| Object:To investigate the protective effect of PCA on acute lung injury mice induced by LPS during ALI and its possible mechanism. And eplore the role of P38MAPK and TLR4 signaling pathway in ALI induced by LPS and treatment with PCA. And to study the effect of PCA on acute lung injury mice also treatment with SB203580 the blocker of P38MAPK and the expression of the both two signaling pathway.Method:Eighty Kunming mice were randomly divided into eight groups:normal control group(NC group),LPS group,the high doses of PCA pretreatment group, the middle doses of PCA pretreatment group, the small doses of PCA pretreatment group, SB203580 group, the dexamethasone positive control group, the PCA treatment combined with SB203580 group.ALI was induced by intraperitoneal injection of 5mg·kg-1 LPS. Mice were sacrificed at 6 hours, the lungs were harvested for observation of pathological changes. The total protein concentration in the bronchoalveolar lavage fluid and blood were observed by BCA method and the levels of TNF-α and IL-10β in serum of BALF were tested by ELISA. The expression of p38MAPK, p-p38MAPK, p-ATF2,TLR4 in lung tissue were detected by Western Blotting.Result:1.The result of pulmonary pathology:lung tissues from the control showed a normal structure and no histopathological changes under a light microscope. Compared with the control group, in the model group, there were significant lung structural damage, the histological results showed pulmonary alveolar hemorrhage, edema and inflammatory cell infiltration alveolar wall thickening, and even lung tissues destruction. PCA was significantly reduced the lung tissue damage and had a correlation with the PCA concentration, especially the high concentration group were best. LPS+ SB203580, LPS +Dex, LPS+ PCA+ SB203580 groups also found to reduce tissue damage compared with LPS group, a clear majority of alveolar structure, slightly thickened alveolar septa.2.Compared with the model group, the expression of TNF-a in BALF and the blood of PCA pretreatment were significantly decreased. And the decrease had a relation with the dose of PCA, the high dose of PCA group had the largest decline (P<0.05), has no significant difference compared with the normalgroup (P>0.05). The Blocker of SB203580 group, positive drug dexamethasone group and PCA joint with blocker group also showed the same effect, the TNF-a in BALF and blood were significantly lower than the LPS group (P<0.05).3.Compared with the model group, the expression of IL-1β in BALF and the blood of PCA pretreatment were significantly decreased. And the decrease had a relation with the dose of PCA, the high dose of PCA group had the largest decline (P<0.01), has no significant difference compared with the normalgroup (P>0.05). The Blocker of SB203580 group, positive drug dexamethasone group and PCA joint with blocker group also showed the same effect, the IL-1βin BALF and blood were significantly lower than the LPS group (P<0.05).4.Compared with the model group, the expression of the total protein in BALF of PCA pretreatment were significantly decreased. And the decrease had a relation with the dose of PCA, the high dose of PCA group had the largest decline (P<0.01), the low dose of PCA group had no significant difference compared with the normal group (P>0.05). The Blocker of SB203580 group, positive drug dexamethasone group and PCA joint with blocker group also showed the same effect, the the total protein in BALF were significantly lower than the LPS group (P<0.05).5.Compared with the normal group, the expression of the ratio of p-P38MAPK/P38MAPK of LPS group in lung tissue were significantly increased (P<0.01).And the expression of the p-P38MAPK/P38MAPK in PCA treatment groups were significantly decreased (P<0.01) And had a positive correlation with the dose of PCA. The Blocker of SB203580 group, positive drug dexamethasone group and PCA joint with blocker group also showed the same effect, the expression of the ratio of p-P38MAPK/P38MAPK in lung tissue were significantly lower than the LPS group (P<0.01).6.Compared with the normal group, the expression of the p-ATF2 in lung tissue of LPS group were significantly increased (P<0.01).And the expression of the p-ATF2 in PCA treatment groups were significantly decreased (P<0.01),and had a positive correlation with the dose of PCA. The Blocker of SB203580 group, positive drug dexamethasone group and PCA joint with blocker group also showed the same effect, the expression of the ratio of p-ATF2 in lung tissue were significantly lower than the LPS group (P<0.01).7.Compared with the normal group, the expression of the TLR4 in lung tissue of LPS group were significantly increased (P<0.01).And the expression of the TLR4 in PCA treatment groups were significantly decreased (P<0.01),and had a positive correlation with the dose of PCA. The Blocker of SB20358O group, positive drug dexamethasone group and PCA joint with blocker group also showed the same effect, the expression of the ratio of TLR4 in lung tissue were significantly lower than the LPS group (P<0.01).Conclusion:1. PCA has a protective effect on acute lung injury in mice induced by LPS.2. PCA’s protective effect on LPS-induced acute lung injury in mice has a positive correlationcon on the dose of PCA dose.3. PCA play a protective role on acute lung injury in mice induced by LPS by reducing the production of inflammatory mediators.4. PCA’s protective effect on acute lung injury in mice had a relation with suppressing the P38MAPK signaling pathway.5. PCA’s protective effect on acute lung injury in mice had a relation with suppressing the TLR4 signaling pathway.6. While pretreated with PCA and SB203580, the protective effect of PCA on LPS-induced acute lung injury in mice was weakened, that was further pointed that the protective effect of PCA on acute lung injury in mice had a relation with inhibiting the p38MAPK signaling pathway. |
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