·糖尿病基础研究·　

　　【摘要】 目的 探讨白黎芦醇(Res)对高糖诱导的大鼠胸主动脉平滑肌细胞基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)表达的影响是否与PI3K/Akt信号通路有关。 方法 高糖体外培养大鼠胸主动脉平滑肌细胞，并应用Res和PI3K通路特异性抑制剂LY294002进行干预，MTT法检测细胞增殖活性，免疫组化法检测MMP-2、MMP-9表达，明胶酶谱法检测MMP-2、MMP-9活性，Western blot检测p-Akt、Akt蛋白表达。 结果 不同浓度Res(25、50、100 μmol/L)和LY294002(10、20、30 μmol/L)均可抑制高糖诱导的VSMCs增殖(P<0.05)，且均呈剂量依赖性，还可抑制高糖诱导的MMP-2、MMP-9表达和活性(P<0.05)。NC、HG、HG+LY294002(10、20、30 μmol/L)组总Akt表达无明显改变，HG+Res(25、50、100 μmol/L)组总Akt表达较HG组下降，但无剂量依赖性;而不同浓度的Res和LY294002可抑制高糖诱导的p-Akt表达(P<0.05)，且均呈剂量依赖性。 结论 (1)高糖上调VSMCs MMP-2、MMP-9表达，加重VSMCs增殖;(2)Res可能通过抑制高糖激活的PI3K/Akt信号通路，下调VSMCs MMP-2、MMP-9表达并降低其活性，减轻高糖引起的VSMCs增殖。

　　【关键词】 高糖;血管平滑肌细胞;基质金属蛋白酶;白藜芦醇;PI3K

The effects of resveratrol on high glucose-induced high expression of MMP-2 and MMP-9 in rat thoracic aorta smooth muscle cells and its signal mechanisms ZHANG Ning，WANG Mian，ZHOU Hong, et al. Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China

Corresponding author：WANG Mian，E-mail：wangmian66@sina.com

　　【Abstract】 Objective To explore whether the effects of resveratrol (Res) on MMP-2 and MMP-9 expression in rat thoracic aorta smooth muscle cells induced by high glucose were associated with PI3K/Akt signaling pathway. Methods Smooth muscle cells of primary culture from rat aorta were exposed to LY294002 and Res in different concentrations. The proliferating viability of VSMCs was observed by MTT assay. Immunohistochemistry (SABC) was used to examine the expression of MMP-2 and MMP-9. The activity of MMP-2 and MMP-9 was measured by SDS-PAGE zymography. The protein expression of p-Akt and Akt was detected by Western blot. Results Res (25, 50, 100 μmol/L) and LY294002 (10, 20, 30 μmol/L) can inhibit the proliferation of VSMCs induced by high glucose in a dose-dependent manner (P<0.05). The expression and activity of MMP-2 and MMP-9 induced by high glucose can be inhibited by Res (25, 50, 100 μmol/L) and LY294002 (10, 20, 30 μmol/L) (P<0.05). The expression of total Akt protein in NC group, HG group and HG plus LY294002 (10, 20, 30 μmol/L) group had no significant difference among these groups. However, Res (25, 50, 100 μmol/L) can inhibit the expression of total Akt protein induced by high glucose with no dose-dependence. Res (25, 50, 100 μmol/L) and LY294002 (10, 20, 30 μmol/L) down-regulated the expression of p-Akt protein induced by high glucose in a dose-dependent manner (P<0.05). Conclusion (1) High glucose up-regulates the expression of MMP-2 and MMP-9 in VSMCs and increases VSMCs proliferation. (2) Res may inhibit the high glucose-induced hing experssion of MMP-2 and MMP-9 of VSMCs activated through suppressing PI3K/Akt signaling pathway, and reduce the high glucose-induced proliferation of VSMCs.

　　【Key words】 High glucose;VSMCs;MMPs;resveratrol;PI3K