大黄素对高脂饮食小鼠肾皮质氧化应激的影响
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摘要
目的探究大黄素对高脂饮食小鼠肾皮质氧化应激的影响。方法利用高脂饮食喂养C57BL/6J小鼠,制造高脂饮食模型,并给予大黄素或吡格列酮处理。根据饮食及治疗不同,分为:普通饮食组、高脂饮食组、低剂量大黄素处理组、高剂量大黄素处理组和吡格列酮对照组。实验结束后,取血样检测空腹血糖和空腹胰岛素,取尿样检测尿蛋白排泄率,取小鼠肾皮质专用试剂盒检测肾皮质细胞ROS和MDA含量以及SOD活力。Western blotting检测PPAR-γ水平。结果与普通饮食组小鼠相比,高脂饮食组小鼠空腹血糖、空腹胰岛素和尿蛋白排泄率增加,肾皮质的ROS和MDA含量增加,SOD活力下降,PPAR-γ表达量减少,差异有统计学意义(P<0.05)。与高脂饮食组小鼠相比,低剂量处理组空腹胰岛素,24 h尿蛋白排泄率,和MDA水平下降,差异具有统计学意义(P<0.05);高剂量大黄素处理组和吡格列酮处理组小鼠空腹血糖、空腹胰岛素和尿蛋白排泄率降低,肾皮质的ROS和MDA含量减少,SOD活力增强,PPAR-γ表达量增加,差异有统计学意义(P<0.05)。结论大黄素可改善高脂饮食小鼠肾皮质的氧化应激。
Objective To investigate the effects of emodin(EM) on the oxidative stress of kidney in high fat diet-induced mice with obesity. Methods Healthy male C57 BL/6 J mice were fed with high fat diet(HFD) to induce the model. The mice were divided into NC group(common diet),HFD group,low dose EM(L-EM) group,high dose EM(H-EM) group,and pioglitazone(PI) group according to different diet and treatment. The fasting plasma glucose,the fasting serum insulin and the urine creatinine were measured.ROS,MDA,SOD in renal cortex were detected by specified kits. PPAR-γ in the kidney cortex was detected by Western blotting.Results Compared to NC group,fasting plasma glucose,fasting serum insulin,urine creatinine,ROS and MDA levels increased significantly,as well as SOD activity and PPAR-γ levels decreased in HFD group(P< 0.05). However,compared to HFD group,fasting serum insulin,urine creatinine and MDA were down-regulated in low dose emodin group(P< 0.05),while fasting plasma glucose,fasting serum insulin,urine creatinine,ROS and MDA levels decreased,and SOD activity and PPAR-γ level increased in high dose emodin group and pioglitazone group(P< 0.05). Conclusion Emodin may alleviate the oxidative stress of kidney in high fat diet-induced obese mice.
Objective To investigate the effects of emodin(EM) on the oxidative stress of kidney in high fat diet-induced mice with obesity. Methods Healthy male C57 BL/6 J mice were fed with high fat diet(HFD) to induce the model. The mice were divided into NC group(common diet),HFD group,low dose EM(L-EM) group,high dose EM(H-EM) group,and pioglitazone(PI) group according to different diet and treatment. The fasting plasma glucose,the fasting serum insulin and the urine creatinine were measured.ROS,MDA,SOD in renal cortex were detected by specified kits. PPAR-γ in the kidney cortex was detected by Western blotting.Results Compared to NC group,fasting plasma glucose,fasting serum insulin,urine creatinine,ROS and MDA levels increased significantly,as well as SOD activity and PPAR-γ levels decreased in HFD group(P< 0.05). However,compared to HFD group,fasting serum insulin,urine creatinine and MDA were down-regulated in low dose emodin group(P< 0.05),while fasting plasma glucose,fasting serum insulin,urine creatinine,ROS and MDA levels decreased,and SOD activity and PPAR-γ level increased in high dose emodin group and pioglitazone group(P< 0.05). Conclusion Emodin may alleviate the oxidative stress of kidney in high fat diet-induced obese mice.
引文
[1] Abarca-Gómez L,Abdeen ZA,Hamid ZA,et al. Worldwide trends in body-mass index,underweight,overweight,and obesity from1975 to 2016:a pooled analysis of 2416 population-based measurement studies in 128. 9 million children,adolescents,and adults[J]. Lancet,2017,390(10113):2627-2642.
[2] Ogden CL,Carroll MD,Kit BK,et al. Prevalence of childhood and adult obesity in the United States,2011-2012[J]. JAMA,2014,311(8):806-814.
[3] Nehus E. Obesity and chronic kidney disease[J]. Curr Opin Pediatr,2018,30(2):241-246.
[4] Wang D,Luo Y,Wang X,et al. The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents renal and liver disease in western diet induced obesity mice[J]. Int J Mol Sci,2018,19(1):pii:E137.
