Effects of penehyclidine hydrochloride on expression of Toll like receptor-4 and nuclear factor kappa B in a rat model of sepsis-induced acute lung injury / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effects of penehyclidine hydrochloride (PHC) on the expression of Toll like receptor-4 (TLR4) and nuclear factor kappa B (NF-κcB) in a rat model of sepsis-induced acute lung injury (ALI).Methods Seventy-two adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =24 each) using a random number tableshame operation group (group S),ALI group and PHC group.Sepsis-induced ALl was induced by cecal ligation and puncture in anesthetized rats.In group PHC,PHC 0.45 mg/kg was intramuscularly injected immediately after cecal ligation and puncture.At 6,12,24 and 36 h after ligation,the broncho-alveolar lavage fluid (BALF) was collected for detection of TNF-α and IL-6 concentrations and the lungs were removed for determination of the expression of TLR4 (using RT-PCR and Western blot) and NF-κBp65 (using Western blot) in lung tissues and for microscopic examination.The pathological changes of lungs were scored.The wet to dry lung weight (W/D) ratio was calculated and the activity of myeloperoxidase (MPO) in lung tissues was measured.Results As compared with S group,the IL-6 concentrations in BALF at 6,12 and 24 h after ligation,TNF-α concentration in BALF at 6 and 12 h after ligation,and the expression of TLR4 and NF-κBp65,pathological scores,W/D ratio and MPO activity at each time point were significantly increased in ALI group (P ＜ 0.05).Compared with ALI group,the TNF-α concentration in BALF at 6 and 12 h after ligation,and IL-6 concentrations in BALF,the expression of TLR4 and NF-κBp65,pathological scores,W/D ratio and MPO activity at each time point were significantly decreased in group PHC (P ＜ 0.05).Conclusion PHC inhibits NF-κB activation and decreases inflammatory responses through blocking TLR4 expression in lung tissues,thus attenuating sepsis-induced ALI in rats.