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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,噻唑蓝(MTT)法检测细胞增殖活性,免疫组织化学法检测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、100μmol/L)和LY294002(10、20、30μmol/L)均可抑制高糖诱导的血管平滑肌细胞(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、30μmol/L)组总Akt表达无明显改变,HG+Res(25、50、100μmol/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。
Objective To investigate whether resveratrol may affect the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in rat aortic smooth muscle cells induced by high glucose and PI3K / Akt Signal path related. Methods Rat thoracic aorta smooth muscle cells were cultured in vitro with high glucose. Res and PI3K pathway inhibitor LY294002 were used for intervention. Cell proliferation was measured by MTT assay. The expressions of MMP-2, MMP-9 The activity of MMP-2 and MMP-9 was detected by gelatin zymography. The protein expressions of p-Akt and Akt were detected by Western blot. Results Res (25,50,100μmol / L) and LY294002 (10,20,30μmol / L) all inhibited the proliferation of vascular smooth muscle cells (VSMCs) induced by high glucose (P <0.05) , But also inhibited the high glucose-induced MMP-2, MMP-9 expression and activity (P <0.05). The total Akt expression in NC, HG, HG + LY294002 (10, 20, 30μmol / L) group had no significant change, while the total Akt expression in HG + Res group decreased compared with HG group ; While different concentrations of Res and LY294002 could inhibit the expression of p-Akt induced by high glucose (P <0.05), both in a dose-dependent manner. (2) Res may down-regulate the expression of MMP-2 and MMP-9 in VSMCs by inhibiting the PI3K / Akt signaling pathway induced by high glucose Its activity, reduce high-glucose-induced VSMCs proliferation.