糖通饮通过抑制TGF-β1/Smad信号通路保护早期糖尿病肾病大鼠肾组织
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摘要
目的:通过观察糖通饮对早期糖尿病肾病大鼠肾组织TGF-β1/Smad信号通路的影响,探讨其保护早期糖尿病肾病的机制。方法:雄性SD大鼠55只,随机分为正常组(N组) 10只,剩余45只采用高脂高糖饲料联合链脲佐菌素小剂量多次腹腔注射造模,将造模成功的40只均分为模型组(M组)、糖通饮组(T组)、厄贝沙坦组(Ⅰ组)及糖通饮联合厄贝沙坦组(T+Ⅰ组),T组、Ⅰ组、T+Ⅰ组均给予对应的药物灌胃治疗,N、M组均给予同等量生理盐水灌胃;于8周末处死大鼠取肾皮质检测Western blot和实时荧光定量PCR法TGF-β1、Smad2及Smad3蛋白和mRNA表达水平。结果:Western blot检测显示,与N组比较,M组大鼠肾组织TGF-β1、Smad2及Smad3蛋白表达增加(P<0.05);与M组比较,T组、Ⅰ组、T+Ⅰ组大鼠肾组织TGF-β1、Smad2及Smad3蛋白表达降低(P<0.05);实时荧光定量PCR结果显示,与N组比较,M组大鼠肾组织TGF-β1、Smad2及Smad3 mRNA表达明显增加(P<0.05);与M组比较,T组、Ⅰ组和T+Ⅰ组大鼠肾组织TGF-β1、Smad2及Smad3 mRNA表达降低(P<0.05); T组、T+Ⅰ组与Ⅰ组比较,大鼠肾组织TGF-β1、Smad2、Smad3蛋白及mRNA表达比较差异无统计学意义(P>0.05)。结论:糖通饮能够抑制早期糖尿病肾病大鼠的TGF-β1表达,下调Smad2、Smad3,有效的保护肾脏,其作用机制与抑制TGF-β1/Smads信号通路的激活有关。
Objective:To explore the mechanism of the protective effect on early diabetic nephropathy by observing the effect of Tangtong Drink on TGF-β1/Smad signaling pathway in renal tissue of rats with early diabetic nephropathy.Methods:A total of 55 male Sprague-Dawley rats were randomly divided into normal group(N Group).The remaining 45 were injected intraperitoneally with high fat and high sugar diet combined with streptozotocin for several times.The 40 SD rats that were successfully modeled were divided into model group(M Group),TangTong Drink group(T Group),irbesartan group(Ⅰ Group),and TangTong Drink + irbesartan group(T + Ⅰ Group).The T Group,ⅠGroup,and T + Ⅰ Group were given the corresponding drugs by intragastric administration,and N Group and M Group were given the same amount of normal saline.At the end of 8 weeks,the renal cortex was taken from the rats to detect the expression of TGF-β1,Smad2,Smad3 protein and mRNA.Results:The Western blot analysis showed that compared with N Group,the expression of TGF-β1,Smad2 and Smad3 protein in renal tissue of M Group increased,and the difference was statistically significant(P<0.05).Compared with M Group,the expression of TGF-β1,Smad2 and Smad3 protein in renal tissue of T Group,Ⅰ Group,and T + Ⅰ Group decreased,and the difference was statistically significant(P<0.05).The results of real-time fluorescence quantitative PCR showed that compared with N Group,the expression of TGF-β1,Smad2 and Smad3 mRNA in renal tissue of M Group increased significantly,and the difference was statistically significant(P<0.05).Compared with M Group,the expression of TGF-β1,Smad2 and Smad3 mRNA in renal tissue of T Group,I Group and T + Ⅰ Group reduced,and the difference was statistically significant(P<0.05).There was no significant difference in the expression of TGF-β1,Smad2 and Smad3 protein and mRNA among T Group,T + Ⅰ Group and Ⅰ Group Ⅰ(P>0.05).Conclusion:The famous traditional Chinese medicine Tangtong Drink can inhibit the production of TGF-β1 in rats with early diabetic nephropathy,down-regulate the expression of Smad2 and Smad3,and effectively protect the kidney.Its mechanism is related to the inhibition of the activation of the TGF-β1/Smads signaling pathway.
