Objective:

2

To investigate the effects of Tongxinluo (TXL) on thromboangiitis obliterans (TAO) and the underlying mechanisms.

Methods:

2

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:

2

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:

2

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.