盐酸戊乙奎醚对内毒素血症大鼠紧密连接蛋白表达的影响

Effect of penehyclidine hydrochloride on expression of tight junction proteins of endotoxemia rats induced by lipopolysaccharide

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 explore the effects of penehyclidine hydrochloride on expression of tight junction proteins ofendotoxemia rats with acute renal injury induced by lipopolysaccharide. Methods Adult male SD rats were randomly dividedinto control group（group C）,LPS group（LPS group）, PHC low-dose group（L-PHC）and PHC high-dose group（H-PHC）,n = 10,rats in the 3 latter groups were injected with LPS（5.0 mg / kg）,30 min later,rats in L-PHC and H-PHC group wereinjected with PHC 0.3,0.9 mg / kg;The peripheral blood and kidney tissues of the rats were obtained to measure the levels ofserum creatinine（Scr）,blood urea nitrogen（BUN）, TNF-α and IL-1β content 24 h later;Western-blot was used to detect theexpression of ZO-1 and occludin protein. Results Kidney inflammation in rats of LPS group was serious,while that in L-PHC and H-PHC group was mild;Compared with group C, the levels of serum TNF-α,IL-1β,Scr and BUN in rats of LPSgroups were significantly increased（P〈0.05）whereas that in rats of L-PHC and H-PHC group were significantly decreased,compared with LPS group（P〈0.05）; Expressions of ZO-1 and Occludin in rats of LPS group elevated and that in L-PHC andH-PHC group were decreased（P〈0.05）. Conclusion PHC can reduce endotoxemia-induced AKI,and the protection maybe related to its regulation of the expression of ZO-1 and occludin protein.