Activation of Pink1/Parkin pathway alleviates the acute lung injury in exertional heat stroke rats
Objective To investigate the role of Pink 1/Parkin-induced mitophagy in acute lung injury of exertional heat stroke rats.Methods Sixty SD rats were randomly divided into four groups,including normal group(CON group),normal Parkin overexpression group(CON+Parkin group),heat stroke group(EHS group)and heat stroke Parkin overexpression group(EHS+Parkin group),with fifteen rats in each group.The rat model of exertional heat stroke was established and the survival curve was drawn.Pulmonary coefficient and pulmonary capillary permeability were detected.HE staining was used to observe the pathological changes of lung tissue.ELISA was used to detect the contents of IL-6,IL-1β,TNF-α and ROS in lung tissue;immunohistochemistry was used to observe apoptosis in lung tissue;Western blot was used to determine the expression of Pink1,Parkin,P62 and LC3 in rat lung tissue,and the LC3Ⅱ/LC3I ratio was calculated.Single factor multi-level group comparison was performed by single factor analysis of variance,SNK-q method was used to further pairwise comparison between groups.Results Compared with the normal group,the survival rate of EHS group was decreased(P＜0.001),lung coefficient and pulmonary vascular permeability were increased[(4.39±0.42),(33.38±8.29)μg/g,P＜0.05)],lung tissue was exudative and solid,the levels of inflammatory factors IL-6,IL-10,TNF-αand ROS were significantly increased[(34.31±5.34)μg/mL,(34.03±4.78)μg/mL,(91.64±8.16)μg/mL,(259.01±89.17)U/mg,P＜0.05)],and apoptosis was increased.Western and immunohistochemistry results showed that the expressions of Pinkl and Parkin were decreased,co-location of Pinkland Parkin was attenuated,LC3Ⅱ/LC3I were decreased,and P62 expression was increased.Compared with the EHS group,the survival rate of EHS+Parkin group was significantly increased(P＜0.05),lung coefficient and pulmonary vascular permeability were decreased[(3.83±0.62),(22.49±7.90)μg/g,P＜0.05)],exudation and consolidation and other pathological changes were significantly reduced,and the levels of the above inflammatory factors and ROS were significantly decreased[(14.09±3.24)μg/mL,(26.94±2.11)μg/mL、(63.35±11.62)μg/mL,(161.13±26.31)U/mg,P＜0.05].Lung tissue apoptosis was reduced.The co-location of Pinkland Parkin、Parkin expression and LC3Ⅱ/LC3Ⅰ ratio were increased(P＜0.05),P62 expression was decreased(P＜0.05),while Pinkl expression was not significant different(q=0.75).There was no difference between normal group and normal Parkin overexpression group(q=0.95).Conclusion Activation of Pink1/Parkin-induced mitophagy can alleviate the acute lung injury in exertional heat stroke rats.
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