磷酸鞘胺醇参与KkAy 2型糖尿病小鼠胰腺纤维化发病机制探讨

Sphingosine phosphate participates in the pathogenesis of pancreatic fibrosis in KkAy type 2 diabetic mice

目的探讨磷酸鞘胺醇(sphingosine 1-phosphate,S1P)是否参与Kk Ay 2型糖尿病小鼠胰腺纤维化的发生,这一过程是否和转化生长因子-β1(transforming growth factor-β1,TGF-β1)相关。方法应用Real-time RTPCR的方法检测Kk Ay 2型糖尿病小鼠及C57小鼠胰腺中鞘胺醇激酶1(Sph K1)的mRNA水平,并检测反映胰腺星状细胞活化的指标平滑肌肌动蛋白α(α-smooth muscle actin,α-SMA)、TGF-β1以及细胞外基质的主要成分Ⅰ型胶原[collagenα1(Ⅰ),Colα1(Ⅰ)]和Ⅲ型胶原[collagenα1(Ⅲ),Colα1(Ⅲ)]的水平。结果与对照组C57小鼠相比,Kk Ay 2型糖尿病小鼠胰腺高表达Sph K1、TGF-β1、α-SMA、Colα1(Ⅰ)及Colα1(Ⅲ),并且Sph K1与TGF-β1存在明显正相关。结论磷酸鞘胺醇可能参与了Kk Ay 2型糖尿病小鼠胰腺纤维化的发生,并且这一过程可能与TGF-β1相关。

Objective To explore whether sphingosine 1-phosphate(S1 P)is involved in pancreatic fibrosis in Kk Ay type 2 diabetic mice,and whether this process is related to transforming growth factor-β1(TGF-β1).Methods Real-time(RT)-PCR was used to detect the level of sphingosine kinase 1(Sph K1),TGF-β1 and smooth muscle actinα(α-SMA),which were measured as an index that reflects the activation of pancreatic stellate cells in the pancreas in Kk Ay type 2 diabetic mice and C57 mice.The main components of the extracellular matrix,collagenα1(Ⅰ)[Colα1(Ⅰ)]and collagenα1(Ⅲ)[Colα1(Ⅲ)],were also measured by Real-time RT-PCR.Results Sph K1,TGF-β1,α-SMA,Colα1(Ⅰ)and Colα1(Ⅲ)were overexpressed in the pancreas in Kk Ay type 2 diabetic mice.There was a significant positive correlation between Sph K1 and TGF-β1 in pancreatic tissue of Kk Ay type 2 diabetic mice.Conclusions S1 P may be involved in the development of pancreatic fibrosis in Kk Ay type 2 diabetic mice,and this process may be related to TGF-β1.