The Mechanism of Cathepsins S Inhibitor Affected Ischemia-induced Neovascularization in Experimental Mice / 中国循环杂志

ABSTRACT

Objectives: To investigate the potential mechanism of cathepsins S inhibitor (CatS-I) affected ischemia-induced neovascularization in experimental mice. Methods: 8 week-old wild type (C57/BL6) mice were randomly divided into 2 groups Control group, the mice received basic diet with intraperitoneal injection of 5% carboxymethylcellulose sodium and CatS-I group, the mice received basic diet with intraperitoneal injection of CatS-I (1mg/kg·d); all animals were treated for 17 days. n=20 in each group. Hind limb ischemia model was established at 3 days after injection in both groups. Blood flow was measured by laser Doppler blood flow analyzer, the ratio of ischemic area to non-ischemic area was calculated; protein expressions of peroxidase proliferation activated receptors-γ (PPAR-γ), p-Akt, p-eNOS and VEGF were examined by Western blot analysis at day 4 after the operation; frozen section of ischemic skeletal muscle was taken at 7 days after operation to measure capillary density by immunohistochemistry.Results: ① CatS-I inhibited blood flow recovery. Compared with Control group, CatS-I group had slower blood flow recovery in ischemic hind limb, P<0.05. ② CatS-I inhibited capillary formation. At 14 days after operation, capillary formation in non-ischemic skeletal muscles was similar between 2 groups, P>0.05; while in ischemic skeletal muscles, capillary density was lower in CatS-I group than Control group, P<0.01. ③ Compared with Control group, CatS-I group showed decreased protein expressions of PPAR-γ, p-Akt, p-Enos and VEGF, P<0.05. Conclusions: CatS-I regulated ischemia-induced neovascularization might be related to PPAR-γ activation and PI3K/Akt/eNOS signaling pathway in experimental mice.