Objective： To evaluate the pharmacodynamic differences of various oral preparations of Panax Notoginseng Saponins （PNS） on acute blood stasis model rats， and to compare them with commercially available Xueshuantong Capsules （XST） and Sanqitongshu Capsules （SQTS）.

Methods

2

Based on the previous studies， five different oral preparations of PNS including PNS phospholipid complex enteric capsules （PNS-PC）， PNS pH-dependent solid dispersions （PNS-SD）， PNS self-double-emulsifying enteric capsules （PNS-SDEDDS）， PNS bioadhesive microsphere enteric capsules （PNS-BMS）， and N-acetyl-L cysteine modified PNS bioadhesive microsphere enteric capsules （PNS-NAC-BMS） were prepared. Eighty SD rats were randomly divided into the Control group， model （AD） group， XST+AD group， SQTS+AD group， PNS+AD group， PNS-PC+AD group， PNS-SD+AD group， PNS-SDEDDS+AD group， PNS‑BMS+AD group， PNS-NAC-BMS+AD group， 8 rats in each group. The rats in drug administration groups were given the appropriate dose of drug by gavage according to the body mass and drug loading capacity， and the rats in Control and AD groups were given blank capsule by gavage. After 7 d of drug administration， the acute blood stasis model was established in rat by injection of epinephrine hydrochloride combined with ice bath. On the following day， the tongue images and sublingual veins of the rats were photographed to evaluate the tongue condition scores； the tail vein blood was collected to record the tail vein coagulation time； the abdominal aorta blood was collected， and the levels of blood rheological indexes （including whole blood viscosity at different shear rates， Carson’s viscosity， plasma viscosity）， four indexes of coagulation ［including activated partial thromboplastin time （APTT）， prothrombin time （PT）， thrombin time （TT）， fibrinogen （FIB）］， and plasma endothelin （ET）， endothelial-type nitric oxide synthase （eNOS）， 6-keto-prostaglandin F1α （6‑keto-PGF1α） were detected.

Results

2

①Compared with the Control group， the rats in AD group had whitish tongue， purple-black sublingual blood vessels， higher tongue condition score （

P

<

0.001）， shorter tail vein coagulation time （

P

<

0.001）， higher levels of whole blood viscosity at different shear rates， Carson's viscosity， and plasma viscosity （

P

<

0.001）， shorter APTT， PT， and TT （

P

<

0.001）， higher levels of FIB and ET （

P

<

0.001）， and lower levels of eNOS and 6-keto-PGF1α （

P

<

0.001）. ②Compared with the AD group， the tongue condition scores of all administration groups were significantly decreased （

P

<

0.001，

P

<

0.01）. Compared with the XST+AD group and the SQTS+AD group， the tongue condition scores of the PNS-PC+AD group， PNS-SDEDDS+AD group， PNS-BMS+AD group and PNS‑NAC-BMS+AD group were also significantly de

creased （

P

<

0.05）. ③Compared with the AD group， the tail vein coagulation time of the PNS-PC+AD group， PNS-SDEDDS+AD group， PNS-BMS+AD group， PNS-NAC-BMS+AD group， the PNS+AD group， XST+AD group and SQTS+AD group was obviously prolonged （

P

<

0.001，

P

<

0.01，

P

<

0.05）. Compared with the XST+AD group and SQTS+AD group， the tail vein coagulation time of the PNS-PC+AD group， PNS-SDEDDS+AD group， PNS-BMS+AD group， and PNS-NAC-BMS+AD group was also obviously prolonged （

P

<

0.05）. ④Compared with the AD group， the levels of whole blood viscosity， Carson’s viscosity and plasma viscosity in the five self-prepared PNS oral preparation groups were significantly decreased （

P

<

0.001，

P

<

0.01）， and the levels of whole blood viscosity in the XST+AD group， SQTS+AD group and PNS+AD group， the Carson's viscosity in the XST+AD group， and the plasma viscosity in the PNS+AD group were also decreased （

P

<

0.01，

P

<

0.05）. Compared with the XST+AD group and SQTS+AD group， the whole blood viscosity level of the PNS-PC+AD group was also decreased （

P

<

0.05）. Compared with the SQTS+AD group， the levels of Carson's viscosity in the PNS-PC+AD group， PNS-BMS+AD group and PNS-NAC-BMS+AD group were decreased （

P

<

0.05）. ⑤Compared with the AD group， the APTT and TT were significantly prolonged （

P

<

0.001，

P

<

0.01，

P

<

0.05）， and the FIB levels were significantly reduced （

P

<

0.01） in all administration groups， and the PT was also significantly prolonged in the PNS-PC+AD group， PNS-SDEDDS+AD group， PNS‑BMS+AD group and PNS-NAC-BMS+AD group （

P

<

0.001，

P

<

0.01）. Compared with the XST+AD group and SQTS+AD group， the PT and TT were significantly prolonged （

P

<

0.05） and the levels of FIB were significantly decreased （

P

<

0.01） in the PNS-PC+AD group， PNS‑SDEDDS+AD group， PNS-BMS+AD group and PNS-NAC-BMS+AD group. ⑥Compared with the AD group， the ET levels were significantly decreased （

P

<

0.001，

P

<

0.05） and the levels of eNOS and 6-keto-PGF1α were significantly increased （

P

<

0.001，

P

<

0.01，

P

<

0.05） in all administration groups. Compared with the XST+AD group and the SQTS+AD group， the levels of ET were significantly decreased （

P

<

0.01） and the levels of eNOS were significantly increased （

P

<

0.05） in the PNS-PC+AD group， PNS-SDEDDS+AD group， PNS-BMS+AD group and PNS-NAC-BMS+AD group， the levels of 6-keto-PGF1α were significantly increased in the PNS-PC+AD group， PNS-SD+AD group， PNS-SDEDDS+AD group， PNS-BMS+AD group， and PNS-NAC-BMS+AD group （

P

<

0.01）.

Conclusion

2

The five self-prepared PNS oral preparations， as well as the APIs and XST and SQTS can effectively improve the blood stasis status in rats of acute blood stasis model. While the PNS-PC， PNS-SDEDDS， PNS-BMS and PNS-NAC-BMS are superior to the commercially available two positive medicines and APIs for the improvement of the various indexes related to blood stasis in rats， which have a better prospect for application.