蛋白质氧位N-乙酰葡萄糖胺修饰对脓毒症大鼠肾脏的保护作用  

Effect of O-linked N-acetylglucosamine pathway in the rats acute renal injury induced by cecal ligation and puncture

作　　者：陆新健[1] 王瑾[1] 郑康[1] 景亮[1] 

机构地区：[1]东南大学附属中大医院麻醉科,南京210009

出　　处：《国际麻醉学与复苏杂志》2013年第1期17-20,48,共5页International Journal of Anesthesiology and Resuscitation

摘　　要：目的探讨应用谷氨酰胺（Gln）增加蛋白质氧位N-乙酰葡萄糖胺（O-linked N-acetylglucosamine，O-GlcNAc）修饰对脓毒症大鼠。肾脏保护中的作用。方法雄性SD大鼠，体重180g-240g，完全随机法分为5组：对照组（S组，行开关腹手术，n=12）；脓毒症组[C组，行盲肠结扎穿孔（cecal ligation and puncture，CLP）术，n=16]；Gln治疗组（G组，行CLP术，术后即刻Gln 0．75g／kg微量泵注1h，n=16）；槲皮素＋Gln干预组（Q组，行CLP术，术毕时腹腔注射槲皮素0．4g／kg，继予Gln微量泵注，n=16）；四氧嘧啶＋Gln干预组（A组，行CLP术，术毕时腹腔注射四氧嘧啶90mg／kg后，继予Gln微量泵注，n=16）。维持麻醉并记录CLP术后16h血压。24h测动脉血气分析，血浆肌酐（Cr）、尿液肾损伤分子-1（kidney injury molecule-1，KIM-1）含量，肾组织匀浆热休克蛋白70（HSP70）、O-GlcNAc表达水平。结果CLP术后16h，C组平均动脉压（MAP）下降幅度超过基础值30％，G组、Q组、A组大鼠MAP下降明显，24h动脉血乳酸浓度c组、G组、Q组、A组较s组明显升高（P〈0．05）。CLP术后24h，C组血Cr为（57．4±4．9）mmol／L，尿KIM-1为（66．3±8．8）ng／L，较S组的血Cr（35．7±5．9）mmol／L、尿KIM-1（47．0±3．7）ng／L明显升高，G组血Cr为（42．2±5．4）mmol／L，尿KIM-1为（53．7±3．0）ng／L，较C组明显降低，Q、A两组血Cr分别为（51．4±2．9）、（57．4±2．6）mmol／L，尿KIM-1分别为（70．9±17．7）、（75．3±10．9）ng／L，较G组明显升高，差异均有统计学意义（P〈0．05）。肾组织蛋白质O-GlcNAc修饰水平G组较c组明显升高，A组较G组明显降低（P〈0．05）；肾组织HSP70表达C组较S组明显升高，G组较C组明显升高，Q、A组较G组明显下降（P〈0．05）。结论Gln通过增加细胞蛋白质O-GlcNAc修饰调节炎症反应，减轻脓毒症大鼠的肾损伤。Objective To observe the protection effect of increasing activity of O-linked N-acetylglucosamine （O-GlcNAc） pathway by glutamine treatment in the rats acute renal injury induced by cecal ligation and puncture （CLP）. Methods Seventy six healthy Sprague-Dawley rats were randomly divided into five groups： the CLP group （group C, n=16） receiving CLP, Shamoperation group （group S, n=12）, the glutamine group （group G, n=16） receiving CLP and intravenous injection of 0.75 g/kg glutarnine in 1 h, the quercetin and glutamine treatment group （group Q, n=16 ） receiving peritoneal injection of 0.4 g/kg quercetin before glutamine treatment, the alloxan and glutamine treatment group （group A, n=16） receiving peritoneal injection of 90 mg/kg alloxan before glutamine treatment. All rats were used general anaesthesia and MAP were monitored for 16 h. After 24 h, the survival rats were anesthetized again to draw arterial for gas analysis and Cr, and urine for kidney injury molecule-1 （KIM-1） were detected. The kidney was reserved to detect the expression of O-GlcNAc and HSP70 by Western Blotting after the rats were sacrificed. Results In group S, the MAP was stable, and the lactic acid at 24 h was nomal. In group C, G, Q and A, the MAP were descent obvious at 16 h after CLPI and the lactic acid of those groups increased at the 24th timepoint compared to group S （P〈0.05）. Compared with group S, the Cr（57.4±4.9） mmol/L and KIM-1（66.3-＋8.8） ng/L increased in the group C（P〈0.05）. In group G, the Cr and KIM-1 decressed but the expression of O-GlcNAc and HSP70 were increased compared with group C （P〈0.05）. In group Q and group A, the Cr[（51.4±2.9）, （57.4±2.6） mmol/L] and KIM-1 [（70.9± 17.7 ）, （75.3 ± 10.9） ng/L] increased Compared with group G （P〈0.05）.The expression of O-GlcNAc in the group A, and HSP in the two groups decreased compared with group G （P〈0.05）. Conclusions Glutamine may induces the expression of HSP70 in rats by increasing the

关 键 词：脓毒症 急性肾损伤 谷氨酰胺 氧位N-乙酰葡萄糖胺修饰 

分 类 号：R45[医药卫生—治疗学]