Objective

2

To observe the long-term safety of Zhenwutang on blood indexes and histopathology in SD rats.

Method

2

The acute toxicity test was conducted to evaluate the acute toxicity of Zhenwutang toward SD rats. The SD rats were randomly assigned into 4 groups （low-， medium-， and high-dose Zhenwutang and control group）， with 32 rats （16 males and 16 females） in each group. The rats were administrated once daily with Zhenwutang respectively at the doses of 16， 24， and 36 g·kg

-1

（equal to 20， 30， 45 times of clinical dose） for 30 days， and those in the control group with purified water. After administration， the rats were observed for another 14 days. The body weight and food intake were measured once a week and the dosage was changed according to the body weight. General observation was carried out once a day during the experiment period. The electrocardiogram （ECG） was measured a day before administration （D

-1

）， 4 h after administration （D

0

）， on day 15 of administration （D

14

）， and at the end of administration （D

29

） and the end of recovery period （D

43

）. At the end of administration （D

30

） and the end of recovery period （D

44

）， the blood assay and histopathological examinations were performed for 64 rats.

Result

2

Compared with control group，some rats in zhenwutang high-dose group （D

8

-D

35

）， medium-dose group （D

13

-D

35

） and low-dose group （D

15

-D

33

） showed depilation， mainly in the neck.Compared with the control group， rat body weight of D

7

in Zhenwutang medium-dose and high-dose groups had significantly decreased，rat body weight of D

21

and D

29

in Zhenwutang low-dose group had decreased too.During D

7

-D

29

， body weight of rats in Zhenwutangn medium-dose and high-dose groups had differently decreased.Compared with control group， food intake in Zhenwutang low-dose， medium-dose and high-dose groups had significantly reduced in the first week. The food intake of male rats in Zhenwutang medium-dose and high-dose groups had significantly decreased in the first， second and fourth week .Compared with control group， the heart rate of female rats in Zhenwutang medium-dose and high-dose groups had increased. In the D

14

and D

29

days， the heart rate of male rats in Zhenwutang low-dose， medium-dose and high-dose groups had increased. The P wave time of male rats in Zhenwutang medium-dose group have prolonged. The QRS interval of female rats in Zhenwutang medium-dose and high-dose groups had prolonged. After 14 days of administration， the s-wave amplitude of Zhenwutang high-dose group had significantly decreased. After D

14

and D

29

days of administration， the s-wave amplitude of Zhenwutang in middle and high dose groups had significantly decreased.This study showed that intragastric administration of Zhenwutang for 30 days caused hair loss， weight loss， poor appetite， increased heart rate， and irregular heart rate of SD rats. It had little effect on the hematological indicators and did not cause obvious changes in pathological and blood indicators.

Conclusion

2

Zhenwutang exerts positive inotropic effect， and 45 times of the clinical dose has no obvious toxic effect. However， attention should be paid to preventing the occurrence of ventricular premature beat.