Mechanism Of Rhubarb Regulating MTOR/HIF-1a/VEGF Signaling Pathway In The Treatment Of Acute Lung Injury

Purpose: To study whether rhubarb regulates mTOR/HIF-1α /VEGF signaling pathways as one of the mechanisms of prevention and treatment of Acute Lung Injury.Method:(1)Lipopolysaccharide(LPS)induced rat acute lung injury model were established in vivo experiments and the effects of rhubarb on the pathological morphology of lung tissue and the inflammatory factors TNF-α,IL-1β and IL-6 in bronchoalveolar lavage fluid were observed.(2)LPS induced cell model were established in vitro experiments to study the effects of rhubarb on the levels of TNF-α,IL-1β and IL-6 proteins and the regulation of mTOR/HIF-1α/VEGF signaling pathway.Result:(1)In vivo experiment results The pathological structure of lung tissue was observed under HE staining: local lung hemorrhage was observed in the lung tissue of the model group,the number of white blood cells in the pulmonary blood vessels was significantly increased,interstitial emphysema and inflammatory infiltration were observed;Pathological changes of lung tissue in the low dose group of rhubarb and high dose group of rhubarb were alleviated.Compared with the control group,the level of TNF-α,IL-6 and IL-1β in the bronchial lavage fluid of model group were significantly increased(P<0.05).Compared with the model group,the level of TNF-α in the low-dose rhubarb group was significantly decreased(P<0.05 or P<0.01),the protein level of IL-6 in high-dose rhubarb group was significantly decreased(P<0.05).(2)In vitro experiment results Compared with the control group,the level of TNF-α,IL-6 and IL-1β in the model group were significantly increased(P<0.05 or P<0.01).Compared with the model group,the level of IL-6 & IL-1β in the rhubarb 800ug/ml group was significantly decreased (P<0.05 or P<0.01).Compared with the control group,the m RNA expression of HIF-1a,e IF4 E & p70S6K1 in the model group was significantly increased(P<0.05 or P<0.01).Compared with the model group,in the rhubarb 200 ug/ml group,the m RNA expression of HIF-1a,p70S6K1 and e IF4 E was significant decreased(P<0.01);In the rhubarb 400ug/ml group,the m RNA expression of HIF-1a and p70S6K1 was significantly decreased(P<0.01);In the rhubarb 800ug/ml group,the m RNA expression of HIF-1a,p70S6K1 and e IF4 E was significantly decreased(P<0.01).Compared with the control group,the expression of HIF-1a and VEGF in the model group was significantly increased(P<0.05).Compared with the model group,the protein expression of VEGF in the rhubarb 200ug/ml group was significantly lower(P<0.05);In the rhubarb 400ug/ml group,the protein expression of P-mTOR and VEGF was significantly decreased(P<0.05 or P<0.01);In the rhubarb 800ug/ml group,protein expression of HIF-1a and VEGF was significantly decreased(P<0.05).Conclusion:(1)The pathogenesis of acute lung injury induced by LPS may be related to the increased expression levels of TNF-α,IL-1β and IL-6.(2)Rhubarb can reduce the pathological damage of lung tissue,and can decrease the protein level of TNF-α and IL-6 in bronchoalveolar lavage fluid of LPS-induced acute lung injury in rats.Rhubarb has protective effects on rats with acute lung injury caused by LPS,and its mechanism may be related to the decreased expression of TNF-α and IL-6.(3)Rhubarb can decrease the expression levels of TNF-α,IL-6 and IL-1β in LPS-induced cell RAW264.7 model,decrease the m RNA expression level of HIF-1a,e IF4 E and p70S6K1,decrease the protein expression of HIF-1a and VEGF;Rhubarb can decrease the expression levels of TNF-α,IL-6 and IL-1β in LPS-induced cell RAW264.7 model,which may related that the rhubarb can regulate the m RNA expression level of HIF-1a,e IF4 E,p70S6K1 and decrease the protein expression of HIF-1a and VEGF.