The Therapeutic Effect Of ACEI And ARB Drugs On Pulmonary Fibrosis

Objective: To evaluate the efficacy of angiotensin converting enzyme inhibitors(ACEIs)and angiotensin II receptor blockers(ARBs)in the treatment of idiopathic pulmonary fibrosis and radiation-induced lung injury by systematic reviews.Animal experiments were performed to observe the pathological process of radiation-induced lung injury and to explore the effect of telmisartan on radiation-induced lung injury.Methods: 1.Systematic Evaluation: A computer-based search of PUBMED,EMBASE,THE COCHRANE Library,and CNKI,CBM,Wanfang and other databases.Using Revman 5.0 or NOS to assess the quality of the included literature.The stata 14.0 software was used to analyze the main indexes and auxiliary indexes extracted.The stata14.0 software was used to sort the results in the network meta analysis,and the grade of the evidence was scored by GRADE score.2.Animal experiment: 50 rats were randomly divided into five groups.Model electron linear accelerator irradiation,except for the blank control group each group irradiated a single absorbed dose of 20Cgy;each group on the first day after irradiation gavage,the middle dose group was given telmisartan 8mg / kg / d,The high dose group was given telmisartan 16 mg / kg / d,the prednisone group was given 10 mg / kg of prednisone,and the blank group and model group were given normal saline daily.The changes of rat activity and body weight were observed.At 3,7,14 and 28 days after irradiation,the rats were dissected,and the wet weight of the lungs were recorded,and the inflammation and fibrosis of the lung tissue were observed by HE and Masson staining.The expression of TGF-β and smad3 were detected by western blotting,and the molecular docking method was used to verify the mechanism of telmisartan in improving radiation-induced lung injury.Results: Meta-analysis 1: A total of 17 articles were included,14 ARBs and 3 ACEIs,altogether 1381 patients.Compared with the control group,ACEI and ARB drugs had an advantage in the treatment of idiopathic pulmonary fibrosis(RR=1.34,95%CI: 1.24-1.44,Z=7.81,P<0.001).Aided analysis of indicators showed that patients in the experimental group had significantly better partial pressure of oxygen(SMD=2.95,95%CI: 1.95 ~ 3.94,Z=5.82,P<0.001).The efficacy of telmisartan was better than that of other drugs(P<0.001),and the efficacy was better in patients <65 years(P<0.001)The partial pressure of blood carbon dioxide of telmisartan and valsartan improved significantly in the experimental group compared with the control group(SMD=-11.13,95%CI:-17.03 ~-5.24,Z=3.70,P<0.001).In addition,the carbon monoxide diffusion volume,the first second forced expiratory volume and lung capacity of the experimental group were all improved compared with the control group.The GRADE score for the relevant indicator shows that the quality rating is from low quality to medium quality.Meta analysis 2: ACEI drugs in the treatment of radiation pneumonitis can reduce the incidence of radiation-induced lung injury,but does not extend the patient’s survival time;statins and non-steroidal anti-inflammatory drugs protection rank Second only to ACEI drugs.Sensitivity analysis showed that the results were stable,and the therapeutic effect of ACEIs on radiation-induced lung injury was not affected by the gender and age of the patients.Animal experiments: Telmisartan can attenuate the lung inflammation and fibrosis in rats with acute radiation-induced lung injury,and improve the general state,body weight and lung coefficient of rats with radiation-induced lung injury and down-regulate the expression of TGF-β and smad3.The results of molecular docking show that there are intermolecular forces between telmisartan and 5 amino acids in the active pocket of TGF-β protein,which can form a stable conformation.Conclusion: 1.ACEI and ARB drugs have therapeutic effects on idiopathic pulmonary fibrosis,which can improve the curative effect of patients and improve the partial pressure of blood pressure and blood pressure of carbon dioxide.Among them,telmisartan is best,and patients who younger than 65 will benefit more,and its treatment has nothing to do with the duration of the disease.2.ACEI drugs have a good protective effect against radiation-induced lung injury,and the effect is better than statins and non-steroidal anti-inflammatory drugs.3.Telmisartan can down-regulate the expression of TGF-β and smad3,and protect acute radiation-induced lung injury.