沙苑子总黄酮对糖尿病大鼠降脂及肾保护作用的实验研究
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摘要
目的:探讨沙苑子总黄酮对糖尿病大鼠降脂及肾脏保护作用。方法:采用尾静脉注射30 mg/kg链脲佐菌素(STZ)并给予高脂饲料诱导建立糖尿病模型;实验分为正常组,模型组和沙苑子总黄酮低(40mg/kg)、中(80 mg/kg)、高剂量组(120 mg/kg),阳性对照组(辛伐他汀,15 mg/kg);给药6周后测定各组大鼠体质量、肾脏指数;检测血清TG、TC、SCr、BUN浓度;检测肾脏SOD、CAT、GSH-Px活性和MDA含量;测定血清和肾脏TNF-α、IL-6表达的变化;进行肾脏病理学观察。结果:与正常组相比,模型组大鼠血清TG、TC、SCr、BUN、肾脏MDA水平显著上升(P <0. 01或P <0. 05),血清HDL-C和肾脏SOD水平显著下降(P <0. 01或P <0. 05),血清及肾脏TNF-α、IL-6水平显著上升(P <0. 01或P <0. 05);与模型组相比,各剂量组给药后血清TG、TC、SCr、BUN、肾脏MDA水平逐渐下降,高剂量组差异具统计学意义(P <0. 01或P <0. 05),肾脏SOD水平显著上调(P <0. 01),高剂量组血清及肾脏TNF-α、IL-6水平显著下降(P <0. 01或P <0. 05);各给药组肾组织病理学变化均有改善。结论:沙苑子总黄酮具降血脂作用,并能改善糖尿病引起的肾脏损伤,其机制可能与减轻氧化应激损伤及对炎性细胞因子的调控相关。
Objective:To investigate the hypolipidemic effect and kidney protection of total flavonoids from Astragalus complanatus in diabetes rat models.Methods:Diabetic model was induced by tail vein injection of30 mg/kg streptozotocin(STZ)and high fat diet.All rats was randomly divided into following groups:normal group,model group,positive group(Simvastatin 15 mg·kg~(-1)·d~(-1)),low-dose.medium-dose and highdose group of total flavonoids from Astragalus complanatus(40,80,120 mg·kg~(-1)·d~(-1)),Six weeks later,Body and kidney index was detected after administration.The concentration of serum TG,TC,SCr,BUN and renal tissue SOD,CAT,GSH-Px,MDA were checked,the expression levels of TNF-αand IL-6 both in serum and renal tissue were determined,meanwhile,renal tissue histopathology changes were observed by light microscope.Results:Compared with normal control group,concentration of serum TG,TC,SCr,BUN,level of renal tissue MDA were increased obviously(P<0.01 or P<0.05),renal tissue SOD activity was extremely decreased(P<0.01 or P<0.05),the expression levels of TNF-αand IL-6 both in serum and renal tissue reduced obviously(P<0.01 or P<0.05)in model group.Compared with model group,serum TG,TC,SCr,BUN and renal tissue MDA levels in different dose group were gradually decreased,especially for high-dose group(P<0.01 or P<0.05),in contrast,renal tissue SOD activity was enhanced significantly(P<0.01);at the same time,the expression levels of TNF-αand IL-6 both in serum and renal tissue of high-dose group were obviously reduced(P<0.01 or P<0.05).The renal tissue histopathology changes in each medication group were improved significantly.Conclusion:The total flavonoids from Astragalus complanatus have hypolipidemic effect,which could improve renal injury induced by diabetes.The mechanism of renal protection was probably associated with alleviating oxidative stress damage and regulating inflammatory cytokine release.
