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阿魏酸钠磁性纳米颗粒对脓毒症肾损伤大鼠的保护作用

[Protective effect of sodium ferulate magnetic nanoparticle in septic kidney injury rats].

作者信息

Ma Qiang, Cieng Qing-Li, Ao Qiang-Guo, Yin Yan-Yan, Wen Jing, Qi Yun, Zhang Ying, Sheng Rong-Sheng

机构信息

Department of Geriatric Nephrology, PLA General Hospital, Beijing 100853, China.

Department of Pharmacology, College of Basis Medicine, Anhui Medical University, Hefei 230032, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2013 Sep;29(5):465-8.

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 lipolysaccharide (IPS) in rats in NE treatment group norepinephrine were used to elevate the blood pressure of septic rats, in NE + SF group sodium ferulate magnetic nanoparticle was injected via tail vein, magnetic field was placed near renal region. Urinary concentration of N-acetyl-beta-D-glucosaminidase (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.

摘要

目的

探讨阿魏酸钠磁性纳米粒靶向治疗对接受去甲肾上腺素治疗的脓毒症大鼠的肾脏保护作用。

方法

首先构建阿魏酸钠磁性纳米粒,将雄性Wistar大鼠随机分为4组(n = 6):对照组、脓毒症组、去甲肾上腺素治疗组(NE治疗组)和NE加阿魏酸钠磁性纳米粒治疗组(NE + SF组),通过静脉注射脂多糖(LPS)复制大鼠脓毒症模型,NE治疗组使用去甲肾上腺素升高脓毒症大鼠血压,NE + SF组经尾静脉注射阿魏酸钠磁性纳米粒,在肾区附近放置磁场。治疗3小时后测定尿中N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、肾损伤分子(KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(NGAL)浓度,肾组织丙二醛(MDA)、超氧化物歧化酶(SOD)浓度,以及血清血尿素氮(BUN)、肌酐(Cr)、谷丙转氨酶(ALT)、谷草转氨酶(AST)浓度。

结果

经尾静脉注射LPS后,脓毒症大鼠动脉收缩压、pH值、动脉血氧分压(PaO2)和动脉血二氧化碳分压(PaCO2)显著降低。去甲肾上腺素治疗后动脉收缩压、pH值、PaO2和PaCO2大致恢复至基线水平,阿魏酸钠磁性纳米粒靶向治疗未改变去甲肾上腺素的血流动力学效应。与对照组相比,脓毒症组尿NAG、KIM-1和NGAL显著升高(P < 0.01),去甲肾上腺素治疗后,NE治疗组尿NAG、KIM-1和NGAL较脓毒症组迅速升高(P < 0.01),联合阿魏酸钠磁性纳米粒靶向治疗,NE + SF组尿NAG、KIM-1和NGAL较脓毒症组和NE治疗组显著降低(P < 0.01)。与对照组相比,脓毒症大鼠肾组织MDA水平显著升高(P < 0.01),NE治疗较脓毒症组可显著升高MDA水平(P < 0.01),NE + SF组肾组织MDA水平较脓毒症组和NE治疗组显著降低(P < 0.01)。与对照组相比,脓毒症组和NE治疗组肾组织SOD活性显著降低(P < 0.01),阿魏酸钠磁性纳米粒靶向治疗后,NE + SF组肾组织SOD活性较脓毒症组和NE治疗组显著升高(与脓毒症组和NE治疗组相比,P < 0.01)。各组血清BUN、Cr、ALT、AST水平无显著变化。

结论

阿魏酸钠磁性纳米粒靶向治疗可有效降低脓毒症组和NE治疗组大鼠尿NAG、KIM-1、NGAL及肾组织MDA水平,提高组织SOD活性,从而保护脓毒症大鼠的肾功能。

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