Objective

2

To observe the therapeutic effect of Changyanning Tablets on colorectal adenoma-carcinoma （CRA-CRC） model rats and explore its possible mechanisms.

Methods

2

Six rats were randomly assigned to the normal group （Normal）. The remaining rats were intraperitoneally injected with 1，2-dimethylhydrazine （DMH） at 60 mg/kg once a week for 15 weeks to establish the CRA-CRC model. In the 7th week， the model rats were randomly divided into five groups according to a randomized block design： a model group （Model）， a berberine group （HLS）， a low dose group of Changyanning Tablets （L-CYN）， a medium dose group of Changyanning Tablets （M-CYN）， and a high dose group of Changyanning Tablets （H-CYN）， with 6 rats in each group. From the 7th week of modeling， the HLS group was given berberine at 0.027 g/kg by gavage， while the L-CYN， M-CYN， and H-CYN groups were given Changyanning Tablets at 0.3， 0.6， and 1.2 g/kg by gavage， respectively. The Normal and Model groups were given distilled water by gavage. The above drug treatments were performed once daily for 8 weeks. General conditions， body weight， abdominal anatomical structure， incidence of intestinal tumors， pathological changes in intestinal tumor tissues， vascular endothelial growth factor （VEGF） protein expression in colorectal tissues， and cleaved Caspase-3 expression were compared among the groups.

Results

2

By the 15th week of modeling， compared with the Normal group， the Model group had a lower body weight （

P

<

0.05）. No significant difference in body weight was observed in the HLS， L-CYN， M-CYN， and H-CYN groups compared with the Model group （

P

>

0.05）. The Model group showed a large amount of ascites. No obvious organ abnormalities or tumor metastasis were observed in the abdominal cavity of rats in any group. Compared with the Normal group， the Model group had a shorter colorectal length （

P

<

0.05） and a higher number of tumors （

P

<

0.01）. Compared with the results in the Model group， the colorectal length in the H-CYN group was longer （

P

<

0.05）， and the number of tumors was lower in the HLS， H-CYN， and M-CYN groups （

P

<

0.05）， with one rat in the H-CYN group showing no visible tumors. Tumor size was larger in the Model group than in the Normal group （

P

<

0.01）， and smaller in the HLS， H-CYN， and M-CYN groups （

P

<

0.01）. The Model group showed significant increases in gland and cell numbers in the colon， extensive inflammatory cell infiltration between cells， dense cell arrangement， and significant changes in tumor cell size and morphology， including large and deeply stained nuclei， frequent nuclear division， and focal glandular severe atypical hyperplasia， high-grade intraepithelial neoplasia， and focal in situ carcinoma formation. In the L-CYN group， goblet cells disappeared， cells proliferated and were closely arranged

， with obvious nuclear division and numerous small nucleoli. The HLS and M-CYN groups had similar pathological results， including lymph follicle hyperplasia， glandular repair-like changes， crypt abscesses， and focal reduction of inherent glands. The H-CYN group had more organized gland arrangement， focal inflammatory cell infiltration， erosion， and focal reduction of inherent glands， with occasional nuclear division. The Model group had an incidence of adenocarcinoma of 50% and tubular adenoma of 33.3% （with mild and moderate atypical hyperplasia）， and one rat with severe atypical hyperplasia. All rats were successfully modeled. The pathological changes in intestinal tumor tissues in the L-CYN group were not significantly improved， whereas the HLS， M-CYN， and H-CYN groups showed reduced tumor tissue lesions， with the H-CYN group showing the most significant effect. Compared with the results in the Model group， VEGF protein expression was lower in the L-CYN group， though not statistically significant （

P

>

0.05）， and significantly lower in the HLS， M-CYN， and H-CYN groups （

P

<

0.05）. Cleaved Caspase-3 protein expression was lower in the colorectal tissues of the Model group than that in the Normal group （

P

<

0.05）. Cleaved Caspase-3 protein expression was higher in the colorectal tissues of the Chinese medicine treatment groups and the HLS group than that in the Model group （

P

<

0.05，

P

<

0.01）.

Conclusion

2

Changyanning Tablets can improve clinical symptoms and pathological changes in the colorectal mucosa of CRA-CRC model rats， and its mechanism may be related to the negative regulation of VEGF expression and the promotion of cleaved Caspase-3 expression.