Objective:To investigate the hypolipidemic effect and kidney protection of total flavonoids from Astragalus complanatus in diabetes rat models.Methods:Diabetic model was induced by tail vein injection of30 mg/kg streptozotocin(STZ)and high fat diet.All rats was randomly divided into following groups:normal group,model group,positive group(Simvastatin 15 mg·kg~(-1)·d~(-1)),low-dose.medium-dose and highdose group of total flavonoids from Astragalus complanatus(40,80,120 mg·kg~(-1)·d~(-1)),Six weeks later,Body and kidney index was detected after administration.The concentration of serum TG,TC,SCr,BUN and renal tissue SOD,CAT,GSH-Px,MDA were checked,the expression levels of TNF-αand IL-6 both in serum and renal tissue were determined,meanwhile,renal tissue histopathology changes were observed by light microscope.Results:Compared with normal control group,concentration of serum TG,TC,SCr,BUN,level of renal tissue MDA were increased obviously(P<0.01 or P<0.05),renal tissue SOD activity was extremely decreased(P<0.01 or P<0.05),the expression levels of TNF-αand IL-6 both in serum and renal tissue reduced obviously(P<0.01 or P<0.05)in model group.Compared with model group,serum TG,TC,SCr,BUN and renal tissue MDA levels in different dose group were gradually decreased,especially for high-dose group(P<0.01 or P<0.05),in contrast,renal tissue SOD activity was enhanced significantly(P<0.01);at the same time,the expression levels of TNF-αand IL-6 both in serum and renal tissue of high-dose group were obviously reduced(P<0.01 or P<0.05).The renal tissue histopathology changes in each medication group were improved significantly.Conclusion:The total flavonoids from Astragalus complanatus have hypolipidemic effect,which could improve renal injury induced by diabetes.The mechanism of renal protection was probably associated with alleviating oxidative stress damage and regulating inflammatory cytokine release.
引文
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[10]张志坚,吴灿,田黎,等.沙苑子总黄酮对内质网应激诱导的细胞凋亡在百草枯致大鼠肺损伤中的保护作用[J].医学研究生学报,2014,27(8):806-809.
[11]侯燕,冯一中,蒋小岗,等.沙苑子总黄酮对博莱霉素致大鼠肺纤维化的干预作用及其机制研究[J].中国药理学通报,2013,29(1):88-93.
[12]Sham T T,Zhang H,Mok D K W,et al.Chemical analysis of Astragali Complanati semen and its hypocholesterolemic effect using serum metabolomics based on gas chromatography-mass spectrometry[J].Antioxidants,2017,6(3):57.
[13]Zhu J,Zhang H,Zhu Z,et al.Effects and mechanism of flavonoids from Astragalus complanatus on breast cancer growth[J].Naunyn-Schmiedeberg’s Archives of Pharmacology,2015,388(9):965-972.
[14]Han R,Wu W Q,Wu X P,et al.Effect of total flavonoids from the seeds of Astragali complanati,on natural killer cell function[J].Journal of Ethnopharmacology,2015,173:157-165.
[15]Wong J H,Cho S W S,Ng T B,et al.Apoptosis and anti-cancer drug discovery:the power of medicinal fungi and plants[J].Current Medicinal Chemistry,2017,25(40):5613-5630.
[16]Zhang H W,Lin Z X,Xu C,et al.Astragalus(a traditional Chinese medicine)for treating chronic kidney disease[J].The Cochrane Library,2014,10(22):101-116.
[17]Pistrosch F,Furashova O,Engelmann K,et al.Microvascular Complications of Diabetes:Nephropathy,Retinopathy,and Maculopathy[J].Diabetes Stoffwechsel and Herz,2018,27(1):24-32.
[18]LIU Shuwei.Protective mechanism of Eplerenone on rats with diabetic nephropathy[J].Chin J Mod Appl Pharm(中国现代应用药学),2018,35(6):812-815
[19]Ebert T,Halbritter J.Epidemiology and pathogenesis of diabetic kidney disease[J].Diabetologe,2018,14(2):78-85.
[20]Ruan X Z,Varghese Z,Moorhead J F.An update on the lipid nephrotoxicity hypothesis.[J].Nature Reviews Nephrology,2009,5(12):713-721.
