糖肾平对糖尿病肾病大鼠肾脏保护作用及对足细胞标志蛋白Podocalyxin影响
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摘要
目的:探讨糖肾平对糖尿病肾病Wistar大鼠肾脏保护作用及其对足细胞标志蛋白Podocalyxin的影响。方法:将74只Wistar大鼠随机分组为:正常组10只,造模组64只。釆用空腹状态下,一次性腹腔注射STZ(45 mg/kg)进行造模;将造模成功的大鼠再按照体质量随机分为模型组、厄贝沙坦组、糖肾平小剂量组和糖肾平大剂量组。观察大鼠一般状态、体重,检测24 h尿蛋白定量。14周末,股动脉取血,检测血清中尿素氮(Blood ureanitrogen,BUN)、肌酐(Serum creatinine,Scr)含量。肾组织石蜡切片进行HE、Masson染色,观察肾组织病理变化。检测大鼠肾组织中Podocalyxin蛋白表达水平。结果:糖肾平对STZ诱导的DKD大鼠药效学影响:与模型组比较,经过糖肾平治疗后,各组大鼠体质量、皮毛光泽度、饮食、活动状态均有不同程度改善,糖肾平大、小剂量治疗组体质量均有不同程度增长(P<0.01);与模型组比较,糖肾平各组治疗后,从第2周起DKD大鼠24 h尿蛋白定量显著降低(P<0.01);与模型组比较,治疗后血BUN、Scr降低(P<0.05或P<0.01)。与模型组相比,糖肾平治疗组Podocalyxin蛋白水平明显增高(P<0.01)。结论:糖肾平可抑制DKD Wistar大鼠足细胞损伤,对其肾脏具有保护作用。
Objective:To investigate the protective effect of Tangshenping on renal function of diabetic nephropathy Wistar rats and its effect on podocyte marker protein Podocalyxin. Methods:The effect of Tangshenping on the pharmacodynamics of STZ-induced DKD rats:74 Wistar rats were randomly divided into 10 groups in normal group and 64 in model group. In the fasting state,one-time intraperitoneal injection of STZ(45 mg/kg)was used for modeling;According to body weight,rats with successful model were randomly divided into model group,irbesartan group,Tangshenping small dose group and large dose group. The general state and body weight of the rats were observed,and the 24-hour urine protein was measured. At the end of 14 weeks,blood was taken from the femoral artery to detect the content of blood urea nitrogen(BUN),serum creatinine(Scr). The paraffin sections of renal tissues were stained with HE,Mallory,PASM-HE and Masson to observe the pathological changes of renal tissues. The expression level of Podocalyxin protein in rat kidney tissue was measured. Results:The effect of Tangshenping on the pharmacodynamics of STZ-induced DKD rats:Compared with the model group,after treatment with Tangshenping,the body weight,fur gloss,diet and activity status of the rats in each group were improved to some extent. The body weight of the rats with large and small doses of Tangshenping was increased in different degrees(P<0.01);Compared with the model group,after treatment with each group of Tangshenping,from the second week onwards,the urinary protein level of DKD rats was significantly(P<0.01). Compared with the model group,the blood BUN,Scr decreased after treatment(P<0.05 or P<0.01). Compared with the model group,the level of Podocalyxin protein in the treatment group was significantly increased(P<0.01). Conclusion:Tangshenping could inhibit the podocytes injury and protect the kidneys of DKD Wistar rats.
