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自主神经重塑可能通过下调基质金属蛋白酶2,导致链脲佐菌素诱导的糖尿病大鼠主动脉夹层发生率降低。

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

作者信息

Hu Rui, Wang Zhiwei, Ren Zongli, Liu Min

机构信息

Department of Cardiovascular Surgery, Renmin Hospital of Wuhan University, No.238 Jiefang Road, Wuhan, Hubei, People's Republic of China.

Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.

出版信息

BMC Cardiovasc Disord. 2016 Oct 21;16(1):200. doi: 10.1186/s12872-016-0375-3.

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.

摘要

背景

流行病学研究报告称糖尿病患者主动脉夹层(AD)的发病率较低,但确切机制尚不清楚。我们旨在研究糖尿病(DM)对AD形成可能的保护作用,重点关注自主神经重塑。

方法

采用腹腔注射链脲佐菌素(STZ)诱导糖尿病,联合口服β-氨基丙腈(BAPN)及单侧肾动脉狭窄(URAS)诱导AD。将60只SD大鼠平均随机分为四组(正常组、DM组、URAS+BAPN口服治疗组、DM+URAS+BAPN口服治疗组)。大鼠喂养6周,记录AD发生数量,并处死剩余大鼠。采集胸主动脉,评估形态学变化。评估酪氨酸羟化酶(TH)、胆碱乙酰转移酶(ChAT)、基质金属蛋白酶2(MMP2)和基质金属蛋白酶9(MMP9)的表达。

结果

S+B组共发现7例AD,DM大鼠未发生AD。糖尿病大鼠AD发病率较低(P<0.01)。在解剖的主动脉中,胶原沉积增加而弹性纤维断裂。糖尿病大鼠的这些病理变化减轻。糖尿病大鼠ChAT表达较低(P<0.01)。URAS+BAPN治疗使正常大鼠TH表达及糖尿病大鼠ChAT表达升高(P<0.001)。URAS+BAPN处理后所有大鼠MMP2和MMP9表达均升高,但糖尿病大鼠MMP2升高幅度较小(P<0.001)。

结论

STZ诱导的糖尿病大鼠在接受URAS和BAPN治疗后AD发病率较低,这种保护作用可能归因于自主神经支配改变以及MMP2可能的相关下调。

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