| The study was designed to investigate CT-1mRNA and CTGF expression in the cardiomyopathy of diabetic rats and the intervention of Irbesartan, to probe the role of CT-1 and CTGF in the DMCM of rats potential mechanism and to provide a new prevention and cure method.Methods78 male SD rats weighting 196±10g were randomized into 2 groups: control group (n=36) and diabetic group (n=42). Diabetes was induced by STZ 60 mg.kg-1 intraperitoneal injection and the SD rats of diabetics group were randomized into 2 groups: Irbesartan group (n=6) and untreated group (n=36), the later was subdivided into 6 groups (6 rats in each group) according to different time at 2w, 4w, 6w, 8w, 10w, 12w. Irbesartan groupwas treated with Irbesartan 50 mg·kg-1·d-1, 12w later compared with diabetic group of 12w. Blood glucose and weight of all rats were accessed once a week. Rats were killed at 2w, 4w, 6w, 8w, 10w, 12w respectively. 6 rats were selected and killed at random from the control group. Rats of Irbesartan group were killed at 12w. All killed rats should be measured BW, HW, LHW, HW/BW and LVMI. The myocardial ultrastructure of the three groups (Diabetic group, Irbesartan group, control group) were observed by electron microscope, the pathological change were observed by light microscope. ISH, IH were used to measured CT-lmRNA, CTGF respectively. Myocardial AngⅡand collagen contents were measured by radioimmunoassay and chloramines T method.Results(1) LVWI, HW/BW of diabetic group was significantly higher compared with normal group (p＜0.01). HW/BW, LVWI of Irbesartan group was lower than diabetic group (p＜0.01) and higher than normal group (p＜0.01).(2) Myocardial ultrastructure changes of the 12w diabetic rats induced by STZ: malalignment, fiber break, mitochondria apomorphosis, larger cell spaces, focal dissolve of endochylema, collagen fibers of interstitium accumulation. Diabetic cardiomyopathy has been formed. You can find that cardiocyte to line up in order, no cardiocyte augmentation, normal cell spaces in the normal group, the extent of cardiocyte degeneration and cellular necrosis was lessen in Irbesartan group.(3) The CT-lmRNA and CTGF protein express of diabetic group were improved significantly and advanced rectilinearity with the development of diabetes (p＜0.01). Col and AngⅡwere higher than normal group (p＜0.01).(4) The CT-lmRNA, CTGF protein express of Irbesartan group was lower than diabetic group (p＜0.01). Col, AngII of cardiomyopathy was lower than diabetic group (p＜0.05). Myocardial ultrastructure pathyologycal changes were improved.(5) Cardiac ventricle CT-1mRNA, CTGF and Col, AngⅡof cardiac ventricle region had correlation according to correlation analysis.Conclus ions(1) In STZ-induced diabetic SD rats, diabetic cardiomyopathy presents at 12weeks of diabetic duration.(2) Upregulation of CTGF and CT-1mRNA is strongly correlated with the concomitant accumulation of extracelluar matrix component, and is involved in the onset and progression of diabetic cardiomyopathy. There was sure relationship between the two indexes, but the pathogenesis we need further discussion.(3) Down-regulating the over expression of CT-lmRNA and CTGF in diabetic is an underlying mechanism of Irbesartan in the prevention of myocardial fibrosis and cardiac protection. AngⅡmay has relationship with this course but is not sure. |
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