津力达颗粒改善1型糖尿病大鼠肝损伤的机制研究  

Protective mechanism of Jinlida granules against liver injury in a rat model of type 1 diabetes mellitus

作　　者：叶菲[1] 刘子毓[1] 陈海燕 陈向芳[1] 刘志民[1] 

机构地区：[1]第二军医大学长征医院内分泌科,上海200003

出　　处：《药学服务与研究》2016年第2期104-108,共5页Pharmaceutical Care and Research

摘　　要：目的:探讨津力达颗粒对1型糖尿病大鼠肝脏损伤的保护作用及可能机制。方法:SD糖尿病模型大鼠随机分为糖尿病模型组(DM)、津力达颗粒治疗组(JLD),另设正常对照组(NC),每组5只。对NC、DM和JLD组大鼠,分别灌胃给予5%羧甲基纤维素钠(CMC),5%CMC和JLD 3g/kg,每日1次,共8周。最后一次给药后24h,测定空腹血糖(BG)、糖化血红蛋白(HbA1C);放射免疫分析法测定血液透明质酸(HA)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原(PC-Ⅲ)、血清层粘连蛋白(LN)含量;酶联免疫吸附分析(ELISA)法测定血ALT、AST、碱性磷酸酶(alkaline phosphates,AKP)活性和肝组织血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)含量;免疫印迹法检测肝组织转化生长因子-β1(TGF-β1)蛋白和p-Smad2/3蛋白表达;实时定量荧光PCR技术分析肝组织AngⅡmRNA、Smad2 mRNA、Smad3 mRNA表达。结果:DM组和NC组相比,BG、HbA1C、ALT、AST、AKP、HA、LN、PC-Ⅲ、Ⅳ-C显著升高(P<0.01);肝组织中AngⅡ含量,TGF-β1蛋白和p-Smad2/3蛋白表达增高(P<0.01),肝脏Smad2mRNA、Smad3mRNA和AngⅡmRNA表达显著上调(P<0.01)。与DM组大鼠比较,JLD组大鼠的BG、HbA1C、ALT、AST、AKP、HA、LN、PC-Ⅲ、Ⅳ-C水平均显著降低(P<0.01),肝组织AngⅡ含量和p-Smad2/3蛋白表达显著降低(P<0.01),AngⅡmRNA、Smad2mRNA、Smad3mRNA表达均显著下调(P<0.01),而肝脏TGF-β1蛋白表达水平无明显降低。结论:津力达颗粒对1型糖尿病大鼠的肝损伤有保护作用,其机制可能与降低肝组织AngⅡmRNA表达和肝组织AngⅡ含量,以及降低AngⅡ非依赖于TGF-β1对p-Smad2/3的调节有关。Objective：To investigate the protective effects of Jinlida granules（JLD）on the liver injury in a rat model of type 1diabetes mellitus（DM）and the possible mechanism involved.Methods：The SD diabetes model rats were randomly divided into the diabetes model group（or DM group）and the Jinlida granule treatment group（or the JLD group）,each consisting of 5rats,and another 5rats were assigned as the normal control group（or the NC group）.For the rats in the NC,DM and JLD groups,5%carboxy methyl cellulose（CMC）,5% CMC and JLD suspensions at a dosage of 3g/kg were administered by gavage once a day for 8 weeks.The levels of fasting blood glucose（BG）and glycosylated hemoglobin（HbA1C）were detected at hour 24 following the last medication.The blood levels of hyaluronic acid（HA）,Ⅳtype collagen（Ⅳ-C）,procollagen Ⅲ（PC-Ⅲ）and laminin（LN）were analyzed by radioimmunoassay.The activities of ALT,AST,alkaline phosphates（AKP）in blood and the content of angiotensinⅡ（AngⅡ）in the liver tissue were measured by ELISA.The expression levels of transforming growth factor-β1（TGF-β1）protein and p-Smad2/3proteins in the liver tissue were detected by Western blot.And the expression levels of Ang Ⅱ mRNA,Smad2 mRNA and Smad3 mRNA in the liver tissue were detected by real time PCR.Results：When comparisons were made between the DM and NC groups,the levels of BG,HbA1 C,ALT,AST,AKP,HA,LN,PC-Ⅲ andⅣ-C were elevated significantly（P〈0.01）.AngⅡcontent in the liver tissue and the expression levels of TGF-β1,p-Smad2/3,p-Smad2 mRNA,p-Smad3 mRNA,Ang Ⅱ mRNA in the liver tissue were up-regulated significantly（P〈0.01）.As compared with those of the DM group,the levels of BG,HbA1 C,ALT,AST,AKP,HA,LN,PC-Ⅲ,andⅣ-C were significantly decreased（P〈0.01）,and the content of AngⅡ and expression levels of p-Smad2/3were significantly decreased（P〈0.01）in the JLD group.The expression levels of Ang Ⅱ mRNA,Smad2 mRNA and Smad3 mRNA were all down-regulated（P〈0.01�

关 键 词：津力达颗粒 糖尿病 血管紧张素Ⅱ SMAD2/3 大鼠 

分 类 号：R285.5[医药卫生—中药学]