The Experimental Study Of The Expression And Function Of STAT3 In Acute Lung Injury

Objective: To investigate in acute lung injury (ALI) of rats whether cytokineIL-6 can active signal transducers and activators of transduction-3(STAT3). Byadministrating rapamycin(RPM) to block STAT3 gene expression ,to observe thechanges of bcl-2 and bax expression and to study whether the activiation ofSTAT3 is a antiapoptosic signal in acute lung. To provide a new approach andtheory for ALI treatment.Methods: Experiment includes two parts. 1 The expression of STAT3mRNA inALI: 30 healthy Wistar rats (190±10g) were randomly divided into 5 groups:NS group, ALI groups (LPS1h, LPS2h, LPS4h, LPS6h groups). Afterintravenous injection of endotixin (5mg/kg) from trail vein, animals were killedat 1th, 2th, 4th and 6th hour. Detection of STAT3 gene expression of lung tissuewith in situ hybridization(ISH) and measurement of the concentration of IL-6 inblood and BALF with radioimmunoassasy. 2 The effect of STAT3 activiation tobcl-2 and bax expression in ALI: 30 healthy Wistar rats were randomly dividedinto 5 groups: (1) NS group, LPS2h group, LPS4h group. After intravenousinjection of endotixin from trail vein, animals were killed at 2th, 4th hour.(2)Pretreatment with rapamycin 2h group and 4h group. Be certainSTAT3mRNA expression is significantly increased at 2th and 4th hour in ALI,hyperdermic injection of Rapamycin (0.5mg/kg) being done before 0.5 hours ofintravenous injection of endotixin and animals being killed at 2th, 4th hour afterintravenous injection of endotixin. To determinate STAT3mRNA expression byin situ hybridization and the expression of apoptosis related protein bcl-2, bax inlung constitition by immunohistochemistry technique.Results: After animals being injected LPS from trail vein, at 1th, 2th, 4th, 6thhour pathological changes of lung constitution alterate significantly.STAT3mRNA expression in lung constitution increased gradually, peaked at 4thhour and started to decrease at 6th hour. The change of IL-6 concentration inblood and BALF is consistent with the changes of STAT3mRNA expression, andthe two is positively correlated. In comparison with LPS groups, STAT3mRNAexpression in pretreatment with RPM groups was decreased. In the meantime,the bcl-2 expression is lower than in LPS groups, while the bax expression wasincreased.Conclusion: The experiental result shows the JAK-STAT3 pathway is activated atearly stage of ALI and IL-6 may activate STAT3 pathway to protect againstlung tissue; The activation of STAT3 pathway in ALI can increase bcl-2expression and decrease bax expression to protect against ALI apoptosis.