Mechanism of PM2.5 on Brain and Kidney Injury in Rats Based on 5-LOX/LTB4 Signaling Pathway
Objective:The Nao(brain)-Shen(kidney)correlation theory in traditional Chinese medicine(TCM)posits that Nao and Shen are physiologically connected,share meridians,and interact through yin-yang responses.Based on this theory,the study aimed to investigate wheth-er inhalation of PM2 5 suspension at different doses caused damage to rat brain and kidney tissues through the activation of the 5-LOX/LTB4 pathway.This study also aimed to provide a biological basis for the Naoshenxiangguan theory and serve as a reference for experimental and clinical studies of related TCM drugs.Methods:SD rats were randomly divided into a normal control group and PM2 5 exposure groups at doses of 7.5,15,and 30 mg/kg,with 6 rats in each group.The rats in the exposure groups were treated with the corresponding dose of PM2 5 suspen-sion(1 mL/kg)via tracheal instillation once every 6 days for 3 months,while the control group received an equivalent volume of saline during the same period.The physiological conditions of the rats were recorded daily during the instillation period.After the final instillation,the rats were fasted for 12 hours before tissue collection.Renal histopathological section,24-hour urine volume,urine routine and serum renal function indexes BUN,SCR were employed to assess renal function impairment.Brain histopathological section and brain blood flow were used to assess the pathological damage in brain tissue.The expression levels of IL-1 β,IL-6,TNF-α,IL-10 and TGF-β1 in the serum and the protein expres-sions of 5-LOX and LTB4 in brain and kidney tissues were were analyzed to determine whether PM2 5 could induce systemic inflammation and activate the 5-LOX/LTB4 signaling pathway to cause inflammatory injury to rat brain and kidney tissues.Results:After intratracheal instilla-tion of different doses of PM2.5 suspension,rats in the model group,rats in the model groups showed dull and yellowish fur color,decreased food intake,and reduced body weight.Compared with the control group,rats in each PM2 5 exposure group showed varying degrees of edema and inflammatory cell infiltration in brain and kidney tissues.Urine volume,BUN and SCR levels were elevated to varying degrees in all model groups,with a significant increase observed in the PM2.5 15 and 30 mg/kg groups.Cerebral blood flow significantly decreased in all exposed groups.The expressions of IL-1β,IL-6 and TNF-α in the serum were significantly elevated(P＜0.01),while the expressions of IL-10 and TGF-β1 were significantly decreased(P＜0.01).The expressions of 5-LOX and LTB4 in brain and kidney tissues were significantly elevated(P＜0.01)in all exposed groups.Conclusion:Inhalation of PM2 5 can cause brain and kidney tissue damage.The mechanism may be related to the activation of 5-LOX/LTB4 signaling pathway after PM2 5-induced systemic inflammatory injury,which ultimately leads to inflammatory responses in the brain and kidney.
PM2.55-LOXLTB4Brain and kidney damageInflammatory injury
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