Objective:To investigate the protective effect of Tangshenping on renal function of diabetic nephropathy Wistar rats and its effect on podocyte marker protein Podocalyxin. Methods:The effect of Tangshenping on the pharmacodynamics of STZ-induced DKD rats:74 Wistar rats were randomly divided into 10 groups in normal group and 64 in model group. In the fasting state,one-time intraperitoneal injection of STZ(45 mg/kg)was used for modeling;According to body weight,rats with successful model were randomly divided into model group,irbesartan group,Tangshenping small dose group and large dose group. The general state and body weight of the rats were observed,and the 24-hour urine protein was measured. At the end of 14 weeks,blood was taken from the femoral artery to detect the content of blood urea nitrogen(BUN),serum creatinine(Scr). The paraffin sections of renal tissues were stained with HE,Mallory,PASM-HE and Masson to observe the pathological changes of renal tissues. The expression level of Podocalyxin protein in rat kidney tissue was measured. Results:The effect of Tangshenping on the pharmacodynamics of STZ-induced DKD rats:Compared with the model group,after treatment with Tangshenping,the body weight,fur gloss,diet and activity status of the rats in each group were improved to some extent. The body weight of the rats with large and small doses of Tangshenping was increased in different degrees(P<0.01);Compared with the model group,after treatment with each group of Tangshenping,from the second week onwards,the urinary protein level of DKD rats was significantly(P<0.01). Compared with the model group,the blood BUN,Scr decreased after treatment(P<0.05 or P<0.01). Compared with the model group,the level of Podocalyxin protein in the treatment group was significantly increased(P<0.01). Conclusion:Tangshenping could inhibit the podocytes injury and protect the kidneys of DKD Wistar rats.
引文
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[3]Mathieson PW. The podocyte as a target for thraplies-new and old[J]. Nat Rev Nephrol,2011,8(1):52-56.
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[6]Ha TS,Park HY,Seong SB,et al. AngiotensinⅡinduces endoplasmic reticulum stress in podocyte,which would be further augmented by PI3-kinase inhibition[J]. Clin Hypertens,2015,21:13.
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[9]冯涛,王彩丽.氧化应激在糖尿病肾病足细胞凋亡中的作用[J].国外医药:抗生素分册,2014,35(1):6-7.
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[11]王之琳,赵宗江.赵宗江教授治疗糖尿病肾病的学术思想及临床经验撷英[J].世界科学技术-中医药现代化,2015,17(10):2162-2166.
[12]苗永辉,赵宗江,张新雪,等.糖尿病肾病“肾痿”学说的建立与阐释[J].世界科学技术-中医药现代化,2017,19(6):1031-1037.
[13]傅强,王世东,肖永华,等.吕仁和教授分期辨治糖尿病学术思想探微[J].世界中医药,2017,12(1):21-24.
[14]闫凯,温乔,谢璇,等.王暴魁“清热凉血”法治疗糖尿病肾病经验介绍[J].环球中医药,2017,10(6):612-613.
[15]谢绍锋,曹雯,胡咏新,等.芪葵颗粒对2型糖尿病肾病患者蛋白尿及炎症因子的影响[J].世界科学技术-中医药现代化,2017,19(1):149-153.
[16]宇汝翠,陆智慧,李平,等.益气养阴通络方治疗早期糖尿病肾病的临床研究[J].南京中医药大学学报,2017,33(1):101-103.
[17]赵宗江,豆小妮,张新雪.糖尿病肾病“肾痿”假说探讨[J].中医杂志,2011,52(S1):8-10.
[18]杜磊,施鹏,赵宗江,等.糖肾平含药血清对高糖+LPS刺激足细胞增殖与凋亡的影响[J].中华中医药杂志,2013,28(6):1842-1845.
[19]杜磊,赵敬,赵宗江,等.糖肾平对高糖+LPS刺激足细胞TGF-β1/Smad7信号转导通路影响的研究[J].中国中西医结合肾病杂志,2013,14(2):107-110.
[20]Gnudi L. Cellular and molecular mechanisms of diabetic glomerulopathy[J]. Nephrol Dial Transplant,2012,27(7):2642-2649.
[21]Hara M,Yamagata K,Tomino Y,et al. Urinary podocalyxin is an early marker for podocyte injury in patients with diabetes:establishment of a highly sensitive ELISA to detect urinary podocalyxin[J]. Diabetologia,2012,55(11):2913-2919.
[22]Asanuma K,Mndel P. The role of podocytes in glomerular pathobiology[J]. Clin Exp Nephrol,2003,7(4):255-259.
[23]Hara M,Yanagihara T,Kihara I,et al. Apical cell membranes are shed into urine from injured podocytes:A novel phenomenon of podocyte injury[J]. J Am Soc Nephrol,2005,16(2):408-416.
[2]邢玲玲.PI3K/AKT通路在糖尿病肾病足细胞损伤中的作用[D].石家庄:河北医科大学,2012.
