左归丸对妊娠糖尿病大鼠血清相关指标及胰腺PDX-1表达的影响

Effect of Zuoguiwan on Serum Related Indexes and Pancreatic PDX-1 Expression in GDM Rats

目的:研究左归丸母代干预对妊娠糖尿病(GDM)模型大鼠血清及以胰腺指标改善作用的影响。方法:通过雌雄同笼及腹腔注射链脲佐菌素(STZ)的方法复制GDM孕鼠模型,采用随机数字表法将孕鼠分为正常组,模型组,门冬胰岛素组(20 U·kg^-1),左归丸低、中、高剂量组(2.5,5.0,10.0 g·kg^-1)。各组分别灌服相应药物2周,正常组和模型组予以等体积生理盐水,采用酶联免疫吸附测定(ELISA)检测大鼠血清胰岛素,空腹血糖(FBG),及炎性因子肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6),白细胞介素-8(IL-8)的水平;蛋白免疫印迹法(Western blot),实时荧光定量聚合酶链式反应(Real-time PCR)检测大鼠胰腺十二指肠同源盒因子-1(PDX-1)蛋白及mRNA的表达水平。结果:与正常组比较,模型组大鼠空腹血糖及炎性因子TNF-α,IL-6均显著升高(P<0.01),IL-8水平明显升高(P<0.05),大鼠血清胰岛素水平、胰腺PDX-1蛋白及mRNA表达均显著降低(P<0.01);与模型组比较,门冬胰岛素组血糖及血清炎性因子IL-8水平显著降低(P<0.01),血清胰岛素水平、胰腺PDX-1蛋白及mRNA表达均显著升高(P<0.01),左归丸中剂量组血糖及炎性因子TNF-α,IL-6,IL-8显著降低(P<0.01),血清胰岛素水平、胰腺PDX-1蛋白及mRNA表达均显著升高(P<0.01)。结论:左归丸可能通过降低GDM大鼠血清炎性因子水平,减少炎症反应及氧化应激反应的发生,以提升胰岛素的分泌,同时上调PDX-1蛋白和mRNA的表达,改善胰岛素抵抗,减少胰岛β细胞的损伤,降低大鼠血糖。

Objective:To investigate the effect of maternal intervention of Zuoguiwan on the improvement of serum and pancreatic index in rats of gestational diabetes mellitus(GDM).Method:The GDM pregnant rats were replicated by monogamous cage and introneal injection of streptozotocin(STZ).The pregnant rats were randomly divided into normal group,model group,insulin group(20 U·kg^-1),and low,medium and high-dose Zuoguiwan groups(2.5,5.0,10.0 g·kg^-1).The insulin group was given hypodermic injection of portal winter insulin,all drug groups were respectively administrated with corrsponding drugs for 2 weeks,once a day.Meanwhile,control group and model group were given physiological saline by gavage.After that,the levels of serum insulin,fasting plasma glucose(FBG),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-8 were measured by enzyme-linked immunosorbent assay(ELISA),protein and gene expression levels of Pancreas-duodenal homologous box factor-1(PDX-1)were respectively detected by Western blot and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).Result:Compared with normal group,FBG,TNF-αand IL-6 levels of pregnant rats in model group increased significantly(P<0.01),the level of IL-8 increased uniformly(P<0.05),and serum insulin level,protein and gene expression levels of PDX-1 decreased significantly(P<0.01).Compared with model group,FBG and serum IL-8 levels of pregnant rats in insulin group were significantly lower(P<0.01),while serum insulin level,protein and gene expression levels of PDX-1 increased significantly(P<0.01).FBG,IL-8,IL-6 and TNF-αlevels in serum of pregnant rats in medium-dose Zuoguiwan group decreased obviously,meanwhile serum insulin level,protein and gene expression levels of PDX-1 increased significantly(P<0.01).Conclusion:Zuoguiwan may promote the secretion of insulin by reducing the serum inflammatory factors in GDM rats,and at the same time up-regulate the expression of PDX-1 protein and gene,so as to restrain insulin resistance,reduce the damage of pancreatic cells and improve the blood glucose of rats.