[The Role of DNA Double-strain Damage Repairing Mechanisms in Diabetic Atheroscolersis].

Objectives: To identify the role of DNA double-strain damage repairing pathway in the development of diabetics atherosclerosis.

Methods: Wistar male rats were randomly divided into three groups: control group (group A), balloon injury group (group B) and diabetes + balloon injury group (group C). Streptozotocin (STZ) was injected into rat abdomen to induce diabetes. After stabilizing high glucose, rats in group B and group C were both under aortic balloon injury technique and fed high lipid forage post-operatively. Glucose levels and weight were observed weekly. Segments of aortoa of three groups were taken at 2, 4, 6 and 8 weeks, staining of senescent β-galactosidase (SA-β-gal) staining, HE and changes of aorta under light microscope were observed. The area of tunica intima (I) and tunica media (M) in aorta was measured, and their ratio (I/M) were analyzed. Expressions of gamma-histong family 2A variant (γ-H2AX), phosphorylated ataxia telangiectasia mutated (ATM), phosphorylated checkpoint kinasen 2 (CHK2) and phosphorylated P53 were detected by immunohistochemical staining.

Results: SA-β-gal staining positive areas were dotted around in group B and group C [CM(155.3mm]but not in group A at two At the same a slight hyperlasia of aortic neointima was observed in HE staining of group B and group C. SA-β-gal staining was positive scattered within the tunica intima of aorta of group B and group C at four weeks, and HE staining promted a significantly greater of aortic neointima in the group C than that in the other two group (<0.05). Positive regions of SA-β-gal staining were more in group C than group B at six weeks. Typical atherosclerotic plaques were formed, vascular smooth muscle cells were disordered arranged and foam cells were aggregated in the plaques of group C at six weeks post-operatively, and intimal membrane areas increased than group A and group B ( <0.05). At 8 weeks, SA-β-gal positive areas in group C were greater than in group B. The arteriolar wall was markedly thickened and the lumen was narrowed. The area of intimal membrane and the I/M radio were significantly greater in group C than those in group A and group B ( <0.05). Positive expressed of γ-H2AX, phosphorylated ATM, phosphorylated CHK2 and phosphorylated P53 were observed in typical atherosclerotic foci of group C, and weaker expressed in group B.

Conclusion: Cellular senescence of vascular edothelium is triggered and DNA double-strain damage is increased in diabetes. The DNA double-strain damage repairing machines may participate in the development of diabetic atherosclerosis.