番泻苷A对STZ诱导的糖尿病肾病大鼠肾损伤和炎症反应的调节作用
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摘要
目的探索番泻苷A(Sennoside A,SA)对链脲佐菌素(Streptozocin,STZ)诱导的糖尿病肾病大鼠肾损伤和炎症反应的影响。方法 40只大鼠随机分为4组:对照组(Control组)、番泻苷A对照组(SA组)、糖尿病肾病模型组(STZ组)和番泻苷A处理组(STZ+SA组)。应用全自动生化分析仪检测尿蛋白、血清肌酸酐和尿素氮。蛋白印记检测Caspase-3、Caspase-9表达。脱氧核糖核苷酸末端转移酶介导的缺口末端标记(Terminal deoxynucleotidyl transferase-mediated d UTP nick labeling,TUNEL)染色检测肾脏组织细胞凋亡。酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)检测白细胞介素(Interleukin,IL)-1β和IL-18水平。免疫组织化学染色检测肾脏组织纤连蛋白(Fibronectin,FN)表达。结果 STZ组大鼠尿蛋白、血清肌酐、尿素氮、IL-β、IL-18水平,Caspase-3、Caspase-9、Fibronectin表达,以及大鼠肾脏组织细胞凋亡率均高于对照组、STZ+SA组(P <0.01)。结论番泻苷A可减轻STZ诱导的糖尿病肾病大鼠肾损伤和炎症反应。
Objective To explore the effect of sennoside A on the renal injury and inflammation in STZ-induced diabetic nephropathy rats.Methods Totally 40 rats were randomly divided into four groups: control group, sennoside A control group(SA group),diabetic nephropathy model group(STZ group) and sennoside A treatment group(STZ + SA group).The levels of proteinuria, serum creatinine and urea nitrogen were measured by fully automatic biochemical analyser; the apoptosis of renal tissue was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick labeling(TUNEL); the expression of Caspase-3 and Caspase-9 was tested by Western blot; the levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA).The expression of fibronectin in kidney tissue was measured by immunohistochemical staining.Results The levels of proteinuria, serum creatinine,urea nitrogen,IL-1β and IL-18, the expression of Caspase-3,Caspase-9 and fibronectinin,and the apoptosis rate of renal tissue cells in STZ group were higher than those of control group and STZ + SA group(P < 0.01).Conclusion Sennoside A can relieve the renal injury and inflammation in STZ-induced diabetic nephropathy rats.
Objective To explore the effect of sennoside A on the renal injury and inflammation in STZ-induced diabetic nephropathy rats.Methods Totally 40 rats were randomly divided into four groups: control group, sennoside A control group(SA group),diabetic nephropathy model group(STZ group) and sennoside A treatment group(STZ + SA group).The levels of proteinuria, serum creatinine and urea nitrogen were measured by fully automatic biochemical analyser; the apoptosis of renal tissue was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick labeling(TUNEL); the expression of Caspase-3 and Caspase-9 was tested by Western blot; the levels of IL-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA).The expression of fibronectin in kidney tissue was measured by immunohistochemical staining.Results The levels of proteinuria, serum creatinine,urea nitrogen,IL-1β and IL-18, the expression of Caspase-3,Caspase-9 and fibronectinin,and the apoptosis rate of renal tissue cells in STZ group were higher than those of control group and STZ + SA group(P < 0.01).Conclusion Sennoside A can relieve the renal injury and inflammation in STZ-induced diabetic nephropathy rats.
引文
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[17]Ali BH,Al-Salam S,Al HIS,et al.Abrogation of cisplatin-induced nephrotoxicity by emodin in rats[J].Fundam Clin Pharmacol,2013,27(2):192-200.
[18]Meng Z,Yan Y,Tang Z,et al.Anti-hyperuricemic and nephroprotective effects of rhein in hyperuricemic mice[J].Planta Med,2015,81(4):279-285.
[19]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.
[20]Guan Y,Wu XX,Duan JL,et al.Effects and mechanism of combination of rhein and danshensu in the treatment of chronic kidney disease[J].Am J Chin Med,2015,43(7):1381-1400.
[21]Zhang ZH,Vaziri ND,Wei F,et al.An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure[J].Sci Rep,2016,6:22151.
[22]Zhang Q,Yin S,Liu L,et al.Rhein reversal of DNA hypermethylationassociated klotho suppression ameliorates renal fibrosis in mice[J].Sci Rep,2016,6:34597.
[23]Gao J,Wang F,Wang W,et al.Emodin suppresses hyperglycemiainduced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP[J].PLoS One,2014,9(4):e93588.
