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目的观察盐酸戊乙奎醚(PHC)对脂多糖(LPS)致大鼠急性肾损伤的作用,并探讨其对内毒素血症大鼠紧密连接闭锁小带蛋白(ZO-1)和紧密连接闭锁蛋白(Occludin protein)表达的影响。方法成年雄性SD大鼠随机分为对照组(C组)、LPS组(LPS组)、PHC低剂量组(L-PHC)和PHC高剂量组(H-PHC),每组10只,后3组注入LPS(5.0 mg/kg),30min后,L-PHC和H-PHC组分别注入PHC 0.3、0.9 mg/kg,24h后取外周血和肾组织,检测血清肌酐(Scr)、尿素氮(BUN)、TNF-α和IL-1β含量;蛋白免疫印迹法检测ZO-1和occludin蛋白的表达。结果 LPS组肾脏炎症明显,而L-PHC和H-PHC组肾脏炎症较弱;与C组比较,各组血浆TNF-α、IL-1β、Scr和BUN含量均显著升高(P<0.05),而L-PHC和H-PHC组其含量比LPC组明显降低(P<0.05);ZO-1和occludin蛋白表达水平LPS组升高,L-PHC和H-PHC组比LPS组下降(P<0.05)。结论 PHC可减轻脓毒症诱发的AKI,调控ZO-1和occludin蛋白的表达可能是其发挥保护作用的机制之一。
Objective To investigate the effect of penehyclidine hydrochloride (PHC) on acute renal injury induced by lipopolysaccharide (LPS) in rats and its effect on the expression of tight junctional zonules ZO-1 and tight junction blockade in endotoxemia rats. Protein (Occludin protein) expression. Methods Adult male Sprague-Dawley rats were randomly divided into control group (C group), LPS group (LPS group), PHC low dose group (L-PHC) and PHC high dose group The rats in L-PHC group and H-PHC group were injected with PHC 0.3 and 0.9 mg / kg respectively 30 min after injection of LPS (5.0 mg / kg). Peripheral blood and kidney tissue were taken after 24 h. Serum creatinine (Scr), urea nitrogen BUN), TNF-α and IL-1β were detected by Western blotting. Western blotting was used to detect the expression of ZO-1 and occludin. Results The renal inflammation in LPS group was obvious, while the renal inflammation in L-PHC group and H-PHC group was weaker. Compared with C group, the levels of TNF-α, IL-1β, Scr and BUN were significantly increased in each group (P < , While the content of ZO-1 and occludin in L-PHC and H-PHC groups was significantly lower than that in LPC group (P <0.05) <0.05). Conclusions PHC can attenuate sepsis-induced AKI. Regulating the expression of ZO-1 and occludin may be one of the protective mechanisms.