Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table: the
sham group,
TAO model group, Compound Danshen
Tablet (CDT) group, and the high-, medium-, and low-dose TXL groups. All mice except the
sham group were injected with
sodium laurate (0.1 mL, 5 mg/mL) in the femoral artery to establish
TAO mouse model. After modeling, mice in the
sham and
TAO model groups were intragastrically administered 0.5% (w/v)
sodium carboxymethylcellulose, mice in the CDT group were intragastrically administered 0.52 g/kg CDT, and mice in the TXL-H, TXL-M, and TXL-L groups were intragastrically administered 1.5, 0.75, and 0.38 g/kg TXL, respectively. After 4 weeks of gavage, the recovery of blood flow in the lower limbs of mice was detected by
Laser Doppler Imaging. The pathological changes and
thrombosis of the femoral artery were observed by morphological examination. The expressions of
tumor necrosis factor α (TNF-α) and
inducible nitric oxide synthase (iNOS) in the femoral artery wall were detected by HE staining. Levels of
thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α),
endothelin-1 (ET-1),
interleukin (IL)-1β and
IL-6 were measured using
enzyme-linked
immunosorbent assay (ELISA). Levels of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and
fibrinogen (FIB) were detected by a fully automated biochemical analyzer.
RESULTS: TXL promoted the restoration of blood flow in the lower limbs, reduced the area of
thrombosis in the femoral artery, and alleviated the pathological changes in the femoral artery wall. Moreover, the levels of TXB2, ET-1,
IL-6, IL-1β, TNF-α and iNOS were significantly lower in the TXL groups compared with the model group (P<0.05 or P<0.01), while the level of 6-keto-PGF1α was significantly higher (P<0.01). In addition, APTT, PT, and TT were significantly prolonged in TXL groups compared with the model group (P<0.05 or P<0.01), and FIB levels were significantly decreased compared with the model group (P<0.01).
CONCLUSIONS: TXL had a protective effect on
TAO mice, and the mechanism may involve inhibition of
thrombosis and inflammatory responses. TXL may be a potential
drug for the treatment of
TAO.