黄柏碱改善脓毒症大鼠急性肾损伤的作用及机制研究

Effect and Mechanism of Phellodendrine on Acute Kidney Injury in Sepsis Rats

目的:考察黄柏碱对脓毒症大鼠急性肾损伤的保护作用及其机制。方法:取50只SD大鼠随机分为假手术组、模型组、黄柏碱低剂量组(100 mg/kg)、黄柏碱高剂量组(200 mg/kg)及氨苄青霉素钠组(150 mg/kg),每组10只。除假手术组外,各组采用盲肠结扎穿孔术(CLP)建立脓毒症大鼠模型。术后24 h,试剂盒检测血清肌酐(Cr)和尿素氮(BUN)的水平,ELISA法检测血清中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、肾损伤分子1(KIM-1)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α),HE染色法检测肾脏病变情况,免疫印迹法检测肾组织中Toll样受体4(TLR4)及Nod样受体蛋白3(NLRP3)蛋白的表达。结果:与脓毒症大鼠比较,黄柏碱可明显降低大鼠血清中Cr、BUN、NGAL及KIM-1含量,抑制炎性因子(IL-6、IL-1β及TNF-α)的释放,改善肾脏病理变化,同时可明显降低肾组织中TLR4及NLRP3的表达水平(P<0.05)。结论:黄柏碱可通过调控TLR4/NLRP3信号通路降低体内炎症因子水平,从而对脓毒症所致急性肾损伤发挥保护作用。

Objective To investigate the protective effect and mechanism of phellodendrine on acute kidney injury in sepsis rats.Methods Fifty SD rats were randomly divided into sham operation group,model group,phellodendrine low dose and high dose group(100 and 200 mg/kg),and ampicillin sodium group(150 mg/kg).Except the sham operation group,the sepsis rats were established by cecal ligation and perforation(CLP).After 24 h of surgery,the serum creatinine(Cr),urea nitrogen(BUN),neutrophil enzyme related lipid carrier protein gelatin molecule 1(NGAL),renal injury(KIM-1),interleukin 6(IL-6),interleukin 1 beta(IL-1β)and tumor necrosis factor alpha(TNF-α)were detected.HE staining was used to detect the kidney disease situation.WB method was used to detect the toll-like receptor 4(TLR4)and Nod like receptor protein 3(NLRP3)protein expression in renal tissue.Results Compared with the sepsis rats,the contents of Cr,BUN,NGAL and KIM-1 in serum of the rats were significantly reduced by phellodrine,which also inhibited the release of inflammatory factors(IL-6,IL-1βand TNF-α),improved renal pathological changes,and significantly reduced the expression levels of TLR4 and NLRP3 in renal tissues,(P<0.05).Conclusion Phellodendrine can regulate TLR4/NLRP3 signaling pathway and reduce the levels of inflammatory factors in vivo,so as to play a protective role in acute kidney injury caused by sepsis.