[3]Mathieson PW. The podocyte as a target for thraplies-new and old[J]. Nat Rev Nephrol,2011,8(1):52-56.
[4]CAO Y,HAO Y,LI H,et al. Role of endoplasmic reticulum stress in apoptosis of differentiated mouse podocytes induced by high glucose[J].Int J Mol Med,2014,33(4),809-816.
[5]YUAN Y,XU X,ZHAO C,et al. The roles of oxidative stress,endoplasmic reticulum stress,and autophagy in aldosterone/mineralocorticoid receptor-induced podocyte injury[J]. Lab Invest,2015,95(12):1374-1386.
[6]Ha TS,Park HY,Seong SB,et al. AngiotensinⅡinduces endoplasmic reticulum stress in podocyte,which would be further augmented by PI3-kinase inhibition[J]. Clin Hypertens,2015,21:13.
[7]DONG Z,WU P,LI Y,et al. Myocardial infarction worsens glomerular injury and microalbuminuria in rats with prexisting renal impairment accompanied by the activation of ER stress and inflammation[J].Mol Biol Rep,2014,41(12):7911-7921.
[8]Madhusudhan T,WANG H,DONG W,et al. Defective podocyte insulin signalling through p85-XBP1 promotes ATF6-dependent maladaptive ER-stress response in diabetic nephropathy[J]. Nat Commun,2015,6:6496.
[9]冯涛,王彩丽.氧化应激在糖尿病肾病足细胞凋亡中的作用[J].国外医药:抗生素分册,2014,35(1):6-7.
[10]吕伟,齐栋,张燕.足细胞凋亡在糖尿病肾病发病中的作用[J].医学综述,2010,16(2):269-271.
[11]王之琳,赵宗江.赵宗江教授治疗糖尿病肾病的学术思想及临床经验撷英[J].世界科学技术-中医药现代化,2015,17(10):2162-2166.
[12]苗永辉,赵宗江,张新雪,等.糖尿病肾病“肾痿”学说的建立与阐释[J].世界科学技术-中医药现代化,2017,19(6):1031-1037.
[13]傅强,王世东,肖永华,等.吕仁和教授分期辨治糖尿病学术思想探微[J].世界中医药,2017,12(1):21-24.
[14]闫凯,温乔,谢璇,等.王暴魁“清热凉血”法治疗糖尿病肾病经验介绍[J].环球中医药,2017,10(6):612-613.
[15]谢绍锋,曹雯,胡咏新,等.芪葵颗粒对2型糖尿病肾病患者蛋白尿及炎症因子的影响[J].世界科学技术-中医药现代化,2017,19(1):149-153.
[16]宇汝翠,陆智慧,李平,等.益气养阴通络方治疗早期糖尿病肾病的临床研究[J].南京中医药大学学报,2017,33(1):101-103.
[17]赵宗江,豆小妮,张新雪.糖尿病肾病“肾痿”假说探讨[J].中医杂志,2011,52(S1):8-10.
[18]杜磊,施鹏,赵宗江,等.糖肾平含药血清对高糖+LPS刺激足细胞增殖与凋亡的影响[J].中华中医药杂志,2013,28(6):1842-1845.
[19]杜磊,赵敬,赵宗江,等.糖肾平对高糖+LPS刺激足细胞TGF-β1/Smad7信号转导通路影响的研究[J].中国中西医结合肾病杂志,2013,14(2):107-110.
[20]Gnudi L. Cellular and molecular mechanisms of diabetic glomerulopathy[J]. Nephrol Dial Transplant,2012,27(7):2642-2649.
[21]Hara M,Yamagata K,Tomino Y,et al. Urinary podocalyxin is an early marker for podocyte injury in patients with diabetes:establishment of a highly sensitive ELISA to detect urinary podocalyxin[J]. Diabetologia,2012,55(11):2913-2919.
[22]Asanuma K,Mndel P. The role of podocytes in glomerular pathobiology[J]. Clin Exp Nephrol,2003,7(4):255-259.
[23]Hara M,Yanagihara T,Kihara I,et al. Apical cell membranes are shed into urine from injured podocytes:A novel phenomenon of podocyte injury[J]. J Am Soc Nephrol,2005,16(2):408-416.
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