[5] Zuo L,Best TM,Roberts WJ,et al. Characterization of reactive oxygen species in diaphragm[J]. Acta Physiol(Oxf),2015,213(3):700-710.
[6] Chen H,Huang RS,Yu XX,et al. Emodin protects against oxidative stress and apoptosis in HK-2 renal tubular epithelial cells after hypoxia/reoxygenation[J]. Exp Ther Med,2017,14(1):447-452.
[7]宋冰,刘学政.大黄素对2型糖尿病小鼠血糖、胰岛素水平的影响及机制探讨[J].山东医药,2011,51(38):32-33.
[8] Jing D,Bai H,Yin S. Renoprotective effects of emodin against diabetic nephropathy in rat models are mediated via PI3K/Akt/GSK-3βand Bax/caspase-3 signaling pathways[J]. Exp Ther Med,2017,14(5):5163-5169.
[9]孙耀,于亚丽,李江,等.大黄素对高脂饮食诱导的肥胖小鼠肾脏损害的保护作用[J].中华内分泌与代谢病杂志,2018,11(34):946-950.
[10] Chen Z,Zhang L,Yi J,et al. Promotion of adiponectin multimerization by emodin:A novel AMPK activator with PPARγ-agonist activity[J]. J Cell Biochem,2012,113(11):3547-3558.
[11]孙耀,贾云宏.硫化氢减轻糖尿病小鼠胰岛素抵抗的作用机制研究[J].中国现代医学杂志,2017,27(9):13-18.
[12] Xue J,Ding W,Liu Y. Anti-diabetic effects of emodin involved in the activation of PPAR gamma on high-fat diet-fed and low dose of streptozotocin-induced diabetic mice[J]. Fitoterapia,2010,81(3):173-177.
[13] Zhang X,Zhang R,Lv P,et al. Emodin up-regulates glucose metabolism,decreases lipolysis,and attenuates inflammation in vitro[J]. J Diabetes,2015,7(3):360-368.
[14] Song P,Kim JH,Ghim J,et al. Emodin regulates glucose utilization by activating AMP-activated protein kinase[J]. J Biol Chem,2013,288(8):5732-5742.
[2] Ogden CL,Carroll MD,Kit BK,et al. Prevalence of childhood and adult obesity in the United States,2011-2012[J]. JAMA,2014,311(8):806-814.
[3] Nehus E. Obesity and chronic kidney disease[J]. Curr Opin Pediatr,2018,30(2):241-246.
[4] Wang D,Luo Y,Wang X,et al. The sodium-glucose cotransporter 2 inhibitor dapagliflozin prevents renal and liver disease in western diet induced obesity mice[J]. Int J Mol Sci,2018,19(1):pii:E137.
[5] Zuo L,Best TM,Roberts WJ,et al. Characterization of reactive oxygen species in diaphragm[J]. Acta Physiol(Oxf),2015,213(3):700-710.
[6] Chen H,Huang RS,Yu XX,et al. Emodin protects against oxidative stress and apoptosis in HK-2 renal tubular epithelial cells after hypoxia/reoxygenation[J]. Exp Ther Med,2017,14(1):447-452.
[7]宋冰,刘学政.大黄素对2型糖尿病小鼠血糖、胰岛素水平的影响及机制探讨[J].山东医药,2011,51(38):32-33.
[8] Jing D,Bai H,Yin S. Renoprotective effects of emodin against diabetic nephropathy in rat models are mediated via PI3K/Akt/GSK-3βand Bax/caspase-3 signaling pathways[J]. Exp Ther Med,2017,14(5):5163-5169.
[9]孙耀,于亚丽,李江,等.大黄素对高脂饮食诱导的肥胖小鼠肾脏损害的保护作用[J].中华内分泌与代谢病杂志,2018,11(34):946-950.
[10] Chen Z,Zhang L,Yi J,et al. Promotion of adiponectin multimerization by emodin:A novel AMPK activator with PPARγ-agonist activity[J]. J Cell Biochem,2012,113(11):3547-3558.
[11]孙耀,贾云宏.硫化氢减轻糖尿病小鼠胰岛素抵抗的作用机制研究[J].中国现代医学杂志,2017,27(9):13-18.
[12] Xue J,Ding W,Liu Y. Anti-diabetic effects of emodin involved in the activation of PPAR gamma on high-fat diet-fed and low dose of streptozotocin-induced diabetic mice[J]. Fitoterapia,2010,81(3):173-177.
[13] Zhang X,Zhang R,Lv P,et al. Emodin up-regulates glucose metabolism,decreases lipolysis,and attenuates inflammation in vitro[J]. J Diabetes,2015,7(3):360-368.
[14] Song P,Kim JH,Ghim J,et al. Emodin regulates glucose utilization by activating AMP-activated protein kinase[J]. J Biol Chem,2013,288(8):5732-5742.