The Protective Effect Of Caveolin-1on Lung Injury In Rats Ventilated Through P38MAPK Signaling Pathway

Objective: To investigate the expression of caveolin-1under differentventilator conditions and to explain clearly the relationship between theexpressions of caveolin-1and the activation of P38MAPK signal in lung tissuein stress injury model.Methods:56adult male healthy SD rats were randomly divided into7groups（The weight of the SD rats are between220kg and330g），With the differenttidal volume(VT)，respiratory rate(RR)and duration of mechanical ventilationbetween each group： the control group (A) of normal breathing only to dotracheotomy； protective mechanical ventilation group (B1and B2group)，VT is the6ml/kg and RR is60bpm，B1group ventilation1h, B2groupventilation2h；Large-tidal volume ventilation group C1、C2、D1、D2(VT30ml/kg，RR40bpm，duration1h,2h)，but only the rat in group D1and D2wereinjected SB203580solution into enterocoelia. In the experiment，all the ratsin the7groups were given Hemodynamic monitoring and arterial blood gases.The group of A carved immediately bleeding to death after tracheal, the otherremaining rats in each group were sacrificed at a certain time of mechanicalventilation and pathological changes of lung tissue of rats were observed by Lightmicroscope and DAD score carried in each group. The protein expression ofcaveolin-1, P38MAPK and AP-1were measured By immunohistochemicalstaining. caveolin-1, P38MAPK,and MKK3mRNA’expression levels in lung tissuewere determined through (RT-PCR) reversetranscription-polymerase chainreaction. Wet to dry weight ratio (W/D) and medullary peroxidase (MPO) activitywere measured. Determination of the total protein and interleukin-6’(IL-6) levelsin bronchoalveolar lavage fluid (BALF) through enzyme—link immunosorbent assay（ELISA）.Results: Compared with normal control group A, The expression ofP38MAPK，MKK3，caveolin-1mRNA and caveolin-1,P38MAPK protein wasremarkably Increased while W/D ratio, MPO,DAD score，concentration ofIL-6in BALF and total protein increased in group C, however， AP-1proteinwas significantly down-regulated. Between group B、 C， expression ofP38MAPK，MKK3，caveolin-1mRNA and caveolin-1, P38MAPKprotein wassignificantly higher in group C than group of B while W/D ratio, MPO,DADscore，concentration of IL-6in BALF and total protein increased, but AP-1protein was significantly lower; Compared with group C， expression ofP38MAPK，MKK3mRNA and P38MAPK protein was significantly lower ingroup D while caveolin-1mRNA，caveolin-1and AP-1protein，W/D ratio,MPO,DAD score，concentration of IL-6in BALF and total protein increased.Conclusions: The activation of P38MAPK signal and cavreolin-1in lungtissue take part in the protection of the ventilator-induced lung injury.