青风藤提取物对糖尿病肾病大鼠的保护作用及对ANGPTL-4表达的影响
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摘要
目的:探究青风藤(CS)提取物对糖尿病肾病(diabetic nephropathy,DN)大鼠的保护作用及对血管生成素样蛋白-4 (ANGPTL-4)表达水平的影响。方法:将大鼠分为假手术组、模型组、阿托伐他汀组、CS提取物低、中、高剂量组;全自动生化分析仪检测大鼠血清中空腹血糖(FBG)、尿蛋白、血肌酐(Scr)、尿素氮(BUN)含量;用酶联免疫吸附法(ELISA)检测大鼠血清中白细胞介素-6 (IL-6)、白细胞介素-8 (IL-8)、肿瘤坏死因子-α(TNF-α)含量;重量法测定大鼠肾指数; HE染色检测肾组织病理学改变;蛋白免疫印迹(WB)检测肾组织中ANGPTL-4表达情况。结果:CS提取物中、高剂量组FBG、尿蛋白、Scr、BUN、IL-6、IL-8、TNF-α、肾指数及肾组织中ANGPTL-4表达水平显著低于阿托伐他汀组和模型组(P<0. 05);随CS提取物剂量增加,FBG、尿蛋白、Scr、BUN、IL-6、IL-8、TNF-α、肾指数及肾组织中ANGPTL-4表达水平显著降低(P<0. 05),呈剂量依赖性。结论:CS提取物能够降低肾组织中ANGPTL-4表达水平,对DN大鼠肾脏具有保护作用,为DN的临床治疗提供一定的理论基础。
Objective: To explore the protective effect of Caulis Sinomenii(CS) Extract for diabetic nephropathy(diabetic nephropathy,DN) rats and its influence on the expression level of angiopoietin-like protein-4(ANGPTL-4). Methods: The rats were divided into sham operation group,model group,Atorvastatin group and CS extract low,medium and high dose group.The serum fasting blood glucose(FBG),urine protein,serum creatinine(Scr) and urea nitrogen(BUN) contents of rats was detected by automatic biochemical analyzer. The serum interleukin-6(IL-6),interleukin-8(IL-8) and tumor necrosis factor-α(TNF-α) contents of rats were detected by enzyme-linked immunosorbent assay(ELISA). The kidney index of rats was measured by gravimetric method. The pathological changes of renal tissue were detected by HE staining. The expression of ANGPTL-4in renal tissue was detected by protein immunoblotting(WB). Results: The FBG,urinary protein,Scr,BUN,IL-6,IL-8,TNF-α,renal index and ANGPTL-4expression level in renal tissue of the medium and the high dose CS extract groups were significantly lower than those of the Atorvastatin group and the model group(P < 0. 05),with the increased of CS extract dose,the FBG,urine protein,Scr,BUN,IL-6,IL-8,TNF-α,renal index and ANGPTL-4expression level in renal tissue were significantly decreased(P<0. 05),in a dose-dependent manner. Conclusion: CS extract can reduce the expression level of ANGPTL-4in renal tissue and protect the kidney of DN rats,which provides a theoretical basis for the clinical treatment of DN.
Objective: To explore the protective effect of Caulis Sinomenii(CS) Extract for diabetic nephropathy(diabetic nephropathy,DN) rats and its influence on the expression level of angiopoietin-like protein-4(ANGPTL-4). Methods: The rats were divided into sham operation group,model group,Atorvastatin group and CS extract low,medium and high dose group.The serum fasting blood glucose(FBG),urine protein,serum creatinine(Scr) and urea nitrogen(BUN) contents of rats was detected by automatic biochemical analyzer. The serum interleukin-6(IL-6),interleukin-8(IL-8) and tumor necrosis factor-α(TNF-α) contents of rats were detected by enzyme-linked immunosorbent assay(ELISA). The kidney index of rats was measured by gravimetric method. The pathological changes of renal tissue were detected by HE staining. The expression of ANGPTL-4in renal tissue was detected by protein immunoblotting(WB). Results: The FBG,urinary protein,Scr,BUN,IL-6,IL-8,TNF-α,renal index and ANGPTL-4expression level in renal tissue of the medium and the high dose CS extract groups were significantly lower than those of the Atorvastatin group and the model group(P < 0. 05),with the increased of CS extract dose,the FBG,urine protein,Scr,BUN,IL-6,IL-8,TNF-α,renal index and ANGPTL-4expression level in renal tissue were significantly decreased(P<0. 05),in a dose-dependent manner. Conclusion: CS extract can reduce the expression level of ANGPTL-4in renal tissue and protect the kidney of DN rats,which provides a theoretical basis for the clinical treatment of DN.