Objective:To explore the mechanism of the protective effect on early diabetic nephropathy by observing the effect of Tangtong Drink on TGF-β1/Smad signaling pathway in renal tissue of rats with early diabetic nephropathy.Methods:A total of 55 male Sprague-Dawley rats were randomly divided into normal group(N Group).The remaining 45 were injected intraperitoneally with high fat and high sugar diet combined with streptozotocin for several times.The 40 SD rats that were successfully modeled were divided into model group(M Group),TangTong Drink group(T Group),irbesartan group(Ⅰ Group),and TangTong Drink + irbesartan group(T + Ⅰ Group).The T Group,ⅠGroup,and T + Ⅰ Group were given the corresponding drugs by intragastric administration,and N Group and M Group were given the same amount of normal saline.At the end of 8 weeks,the renal cortex was taken from the rats to detect the expression of TGF-β1,Smad2,Smad3 protein and mRNA.Results:The Western blot analysis showed that compared with N Group,the expression of TGF-β1,Smad2 and Smad3 protein in renal tissue of M Group increased,and the difference was statistically significant(P<0.05).Compared with M Group,the expression of TGF-β1,Smad2 and Smad3 protein in renal tissue of T Group,Ⅰ Group,and T + Ⅰ Group decreased,and the difference was statistically significant(P<0.05).The results of real-time fluorescence quantitative PCR showed that compared with N Group,the expression of TGF-β1,Smad2 and Smad3 mRNA in renal tissue of M Group increased significantly,and the difference was statistically significant(P<0.05).Compared with M Group,the expression of TGF-β1,Smad2 and Smad3 mRNA in renal tissue of T Group,I Group and T + Ⅰ Group reduced,and the difference was statistically significant(P<0.05).There was no significant difference in the expression of TGF-β1,Smad2 and Smad3 protein and mRNA among T Group,T + Ⅰ Group and Ⅰ Group Ⅰ(P>0.05).Conclusion:The famous traditional Chinese medicine Tangtong Drink can inhibit the production of TGF-β1 in rats with early diabetic nephropathy,down-regulate the expression of Smad2 and Smad3,and effectively protect the kidney.Its mechanism is related to the inhibition of the activation of the TGF-β1/Smads signaling pathway.
引文
[1]ZHANG J G.Molecular mechanisms for Haikunshenxi capsule combined with conventional western medicine to improve renal function in patients with diabetic nephropathy[J].海南医科大学学报(英文版),2017,23(6):684-687.
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[4]管志敏,柏晓辉,屈璐,等.穴位埋线与糖通饮对早期糖尿病肾病大鼠血清TGF-β1和IGF-1的影响[J].贵阳医学院学报,2015,40(12):1352-1355.
[5]孙翠英,王洁,张承承,等.糖肾清1号对糖尿病肾病模型大鼠肾组织MCP-1,RANTES表达的影响[J].中国实验方剂学杂志,2018,(1):102-108.
[6]ZHOU S X,HUO D M,HE X Y,et al.High glucose/lysophosphatidylcholine levels stimulate extracellular matrix deposition in diabetic nephropathy via platelet-activating factor receptor[J].Molecular Medicine Reports,2018,17(2):2366-2372.
[7]HUI YAO LAN.Diverse Roles of TGF-β/Smads in Renal Fibrosis and Inflammation[J].International Journal of Biological Sciences,2011,7(7):1056-1067.
[8]李志杰,张悦,陆海英,等.六味地黄丸对糖尿病肾病大鼠肾组织TGF-β1-Smad通路的影响[J].时珍国医国药,2017,(8):1811-1814.
[9]LI Y,LI L,ZENG O,et al.H2S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF-β1 expression[J].Renal Failure,2016,39(1):1.
[10]王自润,张慧宇,郭敏芳,等.糖克煎剂对糖尿病大鼠肾保护作用及TGF-β1/Smad4表达的影响[J].中国中西医结合杂志,2014,34(7):826-832.
[11]刘镕,赵琴平,董惠芬,等.TGF-β信号传导通路及其生物学功能[J].中国病原生物学杂志,2014,(1):77-83.
[12]XIE S,LU K,ZHANG Y,et al.Effects of Jiangya Xiaoke prescription on TGF-β1 in diabetic nephropathy rats with hypertension and its mechanisms.[J].Int J Clin Exp Med,2015,8(4):5129-5136.
[13]黄平,陈丹,华健,等.山茱萸颗粒对糖尿病肾病大鼠TGF-β1/Smad7通路的影响[J].中国中西医结合肾病杂志,2012,13(9):762-764.
[14]贾会玉,李中南,陈光亮.糖尿病肾病中转化生长因子β1/Sma和Mad相关蛋白信号通路的作用及其相关药物研究进展[J].中国药理学与毒理学杂志,2016,30(3):266-271.
[15]丁英钧,梁文杰,庞金奎,等.肾消通络方对糖尿病肾病大鼠肾脏TGF-β1/Smad信号传导通路的影响豢[J].中国中医基础医学杂志,2015,(9):1099-1101.
[16]潘艳伶,凌湘力.糖通饮治疗早期糖尿病肾病30例[J].河南中医,2015,35(5):1068-1070.
[17]潘艳伶,凌湘力.糖通饮对早期糖尿病肾病患者尿微量白蛋白排泄率、糖脂代谢的影响[J].北方药学,2015,16(2):112-113.
