| Objective:This paper, by animal experiments, was to investigate the effects of Shizao Decoction and Shizao Decoction mixed with licorice on the function of kidney and small intestine of rats and their chronic toxicity from histomorphology, in order to improve the safety coefficient of the decoction and explore whether its toxicity will increase while combing with licorice in clinic, thus providing scientific experimental data for future clinical medication safety and enhancing the improvement and development of TCM theory. Method:90 SPF SD rats(45 male and 45 female) were randomly divided into seven groups: high, medium and low-dose groups of Shizao Decoction(HSD, MSD, LSD, 13 rats of each group), high, medium and low-dose groups of Shizao Decoction mixed with licorice(HSDL, MSDL, LSDL, 13 rats of each group) and a normal control group(NCG, 12 rats). They were conventionally bred in cage. One week later, the rats of each dose group were given intragastric administration of crude drug(2ml/100g) with equal concentration and different volume. The concentration of the high, medium and low-dose group were respectively 0.28 g, 0.14 g and 0.07 g /(kg?d). The normal group was given intragastric administration of equal volume of distilled water. The intragastric administration was given routinely at 8:00, observing and making records about rats, weighing them 2-3 times each week and adjusting the amount of intragastric administration according to their weights. The intragastric administration was given 6 days a week, altogether 90 days. After the last intragastric administration, food and water were not given to the rats for 24 hours. Over a half of rats of each group were randomly selected to collect blood from abdominal aorta for blood routine and blood biochemical indicators. Visual observation was made to the kidney and small intestine of rats and organizational structure changes were observed by light microscope. The rest rats were observed for 14 days, repeating above procedure. Statistical software SPASS20.0 were used for the analysis of the experimental data, P <0.05 being considered statistically significant. Results: 1 Impact on weightWeights of rats in each group before, during and after drug administration were not significantly different(P>0.05). 2 The impact on renal coefficientRenal coefficient of rats during the administrative period and the recovery period had no significant difference(P>0.05); compared with those during the administration, the renal coefficient of rats in each group during the recovery period had no significant difference(P>0.05). 3 Impact on the blood routine 3.1 Impact on the WBCCompared with normal control group, WBC of the rats during administration was decreased, being not statistically significant(P>0.05); WBC of rats in each group during the recovery period increased, being no significant difference(P>0.05) compared with the normal control group; compared with those during the administration, WBC rats in each group during the recovery period had no significant difference(P>0.05). 3.2 Effect on RBC, HGB and PLTCompared with those in the normal control group, RBC, HGB and PLT of rats during the administration and recovery periods had no significant difference(P>0.05); compared with those in the administration period, RBC, HGB and PLT of rats in each group during the recovery period had no significant difference. 4 Impact on renal function 4.1 Impact on CREACompared with the normal control group, CREA of rats in each group during the administration period was slightly increased, being not statistically significant(P>0.05); CREA of rats in each group during the recovery period by pairwise comparison had no significant difference(P>0.05); compared with the recovery period, the rats of each group during the recovery period had no significant difference(P>0.05). 4.2 Impact on BUNCompared with the normal control group, BUN of rats in LSDL group was significantly higher(P<0.05). The BUN of rest rats in each group were all increased, but being not statistically significant(P>0.05); the BUN of rats in each group during the recovery period by pairwise comparison had no significant difference(P>0.05); compared with the normal control group, BUN of rats during the recovery period had no significant difference(P>0.05).5 Impact on GLUCompared with those in the normal control group, GLU of rats during the administration and recovery periods had no significant difference(P>0.05); compared with those in the administration period, GLU of rats in each group during the recovery period had no significant difference. 6 The impact on renal histologyCompared with the control group, the boundaries of the renal medullary junction in rats during the administration period were basically clear, and the glomerular structure was normal. Glomus showed congestion and inflammatory cell infiltration to various degree. Glomerular atrophy could be seen in the LSD and LSDL groups. glomerular proliferation appeared in the MSDL group. Proximal tubule lumen tube of each group was normal and edema is visible in proximal tubule and distal tubule to various degrees, and renal medullary collecting tubules were normal. During the recovery period, glomerular structures of each group were normal; the boundaries between cortex and medulla were clear; glomus congestion situation had been improved significantly; inflammatory cells significantly reduced; edema of cell monolayer of the proximal tubule and the distal tubule had significantly reduced; and renal medullary collecting tubule structure was normal. Compared with the administration, conditions of rats in each group during the recovery period were all improved. 7 The impact on small intestineCompared with the control group, the small intestine of rats during the administration and recovery periods had no obvious abnormalities. Conclusion:1 There is no significant effect on weight gaining in rats for Long-term use of Shizao Decoction or Shizao Decoction mixed with licorice.2 There is no significant effect on RBC、HGB、PLT、GLU for rats long-term taking Shizao Decoction and Shizao Decoction mixed with licorice.3 Long-term using Shizao Decoction or Shizao Decoction mixed with licorice can affect WBC, i.e. the WBC showed a slight decrease, but it turned normally after stop administration.4 Long-term use of Shizao Decoction and Shizao Decoction mixed with licorice can affect CREA and BUN of rats, i.e. the performance of CREA, BUN increased, but it turns normally after stop administration.5 Long-term use of Shizao Decoction and Shizao Decoction mixed with licorice has some influence on rat kidney, showing varying degrees of change to glomus(hyperemia, hyperplasia, and atrophy), and proximal tubule edema, which will be improved during the recovery period.6 Long-term use of Shizao Decoction and Shizao Decoction mixed with licorice has no obvious damage to the small intestine in rats. |
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