[21]卢岚,黄梦璇,朱昭章.慢性肾脏病与脂质紊乱的相关性研究[J].检验医学与临床,2015,12(6)734-736.
[22]龙凯,朱昭章,卢岚,等.慢性肾脏病3、4期患者脂代谢紊乱相关因素分析[J].山东医药,2013,53(48):16-18.
[23]Vaziri,N.D.Dyslipidemia of chronic renal failure:the nature,mechanisms,and potential consequences[J].A-merican Journal of Physiology-Renal Physiology,2006,290(2):F262-F272.
[24]Tong L,Adler S G.Diabetic kidney disease[J].Clinical Journal of the American Society of Nephrology,2018,13(2):335-338.
[25]Lovisa S,Le Bleu V S,Tampe B,et al.Epithelial-tomesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosi[J].Nature medicine,2015,21(9):998.
[26]Williams V R,Scholey J W.Angiotensin-converting enzyme 2 and renal disease[J].Current Opinion in Nephrology and Hypertension,2018,27(1):35-41.
[27]Aghadavod E,Khodadadi S,Baradaran A,et al.Role of oxidative stress and inflammatory factors in diabetic kidney disease[J].Iranian Journal of Kidney Diseases,2016,10(6):337-343.
[28]陈小永,宋军营,王自闯.炎症和氧化应激在糖尿病肾病中的作用[J].中国老年学杂志,2017,37(24):6254-6256.
[29]Juan F.Navarro-González,Jarque A,Muros M,et al.Tumor necrosis factor-αas a therapeutic target for diabetic nephropathy[J].Cytokine Growth Factor Rev,2009,20(2):0-173.
[30]Navarro-Gonzalez J F,Mora-Fernandez C.The Role of inflammatory cytokines in diabetic nephropathy[J].Journal of the American Society of Nephrology,2008,19(3):433-442.
[31]Cao Q,Harris D C H,Wang Y.Macrophages in kidney injury,inflammation,and fibrosis[J].Physiology,2015,30(3):183-194.
[32]秦文敬.糖尿病肾病患者与相关细胞因子水平的变化[J].放射免疫学杂志,2005,18(3):190-191.
[2]Roy S S,Shah P H.Lipid profile in diabetes mellitus[J].National Journal of Integrated Research in Medicine,2018,7(4):8-13.
[3]唐慎微.重修政和经史证类备用本草(下)[M].北京:中国中医药出版社,2013:450-451.
[4]许梦莹,郭日新,张晓,等.沙苑子化学成分研究[J].中国中药杂志,2018,43(7):1459-1466.
[5]崔宝良,陆蕴茹,魏璐雪.沙苑子化学成分研究[J].药学学报,1989,24(3):189-193.
[6]吴晓,刘银芳,刘春宇.沙苑子化学成分研究[J].安徽中医药大学学报,2014,33(3):91-94.
[7]陈妙华,刘风山.沙苑子化学成分的研究Ⅱ[J].药学学报,1988,23(3):218.
[8]张清安,范学辉,刘梅,等.沙苑子黄酮类化合物的响应面法优化提取及其清除DPPH自由基能力[J].天然产物研究与开发,2013,15(10):1339-1345.
[9]欧丽娜,张建军,高晶,等.沙苑子总黄酮对高脂大鼠的降甘油三酯作用及对肝脏DGAT2与ATGL的影响[J].中华中医药杂志,2015,30(3):898-901.
[10]张志坚,吴灿,田黎,等.沙苑子总黄酮对内质网应激诱导的细胞凋亡在百草枯致大鼠肺损伤中的保护作用[J].医学研究生学报,2014,27(8):806-809.
[11]侯燕,冯一中,蒋小岗,等.沙苑子总黄酮对博莱霉素致大鼠肺纤维化的干预作用及其机制研究[J].中国药理学通报,2013,29(1):88-93.
