High Molecular Weight Hyaluronan Attenuates Fine Particulate Matter Induced Acute Lung Injury And The Mechanism Research

Background:Inhalation of fine particulate matter(PM_2.5)is associated with lung injury.High molecular weight hyaluronan（HMW-HA）is an essential constituent of extracellular matrix（ECM）,exhibiting anti-oxidative and anti-inflammatory properties when administered by injection,inhalation,nebulization or gene delivery of HA synthases.Object:The aim of the present study is to determine whether HMW-HA alleviates PM_2.5-induced acute lung injury（ALI）and investigate the underlying mechanisms.Methods:in in vivo study,Male Sprague-Dwaley（SD）rats（180±20g）were weighted and randomly divided into three groups（n=6）:（1）intratracheal instillation of normal saline for 3 days（NS group）;（2）exposure to PM_2.5（8 mg/kg b.w.）and 200μL of saline by intratracheal instillation for 3 days(PM_2.5 group);（3）intratracheal instillation of PM_2.5suspension（8 mg/kg b.w.）and 200μL of 0.2%HMW-HA（1500 kDa-1700kDa）for 3 days(PM_2.5+HA group).Collected bronchoalveolar lavage fluid（BALF）was used to counting neutrophils and antioxidant assay.The lung tissues were perfused with 4%paraformaldehyde and embedded with paraffin for further histological analysis.In in Virto study,CCK-8 and Flow assay were used to detect the cell viability and apoptosis with difference HMW-HA concentration（0.1%;0.05%;0.025%）.The phosphorylation leaves of p38,JNK and ASK1 in cytoplasm were measured by Western Blot.Conclusion:The results elucidated that reactive oxygen species（ROS）was involved in PM_2.5-induced cell apoptosis,and HMW-HA mitigated the oxidative potential of PM_2.5,subsequently inhibiting phosphorylation of ASK1 at Thr845,downstream phosphorylation of p38 and JNK,and eventual apoptosis.