右美托咪定对脓毒症大鼠肝损伤过氧化物酶体增殖物激活受体和核转录因子活性的影响

Effect of dexmedetomidine on PPARγ/NF-κB activity in rats with sepsis under liver damage

目的评价右美托咪定对脓毒症大鼠肝损伤时过氧化物酶体增殖物激活受体(PPARγ)和核转录因子(NF)-κB活性的影响。方法将30只无特定病原体(SPF)级成年雄性SD大鼠,体质量230~250 g,按随机数字表法分成假手术组(Sham组)、模型组(M组)和右美托咪定组(D组),各10只。除Sham组外,脓毒症模型通过盲肠结扎和穿孔法建立的,Sham组通过剖腹手术暴露盲肠,不结扎,然后关闭腹部。D组经颈外静脉注射5μg/kg右美托咪定,10 min内注射完毕,之后以5μg·kg^(-1)·h^(-1)维持。Sham组、M组给予等剂量0.9%氯化钠注射液,各组均于皮肤缝合前停药。术后24 h,抽取血液检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、胆红素(BIL)浓度;酶联免疫吸附试验(ELISA)检测血清白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)浓度;采用苏木精-伊红(HE)染色法观察肝组织病理学结果并评分;蛋白质印迹法检测肝脏组织PPARγ、NF-κB、NF-κB抑制蛋白(ⅠκB)的表达。结果与Sham组比较,余组血清ALT、AST、BIL、IL-6、TNF-α浓度升高,肝组织损伤评分升高,肝脏PPARγ、ⅠκB蛋白表达下调,肝脏NF-κB表达上调(P<0.05);与M组比较,D组血清ALT、AST、BIL、IL-6、TNF-α浓度降低,肝组织损伤评分降低,肝脏PPARγ、ⅠκB蛋白表达上调,肝脏NF-κB表达下调(P<0.05)。结论右美托咪定可以减轻脓毒症大鼠肝损伤,其机制与通过PPARγ/NF-κB信号通路减轻其炎症反应有关。

Objective To evaluate the effect of Dexmedetomidine on PPARγ/NF-κB activity in rats with sepsis under l iver damage.Methods A total of 30 SPF-grade adult male SD rats,weighing 230-250 g,were randomly divided into sham operation group(Sham group),model group(M group),and dexmedetomidine group(D group)according to the random number table method.In addition to the Sham group,the sepsis model was estab-lished by cecal ligation and puncture method.The Sham group only exposed the cecum through laparotomy without ligation,and then closed the abdomen.The rats in D group were intravenously injected with 5μg/kg dexmedetomidine through the external jugular vein catheter,which was completed within 10 minutes,followed by maintenance dosing at 5μg·kg^(-1)·h^(-1).The Sham group and M group were given an equal dose of normal saline,and all groups stopped medication before skin suturing.At 24 hours postoperatively,blood samples were collected to measure the concentrations of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),and bilirubin(BIL).The concentrations of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The histopathological results of liver tissue were observed and scored using HE staining.The expression of PPARγ,nuclear NF-κB,and IκB(inhibitor of NF-κB)proteins in liver tissue was detected by Western blot.Results Compared with the Sham group,the concentrations of serum ALT,AST,BIL,IL-6,and TNF-αwere increased,the liver tissue injury score was elevated,the protein expression of PPARγand IκB in the liver was downregulated,and the expression of NF-κB in the liver was upregulated in the other groups(P<0.05).Compared with the M group,the concentrations of serum ALT,AST,BIL,IL-6,and TNF-αwere decreased,the liver tissue injury score was reduced,the protein expression of PPARγand IκB in the liver was upregulated,and the expression of NF-κB in the liver was downregulated in the D group(P<0.05).Conclusion Dexmedetomidine can alleviate liver injury in septic rats,and its mechanism is related to reducing inflammatory responses through the PPARγ/NF-κB signaling pathway.