富硒木耳水提物对链脲佐菌素诱导的小鼠糖尿病肾损伤的保护作用
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摘要
目的研究富硒木耳水提物(aqueous of Se-enriched Auricularia auricular,AESAA)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾损伤的保护作用及机制。方法给予小鼠高脂饮食联合STZ (80 mg·kg~(-1))建立糖尿病肾病(diabetic nephropathy,DN)模型。将60只C57B/6J小鼠随机分为空白组、模型组、二甲双胍组(metformin,Met,400 mg·kg~(-1))、AESAA低剂量组(500 mg·kg~(-1))、AESAA高剂量组(1 000 mg·kg~(-1))、普通木耳水提物组(aqueous extracts of Auricularia auricular,AEAA,1 000 mg·kg~(-1)),灌胃给药8周后,取血及肾脏组织。检测小鼠血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C)、尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)及尿酸(uric acid,UA)的含量;HE染色评价肾脏组织病理学变化;Western blot检测肾脏组织中高迁移率族蛋白1(high mobility group box 1 protein,HMGB1)、晚期糖基化终产物受体(the receptor of advanced glycation end products,RAGE)和核因子-κB(NF-κB)磷酸化的表达。结果与模型组相比,AESAA能改善肾脏病理性损伤;降低血清中TC、TG、LDL-C、Cr、BUN的含量(P<0.01)和UA的含量(P<0.05);抑制肾组织HMGB1、RAGE蛋白表达(P<0.01)和p-NF-κB蛋白表达(P<0.05)。结论 AESAA能逆转STZ诱导的糖尿病肾损伤,其机制可能与其调控HMGB1/RAGE/NF-κB信号通路有关。
Objective To investigate the protective effects and the underlying mechanism of aqueous extracts of Se-enriched Auricularia auricular(AESAA) on streptozotocin(STZ)-induced diabetic nephropathy in mice.Methods The diabetic mice were induced by a single injection of STZ(80 mg·kg~(-1)) together with high-fat diet.The mice were randomly divided into six groups of 10 animals each:(1) control group,(2) model group,(3) positive:metformin(Met) + STZ,(4) and(5) treatment:low or high dose AESAA treatment group + STZ,(6) AEAA + STZ.The drugs were administered intragastrically once daily for 8 weeks.After 8 weeks,all of the mice were sacrificed,and then the blood and kidney were collected.The biochemical parameters in serum such as TC,TG,LDL-C,Cr,BUN and UA were measured by kits.The pathological conditions of kidney tissues were evaluated by Hematoxylin-eosin staining.The expressions of HMGB1,RAGE and p-NF-κB in kidney tissues were determined by western blot.Results Compared with the model group,AESAA alleviated the pathological damage of kidney tissues,significantly reduced the levels of TC,TG,LDL-C,Cr,BUN(P<0.01) and UA(P<0.05).It also down-regulated the protein expression of HMGB1,RAGE(P<0.01) and p-NF-κB(P<0.05).Conclusion AESAA could reverse STZ-induced kidney injury in mice,and the protective effects might work through the HMGB1/RAGE/NF-κB signaling pathway.
Objective To investigate the protective effects and the underlying mechanism of aqueous extracts of Se-enriched Auricularia auricular(AESAA) on streptozotocin(STZ)-induced diabetic nephropathy in mice.Methods The diabetic mice were induced by a single injection of STZ(80 mg·kg~(-1)) together with high-fat diet.The mice were randomly divided into six groups of 10 animals each:(1) control group,(2) model group,(3) positive:metformin(Met) + STZ,(4) and(5) treatment:low or high dose AESAA treatment group + STZ,(6) AEAA + STZ.The drugs were administered intragastrically once daily for 8 weeks.After 8 weeks,all of the mice were sacrificed,and then the blood and kidney were collected.The biochemical parameters in serum such as TC,TG,LDL-C,Cr,BUN and UA were measured by kits.The pathological conditions of kidney tissues were evaluated by Hematoxylin-eosin staining.The expressions of HMGB1,RAGE and p-NF-κB in kidney tissues were determined by western blot.Results Compared with the model group,AESAA alleviated the pathological damage of kidney tissues,significantly reduced the levels of TC,TG,LDL-C,Cr,BUN(P<0.01) and UA(P<0.05).It also down-regulated the protein expression of HMGB1,RAGE(P<0.01) and p-NF-κB(P<0.05).Conclusion AESAA could reverse STZ-induced kidney injury in mice,and the protective effects might work through the HMGB1/RAGE/NF-κB signaling pathway.
