者(青地合剂组)71例,单纯放疗者(对照组)66例,比较两组患者的RILI发生率、发生时间、持续时间以及被迫中断放疗例数和不同时间点最大自主通气量实测值占预计值的百分比(MVV实/预%)、一秒用力呼气容积占用力肺活量的百分比(FEV1/FVC%)等肺功能情况。动物实验研究:45只C57BL/6小鼠随机分为空白对照组、单纯照射组以及青地合剂组。除空白对照组外,其余两组小鼠给予全胸部12 Gy照射,青地合剂组小鼠根据每周体质量变化每日1次给予青地合剂(0.02 mL/g)灌胃,连续用药4周,其余两组给予等量生理盐水,治疗4周后处死小鼠,取小鼠肺组织检测丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性,并观察小鼠肺组织病理变化情况。结果临床研究显示两组患者Ⅱ级以上RILI的发生率比较无明显差异(P>0.05),但青地合剂能推迟患者RILI的发病时间,且发病持续时间更短、被迫中断放疗例数更少(t=3.146、3.876,χ^2=5.011,P<0.05);肺功能检查显示,不同时间点及是否应用青地合剂和两者的交互作用均对患者的MVV实/预%以及FEV1/FVC%具有影响(F=6.327~8.224,P<0.05);应用青地合剂的患者放疗后MVV实/预%和FEV1/FVC%明显优于对照组(F=6.920、8.224,P<0.05)。动物实验结果显示,青地合剂组肺部炎症情况轻于单纯照射组。青地合剂组小鼠肺组织中的MDA含量明显低于单纯照射组,而SOD活性明显高于单纯照射组(F=9.352、6.774,P<0.05)。结论青地合剂对RILI具有一定的防护作用,其可能是通过上调肺组织中SOD活性及降低MDA含量,从而减轻辐射引起的肺部炎症反应而实现的。

Objective To investigate the protective effect of Qingdi mixture against radiation-induced lung injury(RILI)and its mechanism,and to provide a scientific basis for the clinical application of Qingdi mixture.Methods A retrospective ana-lysis was performed for the clinical data of 137 patients with non-small cell lung cancer who received chest radiotherapy in Department of Radiotherapy in our hospital from 2016 to 2017,and among these patients,71 were treated with Qingdi mixture(Qingdi mixture group)and 66 were treated with radiotherapy alone(control group).The two groups were compared in terms of the incidence rate,onset time,and duration of RILI and the number of patients who were forced to discontinue radiotherapy,as well as pulmonary function parameters including the ratio of the measured value of maximal voluntary ventilation(MVV)to its predicted value(MVV-measured/predicted%)and the ratio of forced expiratory volume in 1 second to forced vital capacity(FEV1/FVC%)at different time points.In the animal experiment,45 C57BL/6 mice were randomly divided into blank control group,irradiation group,and Qingdi mixture group.All mice except those in the blank control group were given whole chest irradiation at 12 Gy,and the mice in the Qingdi mixture group were given Qingdi mixture(0.02 mL/g)by gavage once a day for 4 weeks,according to the weekly change in body weight,while the mice in the other two groups were given an equal volume of normal saline.The mice were sacrificed after 4 weeks of treatment,and lung tissue samples were collected to measure the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD)and observe the pathological changes of lung tissue.Results The clinical study showed that there was no significant difference in the incidence rate of gradeⅡor above RILI between the two groups(P>0.05),but the Qingdi mixture group had a significantly longer time to the onset of RILI,a significantly shorter duration of the disease,and a significantly lower number of patients who were forced to discontinue radiotherapy(t=3.146,3.876,χ^2=5.011,P<0.05).The results of pulmonary function examination showed that time points,whether Qingdi mixture was used,and their interaction had significant influence on MVV-measured/predicted%and FEV1/FVC%(F=6.327-8.224,P<0.05),and compared with the control group,the Qingdi mixture group had significantly better MVV-measured/predicted%and FEV1/FVC%after radiotherapy(F=6.920,8.224,P<0.05).The results of the animal experiment showed that the Qingdi mixture group had significantly lighter pulmonary inflammation than the irradiation group,and compared with the irradiation group,the Qingdi mixture group had a significantly lower content of MDA and a significantly higher activity of SOD in lung tissue(F=9.352,6.774,P<0.05).\ConclusionQingdi Mixture has a certain protective effect against RILI,possibly by upregulating the activity of SOD and reducing the content of MDA in lung tissue and thus alleviating lung inflammation induced by irradiation.