[2]Donate-Correa J,Martín-Núˇnez E,Muros-de-Fuentes M,et al.Inflammatory cytokines in diabetic nephropathy[J].J Diabetes Res,2015:948417.
[3]McKnight AJ,Duffy S,Maxwell AP.Genetics of diabetic nephropathy:a long road of discovery[J].Curr Diab Rep,2015,15(7):41.
[4]Tu X,Ye X,Xie C,et al.Combination therapy with Chinese medicine and ACEI/ARB for the management of diabetic nephropathy:the promise in research fragments[J].Curr Vasc Pharmacol,2015,13(4):526-559.
[5]Sun GD,Li CY,Cui WP,et al.Review of herbal traditional Chinese medicine for the treatment of diabetic nephropathy[J].J Diabetes Res,2016:5749857.
[6]Zhang Z,Rui W,Wang ZC,et al.Anti-proliferation and antimetastasis effect of barbaloin in non-small cell lung cancer via inactivating p38MAPK/CDC25B/HSP27 pathway[J].Oncol Rep,2017,38(2):1172-1180.
[7]Esposito F,Carli I,Del VC,et al.Sennoside A,derived from the traditional Chinese medicine plant Rheum L.,is a new dual HIV-1 inhibitor effective on HIV-1 replication[J].Phytomedicine,2016,23(12):1383-1391.
[8]Hwang IY,Jeong CS.Gastroprotective activities of Sennoside A and Sennoside B via the up-regulation of prostaglandin E2and the inhibition of H(+)/K(+)-ATPase[J].Biomol Ther(Seoul),2015,23(5):458-464.
[9]Hajhosseiny R,Khavandi K,Jivraj N,et al.Have we reached the limits for the treatment of diabetic nephropathy[J].Expert Opin Investig Drugs,2014,23(4):511-522.
[10]Wang ZS,Xiong F,Xie XH,et al.Astragaloside IV attenuates proteinuria in streptozotocin-induced diabetic nephropathy via the inhibition of endoplasmic reticulum stress[J].BMC Nephrol,2015,16:44.
[11]Teschke R,Zhang L,Long H,et al.Traditional Chinese medicine and herbal hepatotoxicity:a tabular compilation of reported cases[J].Ann Hepatol,2015,14(1):7-19.
[12]Gao D,Zeng LN,Zhang P,et al.Rhubarb anthraquinones protect rats against mercuric chloride(hgcl(2))-induced acute renal failure[J].Molecules(Basel,Switzerland),2016,21(3):298.
[13]Chen X,Peng S,Zeng H,et al.Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy[J].Indian J Pharmacol,2015,47(1):27-33.
[14]Zhang Q,Liu L,Lin W,et al.Rhein reverses Klotho repression via promoter demethylation and protects against kidney and bone injuries in mice with chronic kidney disease[J].Kidney Int,2017,91(1):144-156.
[15]Lian Y,Xie L,Chen M,et al.Effects of an astragalus polysaccharide and rhein combination on apoptosis in rats with chronic renal failure[J].Evid Based Complement Alternat Med,2014:271862.
[16]Zhao Y,Fang Y,Zhao H,et al.Chrysophanol inhibits endoplasmic reticulum stress in cerebral ischemia and reperfusion mice[J].Eur J Pharmacol,2018,818:1-9.
[17]Ali BH,Al-Salam S,Al HIS,et al.Abrogation of cisplatin-induced nephrotoxicity by emodin in rats[J].Fundam Clin Pharmacol,2013,27(2):192-200.
[18]Meng Z,Yan Y,Tang Z,et al.Anti-hyperuricemic and nephroprotective effects of rhein in hyperuricemic mice[J].Planta Med,2015,81(4):279-285.
[19]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.
[20]Guan Y,Wu XX,Duan JL,et al.Effects and mechanism of combination of rhein and danshensu in the treatment of chronic kidney disease[J].Am J Chin Med,2015,43(7):1381-1400.
[21]Zhang ZH,Vaziri ND,Wei F,et al.An integrated lipidomics and metabolomics reveal nephroprotective effect and biochemical mechanism of Rheum officinale in chronic renal failure[J].Sci Rep,2016,6:22151.
[22]Zhang Q,Yin S,Liu L,et al.Rhein reversal of DNA hypermethylationassociated klotho suppression ameliorates renal fibrosis in mice[J].Sci Rep,2016,6:34597.
[23]Gao J,Wang F,Wang W,et al.Emodin suppresses hyperglycemiainduced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP[J].PLoS One,2014,9(4):e93588.