引文
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[8] 王俊,任美萍,陈斯玮,等.龙眼核原花青素提取物对Ⅱ型糖尿病小鼠血糖血脂的影响[J].沈阳药科大学学报,2017,34(7):594-599.
[9] STANCAKOVA A,KUULASMAA T,KUUSISTO J,et al.Genetic risk scores in the prediction of plasma glucose,impaired insulin secretion,insulin resistance and incident type 2 diabetes in the METSIM study [J].Diabetologia,2017,60(9):1722-1730.
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[11] CHENG M,LIU H,ZHANG D,et al.HMGB1 enhances the AGE-induced expression of CTGF and TGF-β via RAGE-dependent signaling in renal tubular epithelial cells[J].Am J Nephrol,2015,41(3):257-66.
[12] 康伟,徐燕颖.地黄多糖对糖尿病肾病大鼠模型的治疗作用及对RAGE/NF-κB信号通路的影响[J].天津中医药,2015,32(6):364-367.
[2] SIFUENTES-FRANCO S,PADILLA-TEJEDA D E,CARRILLO-IBARRA S,et al.Oxidative stress,apoptosis,and mitochondrial function in diabetic nephropathy[J].Int J Endocrinol,2018,2018(2):1-13.
[3] 张敏,姜涛,宋秀霞.波动性高血糖与糖尿病肾病关系的研究[J].山东医药,2010,50(8):71-72.
[4] ROMAN M,JITAUR P,BARBANTE C.Selenium biochemistry and its role for human health[J].Metallomics,2014,6(1):25-54.
[5] 王晶晶,孟繁磊,魏春雁.硒的药理作用及作用机制研究进展[J].沈阳药科大学学报,2018,35(12):1076-1083.
[6] 赵长峰,王惠敏,张俊黎,等.2型糖尿病患者血清微量元素、血糖及体成分相关性分析[J].卫生研究,2008,37(5):600-605.
[7] 陈宁,张影坤,覃妮,等.吊竹梅水提物对糖尿病肾损伤小鼠的肾保护作用[J].中国临床药理学杂志,2017,33(2):131-135.
[8] 王俊,任美萍,陈斯玮,等.龙眼核原花青素提取物对Ⅱ型糖尿病小鼠血糖血脂的影响[J].沈阳药科大学学报,2017,34(7):594-599.
[9] STANCAKOVA A,KUULASMAA T,KUUSISTO J,et al.Genetic risk scores in the prediction of plasma glucose,impaired insulin secretion,insulin resistance and incident type 2 diabetes in the METSIM study [J].Diabetologia,2017,60(9):1722-1730.
[10] SOURRIS K C,MORLEY A L,KOITKA A,et al.Receptor for AGEs (RAGE) blockade may exert its renoprotective effects in patients with diabetic nephropathy via induction of the angiotensin II type 2 (AT2) receptor[J].Diabetologia,2010,53(11):2442-2451.
[11] CHENG M,LIU H,ZHANG D,et al.HMGB1 enhances the AGE-induced expression of CTGF and TGF-β via RAGE-dependent signaling in renal tubular epithelial cells[J].Am J Nephrol,2015,41(3):257-66.
[12] 康伟,徐燕颖.地黄多糖对糖尿病肾病大鼠模型的治疗作用及对RAGE/NF-κB信号通路的影响[J].天津中医药,2015,32(6):364-367.