The Protective Effects Of Penehyclidine Hydrochloride In Different Doses On Acute Lung Injury Induced By LPS In Rats

The Protective Effects of Penehyclidine Hydrochloride in Different Doses on Acute Lung Injury Induced by LPS in RatsObjective: To investigate the protective effect of penehyclidine hydrochloride (PHCD) in different doses on acute lung injury induced by LPS in ratsMethods: Sixty healthy SD rats of both sexes weighing 200 ~ 220 g were randomly divided into 5 groups (n = 12 each):groupⅠc ontro(lgroup C);groupⅡLPS;groupⅢ,ⅣandⅣ, PHCD 0.3, 1.0, 3mg/kg were given iv respectively after given LPS.Endotoxemia was induced by intraperitoneal lipopolysaccharide (LPS) 8mg/kg in groupⅡ, groupⅢ, groupⅣand groupⅣ. PHCD was infused intraperitoneal at 1 min after LPS administration in groupⅢ,ⅣandⅣ. The animals were anesthetized with pentobarbital sodium injection 35 mg/kg.The animals were killed at 6 h after IP LPS and the lungs were immediately removed for microscopic examination, detection of TLR4, TLR2 mRNA expression by RT-PCR, NF-κB p65 protein expression by Western-blotting.Blood samples were collected at 6 h after LPS administration for determination of serum TNF-α, IL-6 concentration by ELISA.Results: LPS significantly increased TLR4, TLR2mRNA, NF-κB p65 protein expression in the lung tissue and level of TNF-α, IL-6 in serum. Intraperitoneal PHCD 1.0 or 3.0 mg/kg significantly inhibited LPS–induced increase in TLR4, TLR2mRNA, NF-κB p65 protein expression in the lung tissue and level of TNF-α, IL-6 in serum.The inflammatory responses was significantly ameliorated in groupⅣandⅣas compared to group LPS and groupⅠ.Conclusion: PHCD(1.0, 3.0mg/kg)can down-regulation of TLR4, TLR2 mRNA expression, decrease NF-κB activity in the lung tissue and level of TNF-α, IL-6 in serum thus provides protective effect against acute lung injury rats induced by LPS.