Role of Cilostazol in Rats with Diabetic Lower Limb Ischemia and Its Influences on Changes in Matrix Metallopeptidase-9 and Matrix Metalloproteinase-8

Abstract

Objective: To assess cilostazol’s effect on rats with diabetic lower limb ischemia. Methods: 36 Sprague-Dawley rats were randomly separated into normal group (n = 12), model group (n = 12) and cilostazol group (n = 12). The model of diabetic lower limb ischemia was prepared and normal saline was intraperitoneally injected postoperatively into model group. Besides, cilostazol was administrated through intraperitoneal injection after establishment of model in cilostazol group. After intervention for 6 weeks, doppler blood flow imager was employed to detect blood flow, and the expressions of MMP-8 and MMP-9 were assessed via immunohistochemistry, western blotting or quantitative polymerase chain reaction (qPCR). TUNEL assay was performed to evaluate cell apop-tosis. Results: Doppler blood flow imager showed that compared with normal group, perfusion unit (PU) index was significantly reduced in the other two groups (P < 0.05) with higher value in cilosta-zol group (P < 0.05). The immunohistochemistry results revealed that in comparison with those in normal group, MMP-8 and MMP-9 positive staining was significantly elevated in the other two groups (P < 0.05) with higher level in cilostazol group than model group. In addition, MMP-8 and MMP-9 expressions were significantly elevated in other two groups (P < 0.05), with higher level in cilostazol group (P < 0.05). Moreover, the vascular wall smooth muscle cells in the other two groups had a significantly elevated apoptosis rate (P < 0.05) with higher apoptosis in cilostazol group (P < 0.05). Conclusion: Cilostazol up-regulates MMP-8 and MMP-9 to increase the apoptosis of vascular wall smooth muscle cells, thereby improving the blood flow in rats with diabetic lower limb ischemia.