葛根芩连汤对自发肥胖型2型糖尿病ZDF大鼠FFA及NF-κB/IRS2通路的影响

Effects of Gegen Qinlian Decoction on FFA and NF-κB/IRS2 Pathway in Type 2 Diabetes Mellitus Rats with Spontaneous Obesity

目的:观察葛根芩连汤(Gegen Qinlian Decoction,GQD)对自发肥胖型2型糖尿病(T2DM)ZDF大鼠血清中游离脂肪酸(FFA)、胰腺组织中核因子(NF)-κB、胰岛素受体底物2(IRS2)的影响。方法:8只雄性ZDF(fa/+)大鼠设为正常对照组,成模的雄性ZDF(fa/fa)大鼠24只随机分为模型组、二甲双胍组和葛根芩连汤组。二甲双胍组、葛根芩连汤组分别予二甲双胍0.3 g·kg-1·d-1、葛根芩连汤13.8 g·kg-1·d-1,正常对照组和模型组给予同体积的0.9%Na Cl溶液灌胃,均连续灌胃8周。每2周测大鼠体质量、空腹血糖(fasting blood-glucose,FBG);给药8周后取材,全自动生化法检测FFA,酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测大鼠空腹胰岛素(fasting insulin,FINS)含量,计算胰岛素抵抗指数(insulin resistance index,IRI)、胰岛素敏感指数(insulin sensitivity index,ISI),免疫印迹(Western blot,WB)法检测NF-κB、IRS2的表达。结果:与正常对照组比较,模型组大鼠体质量、FBG、FFA、FINS、IRI均显著升高,ISI明显降低(P<0.01);胰腺组织中NF-κB蛋白相对表达量升高,IRS2的蛋白相对表达量下降(P<0.05,P<0.01)。与模型组比较,葛根芩连汤组大鼠体质量、FBG、FFA、FINS、IRI均明显降低,ISI明显升高(P<0.05,P<0.01);胰腺组织中NF-κB蛋白相对表达量明显降低,IRS2蛋白相对表达量明显升高(P<0.01)。结论:葛根芩连汤可有效改善胰岛素抵抗、提高组织对胰岛素的敏感性,其作用机制可能与相关低度炎症反应中的细胞因子有关。

Objective： To observe the effects of Gegen Qinlian Deeoetion（GQD）on the free fatty acids （FFA） in serum and nuclear faetor-κB （NF-κB） and insulin receptor substrate 2 （IRS2） in pancreatic tissue of Zucker diabetes fatty（ZDF） rats which as model of type 2 diabetes mellitus （T2DM）with spontaneous obesity. Methods： Eight male ZDF （fa/＋ ）rats were taken as the normal control group,and twenty four male ZDF （fa/fa）model rats were randomly divided into the model group, mefformin group and GQD group. The mefformin group was treated with mefformin at daily dose of 0.3 g/kg, the GQD group was treated with Gegen Qinlian Decoction at daily dose of 13.8 g/kg,and the normal control group and model group were treated with 0.9% NaCl solution at equivalent volume by intragastrie administration ,with a course of continuous 8 weeks. The body weight and fasting blood glucose （FBG） were measured every two weeks. After administration for 8 weeks, the samples were oolleeted. The serum level of FFA was detected by automatic biochemical analyzer, the serum level of fasting insulin （FINS） was detected by enzyme linked immunosorbent assay （ELISA）. The insulin resistance index （IRI）and insulin sensitivity index（ISI） were calculated. The expressions of NF-κB and IRS2 were detected by Western blot. Results： Compared with the normal control group, the body weight, the levels of FBG, FFA, FINS and the IRI were significantly increased and the ISI was obviously decreased in the model group （ P 〈 0. 01 ）, and the relative expression of NF-κB protein in the pancreatic tissue was increased and the relative expression of IRS2 protein was deereasod （ P 〈 0.05,P 〈 0.01 ）. Compared with the model group, the body weight, the levels of FBG, FFA, FINS and the IRI were all obviously decreased and the IS/ was obviously increased in the GQD greup（P 〈0.05 ,P 〈 0.01 ）, and the relative expression of NF-κB protein in the pancreatic tissue was obviously decreased and the relative expression of IRS2 protein was obviously increased（P 〈 0.01 ）. Conclusion： Gegen Qinlian Decoction can effectively improve the insulin resistance and enhance the tissue sensitivity. Its mechanism may be related to the eytokines in low-grade inflammatory response.