精氨酸双糖苷对糖尿病肾病小鼠的治疗作用及基因转化生长因子-β1和胶原蛋白Ⅳ相关性研究  

Therapeutic Effect of Arginyl-Fructosyl-Glucose on Diabetic Nephropathy Mice and Correlation of Gene TGF-β1 and Collagen-Ⅳ

作　　者：佘欣鑫 高铭彤 刘兴龙[1] 曾露露[1] 丁传波[1] 赵婷[1] 郑毅男[1] 刘文丛[1] 徐晓华[2] SHE Xin-xin;GAO Ming-tong;LIU Xing-long;ZENG Lu-lu;DING Chuan-bo;ZHAO Ting;ZHENG Yi-nan;LIU Wen-cong;XU Xiao-hua(College of Chinese Medicinal Materials,Jilin Agricultural University,Changchun 130118,China;Department of Nephrology,China-Japan Friendship Hospital,Jilin University,Changchun 130033,China)

机构地区：[1]吉林农业大学中药材学院,长春130118 [2]吉林大学中日联谊医院肾病科,长春130033

出　　处：《中国药学杂志》2018年第19期1645-1651,共7页Chinese Pharmaceutical Journal

基　　金：长春市医药健康产业发展科技攻关项目资助(17YJ013)

摘　　要：目的探究精氨酸双糖苷(AFG)对糖尿病肾病(DN)小鼠肾脏的保护作用及转化生长因子(TGF)-β1和胶原蛋白Ⅳ基因表达相关性研究。方法随机选取12只小鼠为空白对照组,其余均用高脂饲料和链脲佐菌素(STZ)诱导DN小鼠模型,分为DN模型组、二甲双胍组、10,20,40 mg·kg-1AFG组,各组分别干预5周,每周检测小鼠血糖浓度,称量小鼠体重,5周末称量小鼠最后体重,计算肾指数,检测24 h尿蛋白总量和血清肌酐(SCr)、血尿素氮(BUN)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、过氧化氢酶(CAT)和总抗氧化能力(T-AOC); HE染色观察肾脏病理变化情况;实时荧光定量PCR(RT-PCR)检测肾脏中TGF-β1、胶原蛋白ⅣmRNA的表达情况。结果 AFG给药组的尿蛋白、TC、TG、HDLC的含量与模型组相比较有显著的下降趋势;经AFG给药组干预后的SOD、GSH、CAT、T-AOC含量与模型组相比较有明显的上升趋势,病理状况减轻; AFG各剂量组小鼠肾脏中TGF-β1和胶原蛋白Ⅳ基因表达量与模型组相比均显著降低。结论 AFG能降低小鼠24 h尿蛋白总量、减轻肾脏病理损伤、减少肾脏中TGF-β1和胶原蛋白Ⅳ基因的表达,对糖尿病引起的肾损伤有一定的保护作用。OBJECTIVE To investigate the mechanism and the protective effect of arginyi-fructosyl-glucose（AFG） on the kidney of diabetic nephropathy（DN） mice and the correlation between TGF-β1 and collagen IV. METHODS Twelve mice were randomly selected as control group; all others were induced by streptozotocin （STZ）. The mice were randomly divided into 5 groups, each of which has 12 mice, DN model group, metformin group, 10,20,40 mg ·kg^-1 AFG group; each group was treated for 5 weeks, during when mice were weighed weekly and blood glucose concentration were measured. At the end of 5 weeks, the final body weight and the renal index of the mice was calculated; 24 h urinary protein and blood biochemical indexes were recorded （TC, TG, HDL-C, SCr, BUN, SOD, GSH, CAT, T-AOC） ; the pathological changes of the kidney was observed using HE staining. The expressions of TGF- β1 and collagen IV mRNA in kidneys were detected by real-time fluorescence quantitative PCR （RT-PCR）. RESULTS The levels of urinary protein, TC, TG and HDL-C in the AFG group were significantly lower than those in the control group. The contents of SOD, GSH, CAT and T-AOC in the AFG-treatment group were significantly higher than those in the control group. Pathological condition was relieved; the mRNA expression of TGF-β1 and collagen Ⅳ in the kidneys of each dose group was significantly lower than that of the control group. CONCLUSION AFG protects the kidneys by reducing the total amount of 24 h urinary protein, decreasing renal pathological damage and decreasing the expression of TGF-β1 and collagen IV genes in kidney.

关 键 词：小鼠 精氨酸双糖苷 糖尿病肾病 转化生长因子-Β1 胶原蛋白Ⅳ 

分 类 号：R965.1[医药卫生—药理学]