title: Protective effects of pioglitazone against immunoglobulin deposition on heart of streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have immunomodulatory and anti-inflammatory effects. The study investigated the autoimmune injuries of diabetic cardiomyopathy (DCM) and tested the hypothesis that PPAR-γ agonists suppress disordered immune responses in diabetic heart, thereby preventing evolution of DCM.
  
  
  METHODS
  STZ-induced diabetic rats were assigned to five groups: DM group, given no treatment; INS group, given insulin (4 U kg(-1) d(-1)); PIL group, given low dose pioglitazone (4 mg kg(-1) d(-1)); PIL/INS group, given both low dose pioglitazone and insulin; PIH group, given high dose pioglitazone (20 mg kg(-1) d(-1)). Normal rats (CON group) were also monitored as control. The pathologic abnormalities of hearts were observed. The immunoglobulin deposition was examined by immunohistochemistry and immunofluorescence.
  
  
  RESULTS
  At 16 weeks, interstitial fibrosis was shown in diabetic heart which was accompanied by plenty of inflammatory cells infiltrated. Pioglitazone therapy could ameliorate the cardiac injuries. Shown by immunohistochemistry, the difference of integrated optical density (IOD) of immunoglobulin deposition among each group had statistic significance. No obvious immunoglobulins were deposited in the intercellular substance of heart in CON group (IgA 290.8 ± 88.1, IgG 960.4 ± 316.0 and IgM 341.3 ± 67.9). But the deposition of immunoglobulins increased significantly in DM group (IgA 7,047.5 ± 1,328.3, P < 0.05; IgG 28,945.9 ± 5,160.7, P < 0.05 and IgM 8,580.8 ± 1,336.8, P < 0.05). Administration of pioglitazone greatly reduced the increased deposition in a dose-dependent fashion. Moreover, the statistical significance was the same with immunofluorescence analysis as with immunohistochemical examination.
  
  
  CONCLUSIONS
  The data suggest that disordered immune responses play an important role in the pathogenesis of DCM. Pioglitazone showed protective effects by inhibiting the immunoglobulin deposition on diabetic myocardium.
authors.affiliation: Department of Endocrinology, General Hospital of Tianjin Medical University, Tianjin, 300052, China.
authors.forename: M
authors.initials: M
authors.lastname: Yuan
authors.forename: M
authors.initials: M
authors.lastname: Qiu
authors.forename: J
authors.initials: J
authors.lastname: Cui
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000276:immunology* / Q000517:prevention & control*; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007136:Immunoglobulins / Q000032:analysis*; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D045162:Thiazolidinediones; D000077205:Pioglitazone