Effects Of Melatonin Administration And Mechanisms On Ventilator-induced Lung Injury In Rats

OBJECTIVE Ventilator-induced lung injury(VILI)is one of the common respiratory complications in clinical anesthesia,and its prognosis is poor.Melatonin is a receptor-independent free radical scavenger,which is expressed in various tissues and cells.This study selected Sprague Dawley(SD)as the VILI model to explore the impact on the effects of melatonin pretreatment.Moreover,we analyzed the expression and significance of the expression of nuclear receptor ROR? and signal pathway RhoA/ROCK,and providing new evidence for the clinical treatment of VILI.Methods Forty healthy Sprague-Dawley(SD)rats were randomly divided into four groups(n=10).The Control group(group C)only was intubated.The model group(group ?),the MT treatment group(group MVI),and the MT+arachidonic acid(AA)group(group AVI)were exposed to the animal ventilator(VT 30ml/kg,40 breath/minute)for 4 hours.Group MVI was given with MT(20 mg/kg)by intraperitoneal injection 30 minutes before MV.Group AVI was given with MT(20 mg/kg)and AA(10mg/kg)by intraperitoneal injection 30 minutes before MV.Rats were sacrificed for four h after mechanical ventilation.The right lobe of the upper lung was fixed with 4%paraformaldehyde,paraffin-embedded sections,and HE morphological changes of the alveolar epithelial cells.The proper lung tissues were stored at-80?,and then Western Blot was used to determine the expression of ROR?,RhoA,ROCK.Moreover,the expression of IL-1?,IL-6,and IL-10 in BALF was analyzed through ELISA.Results 1.Compared with group C:the levels of IL-1? and IL-6 in group ? increased,but the levels of IL-10 decreased significantly(P<0.05).We also found that the expression of Rho A and ROCK protein increased(P<0.05),and the expression of RORa decreased(P<0.05).Microscopy results observed that lung tissue damage was evident in Group ?.The level of IL-10 levels in the MVI group was significantly increased(P<0.05),IL-1?,and IL-6 levels were not significantly different.Expression of RORa was upregulated(P<0.05),but expression of RhoA,ROCK were downregulated by MT pretreatment.2.Compared with VI group:the levels of IL-1? and IL-6 in BALF of MVI group decreased(P<0.05),IL-10 level increased(P<0.05),RORa expression level increased(P<0.05),lung injury Pathology score was significantly reduced(P<0.05).3.Compared with the MVI group:the levels of IL-1? and IL-6 in the alveolar lavage fluid of the AVI group were significantly increased(P<0.05),the difference was statistically significant,the IL-10 level was not statistically significant,RhoA,ROCK Significantly increased level(P<0.05).There is no significant difference in ROR? levelCONCLUSION:1.High mechanical ventilation caused severe lung injury,as evidenced by increases in inflammatory factors levels of IL-1? and IL-6 in BALF.The expression of RhoA and ROCK in lung tissue increased.2.Melatonin may stabilize the cytoskeletal structure to alleviate VILI by inhibiting the RhoA/ROCK signaling pathway.