[18]PERRY B,ZHANG J,SALEH T,et al.Liuwei Dihuang,a traditional Chinese herbal formula,suppresses chronic inflammation and oxidative stress in obese rats[J].Journal of Integrative Medicine,2014,12(5):447-454.
[19]ZHOU X,SUN X,GONG X,et al.Astragaloside IVfrom Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-кBin vivo and in vitro[J].International Immunopharmacology,2017,42(1):18-24.
[20]蔡琳,彭鹏,郭甜.丹参药理作用及临床研究进展[J].山东化工,2016,45(17):51-52.
[2]Al-ONAZI A S,Al-RASHEED N M,ATTIA H A,et al.Ruboxistaurin attenuates diabetic nephropathy via modulation of TGF-β1/Smad and GRAP pathways[J].Journal of Pharmacy&Pharmacology,2016,68(2):219-232.
[3]ZHAO H L,SUI Y,QIAO C F,et al.Sustained antidiabetic effects of a berberine-containing chinese herbal medicine through regulation of hepatic gene expression[J].Diabetes,2012,61(4):933-943.
[4]管志敏,柏晓辉,屈璐,等.穴位埋线与糖通饮对早期糖尿病肾病大鼠血清TGF-β1和IGF-1的影响[J].贵阳医学院学报,2015,40(12):1352-1355.
[5]孙翠英,王洁,张承承,等.糖肾清1号对糖尿病肾病模型大鼠肾组织MCP-1,RANTES表达的影响[J].中国实验方剂学杂志,2018,(1):102-108.
[6]ZHOU S X,HUO D M,HE X Y,et al.High glucose/lysophosphatidylcholine levels stimulate extracellular matrix deposition in diabetic nephropathy via platelet-activating factor receptor[J].Molecular Medicine Reports,2018,17(2):2366-2372.
[7]HUI YAO LAN.Diverse Roles of TGF-β/Smads in Renal Fibrosis and Inflammation[J].International Journal of Biological Sciences,2011,7(7):1056-1067.
[8]李志杰,张悦,陆海英,等.六味地黄丸对糖尿病肾病大鼠肾组织TGF-β1-Smad通路的影响[J].时珍国医国药,2017,(8):1811-1814.
[9]LI Y,LI L,ZENG O,et al.H2S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF-β1 expression[J].Renal Failure,2016,39(1):1.
[10]王自润,张慧宇,郭敏芳,等.糖克煎剂对糖尿病大鼠肾保护作用及TGF-β1/Smad4表达的影响[J].中国中西医结合杂志,2014,34(7):826-832.
[11]刘镕,赵琴平,董惠芬,等.TGF-β信号传导通路及其生物学功能[J].中国病原生物学杂志,2014,(1):77-83.
[12]XIE S,LU K,ZHANG Y,et al.Effects of Jiangya Xiaoke prescription on TGF-β1 in diabetic nephropathy rats with hypertension and its mechanisms.[J].Int J Clin Exp Med,2015,8(4):5129-5136.
[13]黄平,陈丹,华健,等.山茱萸颗粒对糖尿病肾病大鼠TGF-β1/Smad7通路的影响[J].中国中西医结合肾病杂志,2012,13(9):762-764.
[14]贾会玉,李中南,陈光亮.糖尿病肾病中转化生长因子β1/Sma和Mad相关蛋白信号通路的作用及其相关药物研究进展[J].中国药理学与毒理学杂志,2016,30(3):266-271.
[15]丁英钧,梁文杰,庞金奎,等.肾消通络方对糖尿病肾病大鼠肾脏TGF-β1/Smad信号传导通路的影响豢[J].中国中医基础医学杂志,2015,(9):1099-1101.
[16]潘艳伶,凌湘力.糖通饮治疗早期糖尿病肾病30例[J].河南中医,2015,35(5):1068-1070.
[17]潘艳伶,凌湘力.糖通饮对早期糖尿病肾病患者尿微量白蛋白排泄率、糖脂代谢的影响[J].北方药学,2015,16(2):112-113.
[18]PERRY B,ZHANG J,SALEH T,et al.Liuwei Dihuang,a traditional Chinese herbal formula,suppresses chronic inflammation and oxidative stress in obese rats[J].Journal of Integrative Medicine,2014,12(5):447-454.
[19]ZHOU X,SUN X,GONG X,et al.Astragaloside IVfrom Astragalus membranaceus ameliorates renal interstitial fibrosis by inhibiting inflammation via TLR4/NF-кBin vivo and in vitro[J].International Immunopharmacology,2017,42(1):18-24.
[20]蔡琳,彭鹏,郭甜.丹参药理作用及临床研究进展[J].山东化工,2016,45(17):51-52.
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