【摘要】 目的:观察阿魏酸钠磁性纳米微粒靶向治疗对脓毒症模型大鼠急性肾损伤的肾保护作用。方法:构建阿魏酸钠磁性纳米微粒。将大鼠随机分为对照组、脓毒症组、去甲肾上腺素(NE)治疗组和阿魏酸钠磁性纳米微粒干预组(NE+SF)纳米微粒组(n=6),脂多糖(LPS)15 mg/kg静脉注射复制脓毒症大鼠模型,NE治疗组采用NE维持动脉压于基础值水平;阿魏酸钠磁性纳米微粒干预组(NE+SF纳米微粒组)给予阿魏酸钠磁性纳米微粒尾静脉注射,并在双侧肾区外加磁场。3 h后观察大鼠尿中N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、肾损伤分子-1(Kim-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平,肾组织丙二醛(MDA)、超氧化物歧化酶(SOD)及血清尿素氮(BUN)、肌酐(Cr)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平变化。结果:与对照组相比,脓毒症组大鼠尿中NAG、KIM-1、NGAL水平均显著升高(P<0.01),应用NE治疗后,与脓毒血症组相比,大鼠尿中NAG、KIM-1、NGAL水平进一步升高(P<0.01),加用阿魏酸钠磁性纳米微粒靶向治疗后,大鼠尿中NAG、KIM-1、NGAL水平均有显著下降(P<0.01)。与对照组比较,脓毒症组大鼠肾组织MDA水平显著升高(P<0.01),与脓毒血症组相比NE治疗组大鼠肾组织MDA水平进一步升高(P<0.05),加用阿魏酸钠磁性纳米微粒靶向治疗后,大鼠肾组织MDA水平较脓毒症组和NE治疗组均有一定程度的降低(P<0.01)。脓毒症组及去甲肾上腺素治疗组大鼠肾组织SOD水平显著降低(P<0.01),加用阿魏酸钠磁性纳米微粒靶向治疗后,大鼠肾组织SOD水平较脓毒症组和NE治疗组均有一定程度的升高(P<0.01)。各组大鼠血清BUN、Cr、ALT、AST水平均无明显变化。结论:阿魏酸钠磁性纳米微粒靶向治疗可显著降低脓毒症及NE治疗组大鼠尿中NAG酶、KIM-1、NGAL及肾组织MDA水平,提高肾组织SOD水平,发挥肾保护作用。更多还原

【Abstract】 Objective:To investigate the renal protective effect of sodium ferulate magnetic nanoparticle targeting therapy in septic rats receives norepinephrine treatment.Methods:First we constructed sodium ferulate magnetic nanoparticle,Wistar male rats were randomly divided into 4 groups( n = 6) :control group, septic group,norepinephrine treatment group( NE treatment group) and NE plus sodium ferulate magnetic nanoparticle treatment group( NE+SF group),septic rat model was reproduced by intravenous injection of LPS) in rats in NE treatment group norepinephrine were used to elevate the blood pressure of septic rats,in NE+SF group sodium ferulate magnetic manoparticle was injected via tail vein,magnetic field was placed near renal region.Urinary concentration of N-acetyl-β-D-glycosaminidase( NAG), kidney injury molecule( KIM-1) and neutrophil gelatinase-associated lipocalin( NGAL),renal tissue concentration of malonaldehyde( MDA),superoxide dismutase( SOD),and serum concentration of blood urea nitrogen( BUN),creatinine( Cr),alanine aminotransferase( ALT),aspartate aminotransferase( AST) were measured 3 hours after treatment.Results:After injected LPS via tail vein,systolic blood pressure,pH value,PaO2 and PaCO2 of arterial blood of septic rats decreased significantly.Systolic blood pressure,pH value,PaO2 and PaCO2 of arterial blood returned to baseline approximately after norepinephrine treatment,sodium ferulate magnetic nanoparticle targeting therapy did not change hemodynamic effects of norepinephrine.Compared with control group,urine NAG,KIM-1 and NGAL of sepsis group were increased significantly( P < 0.01),after treatment with norepinephrine,urine NAG,KIM-1 and NGAL of NE treatment group were elevated rapidly compared with those of sepsis group( P < 0.01),combined with sodium ferulate magnetic nanoparticles targeting treatment,urine NAG,KIM-1 and NGAL of NE+SF group were decreased significantly compared with those of sepsis group and NE treatment group( P < 0.01).Compared with control group,renal tissue MDA levels of septic rats increased significantly( P < 0.01),NE treatment could notably raise MDA levels compared with those of sepsis group( P < 0.01),renal tissue MDA levels of NE+SF group were decreased significantly compared with those of sepsis group and NE treatment group( P < 0.01).Compared with control group,renal tissue activities of SOD of sepsis group and NE treatment group were decreased significantly( P < 0.01),after targeted treatment with sodium ferulate magnetic nanoparticle, renal tissue SOD activities of NE+SF group increased significantly compared with those of sepsis group and NE treatment group( P < 0.01 vs sepsis group and NE treatment group).Serum BUN,Cr,ALT,AST levels did not significantly change in each groups.Conclusion:Sodium ferulate magnetic nanoparticle targeting therapy can effectively decrease urine NAG,KIM-1,NGAL and renal tissue MDA level,increase tissue SOD activity of sepsis group and NE treatment group rats,thus protect renal function of septic rats.更多还原