引文
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[15]郑茜文.血管生成素样蛋白4在肿瘤生长与转移中的作用研究进展[J].西南军医,2014,16(2):219~222
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[19] Zhu H,Bunn HF. signal transduction:How do cells sense oxygen[J]. Science,2001,292(5516):449~451
[20] Chugh S S,Clement L C,MacéC. New Insights Into Human Minimal Change Disease:Lessons From Animal Models[J]. American Journal of Kidney Diseases the Official Journal of the National Kidney Foundation,2012,59(2):284~292
[2]方飞,夏碧珍,邹慧龙,等.糖尿病肾病血液透析患者并发症一例的药学监护[J].中国药物与临床,2015,15(10):1507~1508
[3]殷建,欧妍.阿托伐他汀对糖尿病肾病患者肾功能相关血清指标及肾脏纤维化的影响观察[J].河北医学,2015,21(1):49~52
[4]秦峰,蔡辉.青藤碱药理作用研究进展[J].现代中药研究与实践,2016,30(4):81~86
[5]方敬,陈志强,范焕芳,等.青藤碱对Ms PGN大鼠肾脏病理及TNF-a表达的影响[J].中成药,2010,32(5):854~855
[6]黄恬,蔡稀,钟玲.厄洛替尼减轻STZ诱导的糖尿病肾病模型大鼠的肾损伤[J].中国病理生理杂志,2017,33(8):1460~1466
[7]王玉,李强.细胞因子与糖尿病肾病[J].中国综合临床,2015,31(4):378~382
[8]许建梅.中药组分对糖尿病肾病大鼠肾功能保护作用的机理研究[D].北京中医药大学,2015
[9] Eboh C,Chowdhury T A. Management of diabetic renal disease[J]. Annals of Translational Medicine,2015,3(11):154~162
[10]王德伟.肾消灵汤治疗糖尿病肾病的疗效观察[J].中国中西医结合肾病杂志,2013,14(3):258~259
[11]张曼玲,张莹雯.从糖尿病肾病病机论中医药对糖尿病肾病治疗的研究进展[J].天津中医药,2017,34(9):640~644
[12]宋立群,李灼,贠捷,等.从《伤寒论》“少阴负趺阳”论治糖尿病肾病Ⅳ期[J].中国中西医结合肾病杂志,2017,18(3):189~191
[13]王博.青藤碱对小鼠肾脏缺血再灌注损伤的保护作用及机制研究[D].上海交通大学,2011
[14]龙文.青藤碱治疗糖尿病肾病对T淋巴细胞亚群的影响及临床疗效观察[D].湖北中医药大学,2016
[15]郑茜文.血管生成素样蛋白4在肿瘤生长与转移中的作用研究进展[J].西南军医,2014,16(2):219~222
[16]赵苇苇,龚伟,杨叶虹,等.血管生成素样蛋白2与炎症相关性疾病的研究进展[J].中国病理生理杂志,2012,28(11):1986~1990
[17]李文娜,崔静,于晓,等. 2型糖尿病肾病患者血清及尿液血管生成素样蛋白4的表达变化及意义[J].山东医药,2016,56(29):47~49
[18]章丽萍,杜晓刚.血管生成素样蛋白4及其在肾损伤中的研究进展[J].中华临床医师杂志:电子版,2013,7(8):3555~3557
[19] Zhu H,Bunn HF. signal transduction:How do cells sense oxygen[J]. Science,2001,292(5516):449~451
[20] Chugh S S,Clement L C,MacéC. New Insights Into Human Minimal Change Disease:Lessons From Animal Models[J]. American Journal of Kidney Diseases the Official Journal of the National Kidney Foundation,2012,59(2):284~292