Ultrastructural Changes of Gastric Smooth Muscle Cells and Relationship between Expressions of Contractile Proteins and Advanced Glycation End Products in Patients with Diabetes Mellitus / 胃肠病学

ABSTRACT

Background:Myopathy due to smooth muscle cells( SMC)abnormalities is involved in the pathogenesis of diabetic gastroparesis(DGP),however,the relationship between myopathy and advanced glycation end products(AGEs)is not fully clarified. Aims:To investigate the ultrastructural changes of gastric SMC in patients with diabetes mellitus( DM)and the relationship between expressions of contractile proteins and AGEs. Methods:Full-thickness gastric specimens from 30 gastric neoplasm patients undergoing gastrectomy from July 2012 to December 2012 at the First Affiliated Hospital with Nanjing Medical University were collected. Of them 15 patients had DM( DM group)and the other 15 patients without ( control group). Ultrastructure of SMC was observed by transmission electron microscopy. Expressions of three contractile proteins[ myosin heavy chains( MHC),α-actin and calponin]and Nε-carboxymethyllysine( CML),the key component of AGEs in gastric muscular layer were determined by Western blotting,and expressions of MHC,α-actin and calponin mRNA were determined by real-time PCR. Correlations of mRNA expressions of three contractile proteins with protein expression of CML were analyzed by Pearson correlation coefficient. Results:In DM group,significant ultrastructural changes were found in gastric SMC,including disruption of gap junction,swelling of mitochondria,occurring of lipofuscin in cytoplasm,increase in cell membrane alveolae,and thickening of basal lamina. Protein and mRNA expressions of muscular MHC,α-actin and calponin were significantly lower in DM group than in control group(P all ﹤0. 01),while protein expression of CML was significantly higher in DM group(P ﹤0. 01). In gastric muscular layer of DM group, negative correlations were found between expressions of MHC,calponin mRNA and CML protein(r= -0. 59,P=0. 02;r= -0. 63,P=0. 01),but no correlation was seen between α-actin mRNA and CML protein(r= -0. 49,P=0. 06). Conclusions:Disruption of SMC ultrastructure,decrease in contractile proteins and increase in AGEs are existed in gastric muscular layer of DM patients,and there is a negative correlation between contractile proteins and AGEs. These changes may cause impaired contractility of SMC,and subsequently lead to gastric motility disorders in diabetic patients.