Effect And Mechanism Of Jinshui Liujun Decoction In Treating Airway Mucus Retention In COPD Mic

Part 1 Meta analysis of modified Jinshui Liujun decoction in the treatment of COPDObjective:Systematically evaluate the clinical efficacy of modified Jinshui Liujun decoction in the treatment of COPD.Methods:China National Knowledge Infrastructure Platform for Computer Retrieval,Wanfang Data Knowledge Service Platform,VIP Chinese Journal Service Platform,and China Biomedical Literature Service System.Randomized controlled trials were collected on the treatment of COPD with Jinshui Liujun decoction.Two researchers independently screened,extracted,and evaluated the quality of the retrieved literature.Meta analysis and presentation were conducted using Review Manager(v5.4.1)software.Results:A total of 8 articles were included.Compared with conventional Western medicine treatment alone,patients with COPD treated with Jinshui Liujun decoction had a higher overall effective rate(OR=3.20,CI[1.99,5.15],Z=4.80,P<0.00001),FEV1(MD=0.23,CI[0.14,0.33],Z=4.83,P<0.00001),FEV1/FVC(MD=9.29,CI[6.35,12.23],Z=6.19,P<0.00001),FEV1/expected value(MD=5.59,CI[4.45,6.74],Z=9.57,P<0.00001)6MWD(MD=49.05,CI[38.78,59.32],Z=9.36,P<0.00001),Ig A(MD=0.24,CI[0.16,0.32],Z=5.56,P<0.00001),Ig G(MD=1.72,CI[1.14,2.29],Z=5.84,P<0.00001),and Ig M(MD=0.25,CI[0.18,0.33],Z=6.63,P<0.00001),And lower TCM syndrome scores(MD=-2.91,CI[-3.69,-2.12],Z=7.28,P<0.00001)and IL-6(MD=-1.05,CI[-1.51,-0.60],Z=4.56,P<0.00001).Conclusion:The clinical efficacy of Jinshui Liujun decoction in the treatment of COPD is better than that of traditional Western medicine alone.The outcome indicators include total effective rate,FEV1,FEV1/FVC,FEV1/predicted value,6MWD,traditional Chinese medicine syndrome score,Ig A,Ig G,Ig M,and IL-6,but higher levels of evidence-based medical evidence are still needed to verify.Part 2 Study on the Mechanism of Jinshui Liujun Decoction in Treating Airway Mucus Retention in COPD MiceObjective:To observe the effect of Jinshui Liujun decoction on airway mucus retention in mice with COPD and explore its possible mechanism.Methods:48 C57BL/6 mice were randomly divided into blank group,model group,Jinshui Liujun decoction group and N-acetylcysteine(NAC)group,with 12 in each group.The COPD mouse model was established by intranasal drip of LPS and smoking,and the corresponding drugs were given intragastric administration for 14 days after the model was established.The COPD mouse model was established by intranasal drip of LPS and smoking,and the corresponding drugs were given intragastric administration for 14 days after the model was established.The content of MPO,SA and Urea in alveolar lavage fluid(BALF)was detected by the kit,and the ratio of SA and Urea was calculated.The content of MUC5 AC in BALF was detected by ELISA.The levels of ROS,GSH,GSSG and GR in lung tissue were detected with the kit,and the ratio of GSH and GSSG was calculated.Western blot was used to detect the expression level of Keap1,CFTR,nuclear Nrf2 and cytoplasmic Nrf2 protein in lung tissue,and calculate the ratio of nuclear Nrf2 and cytoplasmic Nrf2.The expression level of CFTR m RNA in lung tissue was detected by q RT-PCR.Results:Compared with the blank group,the growth of the model group mice was poor,the body weight at each time point during the modeling period was reduced(P<0.01),the lung function indicators MV,PEF and PIF were reduced(P<0.01),the pathological score of lung tissue was increased(P<0.01),there was airway mucus retention and goblet cell proliferation(P<0.01),the levels of SA,SA/Urea,MUC5 AC and MPO in BALF were increased(P<0.01),the level of Urea was decreased(P<0.01),and the levels of ROS and GSSG were increased(P<0.01),The levels of GSH,GSH/GSSG and GR decreased(P<0.01),the expression of CFTR m RNA decreased(P<0.01),the levels of Nrf2,Nrf2/Keap1 and CFTR protein decreased(P<0.01),the level of Keap1 protein increased(P<0.01),the level of nuclear Nrf2 and cytoplasmic Nrf2 protein decreased(P<0.05),and the level of nuclear Nrf2/cytoplasmic Nrf2 protein had no significant difference(P>0.05).Compared with the model group,the growth condition of mice in the Jinshui Liujun Decoction and NAC groups improved,the body weight increased at all time points during the modeling period(P<0.05,P<0.01),the indexes of MV,PEF and PIF were significantly improved(P<0.01),the pathological score of lung tissue was decreased(P<0.01),the airway mucus retention and goblet cell proliferation were reduced(P<0.01),the levels of SA,SA/Urea,MUC5 AC and MPO in BALF were reduced(P<0.01),and the level of Urea was increased(P<0.01),The levels of ROS and GSSG in lung tissue decreased(P<0.01),as well as the levels of GSH,GSH/GSSG and GR increased(P<0.01),the expression level of CFTR m RNA in lung tissue increased,the levels of Nrf2,Nrf2/Keap1 and CFTR protein in lung tissue increased(P<0.01),and the level of Keap1 protein decreased(P<0.01),the level of nuclear Nrf2 and cytoplasmic Nrf2 protein increased(P<0.05),and the level of nuclear Nrf2/cytoplasmic Nrf2 increased(P>0.05).Conclusion:(1)Jinshui Liujun Decoction can improve COPD airway mucus retention by reversing the acquired defect of CFTR.(2)The antioxidant effect of Jinshui Liujun Decoction may be related to the regulation of Nrf2 signal pathway.(3)Jinshui Liujun Decoction and NAC can promote the expression of CFTR by increasing the nuclear transfer ratio of Nrf2,But further cell experiments are needed for verification.