Autonomic remodeling may be responsible for decreased incidence of aortic dissection in STZ-induced diabetic rats via down-regulation of matrix metalloprotease 2

自主神经重塑可能通过下调基质金属蛋白酶2来降低链脲佐菌素(STZ)诱导的糖尿病大鼠主动脉夹层的发生率。

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Abstract

BACKGROUND: Epidemiological studies reported that diabetic patients had a lower incidence of aortic dissection (AD), but the definite mechanism is unknown. We aim to investigate the possible protective effect of diabetes mellitus (DM) on AD formation with an emphasis on autonomic remodeling. METHODS: Streptozotocin (STZ) intraperitoneal injection was applied to induce diabetes, unilateral renal artery stenosis (URAS) together with β-amino propionitrile (BAPN) oral treatment was used to induce AD. Sixty SD rats were equally and randomly divided into four groups (normal group, DM group, URAS + BAPN oral treatment group, DM + URAS + BAPN oral treatment group). Rats were fed for 6 weeks, the number of AD was recorded and remained rats were sacrificed. Thoracic aorta were harvested, morphological changes were assessed. Expression of tyrosine hydroxylase (TH), choline acetylase (ChAT), matrix metalloprotease 2 (MMP2) and matrix metalloprotease 9 (MMP9) were evaluated. RESULTS: A total of 7 AD was noted in S + B group, DM rats did not develop AD. Diabetic rats had a lower incidence of AD (P < 0.01). In dissected aorta, collagen deposition increased while elastic fiber became fragmented. These pathological changes diminished in diabetic rats. Diabetic rats had a lower expression of ChAT (P < 0.01). URAS + BAPN treatment elevated expression of TH in normal rat and ChAT in diabetic rats (P < 0.001). Expression of MMP2 and MMP9 elevated in all the rats after URAS + BAPN, but the elevation range of MMP2 in diabetic rats was smaller (P < 0.001). CONCLUSIONS: STZ-induced diabetic rats have a lower incidence of AD after URAS and BAPN treatment, this protective effect could be possibly attributed to autonomic innervation modification and possible related down-regulation of MMP2.

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