[12]Sham T T,Zhang H,Mok D K W,et al.Chemical analysis of Astragali Complanati semen and its hypocholesterolemic effect using serum metabolomics based on gas chromatography-mass spectrometry[J].Antioxidants,2017,6(3):57.
[13]Zhu J,Zhang H,Zhu Z,et al.Effects and mechanism of flavonoids from Astragalus complanatus on breast cancer growth[J].Naunyn-Schmiedeberg’s Archives of Pharmacology,2015,388(9):965-972.
[14]Han R,Wu W Q,Wu X P,et al.Effect of total flavonoids from the seeds of Astragali complanati,on natural killer cell function[J].Journal of Ethnopharmacology,2015,173:157-165.
[15]Wong J H,Cho S W S,Ng T B,et al.Apoptosis and anti-cancer drug discovery:the power of medicinal fungi and plants[J].Current Medicinal Chemistry,2017,25(40):5613-5630.
[16]Zhang H W,Lin Z X,Xu C,et al.Astragalus(a traditional Chinese medicine)for treating chronic kidney disease[J].The Cochrane Library,2014,10(22):101-116.
[17]Pistrosch F,Furashova O,Engelmann K,et al.Microvascular Complications of Diabetes:Nephropathy,Retinopathy,and Maculopathy[J].Diabetes Stoffwechsel and Herz,2018,27(1):24-32.
[18]LIU Shuwei.Protective mechanism of Eplerenone on rats with diabetic nephropathy[J].Chin J Mod Appl Pharm(中国现代应用药学),2018,35(6):812-815
[19]Ebert T,Halbritter J.Epidemiology and pathogenesis of diabetic kidney disease[J].Diabetologe,2018,14(2):78-85.
[20]Ruan X Z,Varghese Z,Moorhead J F.An update on the lipid nephrotoxicity hypothesis.[J].Nature Reviews Nephrology,2009,5(12):713-721.
[21]卢岚,黄梦璇,朱昭章.慢性肾脏病与脂质紊乱的相关性研究[J].检验医学与临床,2015,12(6)734-736.
[22]龙凯,朱昭章,卢岚,等.慢性肾脏病3、4期患者脂代谢紊乱相关因素分析[J].山东医药,2013,53(48):16-18.
[23]Vaziri,N.D.Dyslipidemia of chronic renal failure:the nature,mechanisms,and potential consequences[J].A-merican Journal of Physiology-Renal Physiology,2006,290(2):F262-F272.
[24]Tong L,Adler S G.Diabetic kidney disease[J].Clinical Journal of the American Society of Nephrology,2018,13(2):335-338.
[25]Lovisa S,Le Bleu V S,Tampe B,et al.Epithelial-tomesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosi[J].Nature medicine,2015,21(9):998.
[26]Williams V R,Scholey J W.Angiotensin-converting enzyme 2 and renal disease[J].Current Opinion in Nephrology and Hypertension,2018,27(1):35-41.
[27]Aghadavod E,Khodadadi S,Baradaran A,et al.Role of oxidative stress and inflammatory factors in diabetic kidney disease[J].Iranian Journal of Kidney Diseases,2016,10(6):337-343.
[28]陈小永,宋军营,王自闯.炎症和氧化应激在糖尿病肾病中的作用[J].中国老年学杂志,2017,37(24):6254-6256.
[29]Juan F.Navarro-González,Jarque A,Muros M,et al.Tumor necrosis factor-αas a therapeutic target for diabetic nephropathy[J].Cytokine Growth Factor Rev,2009,20(2):0-173.
[30]Navarro-Gonzalez J F,Mora-Fernandez C.The Role of inflammatory cytokines in diabetic nephropathy[J].Journal of the American Society of Nephrology,2008,19(3):433-442.
[31]Cao Q,Harris D C H,Wang Y.Macrophages in kidney injury,inflammation,and fibrosis[J].Physiology,2015,30(3):183-194.
[32]秦文敬.糖尿病肾病患者与相关细胞因子水平的变化[J].放射免疫学杂志,2005,18(3):190-191.