Objective

2

To investigate the effect and mechanism of

Ziyu Ointment

（紫榆膏） on postoperative incisional pain and inflammatory response by regulating stromal cell-derived factor-1 （SDF-1）/C-X-C chemokine receptor type 4 （CXCR4） pathway.

Methods

2

Eighty Sprague-Dawley （SD） rats were randomly divided into control group， model group， and low-， medium-， a

nd high-dose

Ziyu Ointment

groups， with 16 rats in each group. Except for the control group， the postoperative incisional pain model was established using the Brenan method. After successful modeling， the low-， medium-， and high-dose

Ziyu Ointment

groups were treated with

Ziyu Ointment

at different doses （10 mg/kg， 20 mg/kg， and 50 mg/kg） applied to the wound， while the control group and model group were treated with an appropriate amount of sterile normal saline applied to the wound， once a day for 2 consecutive weeks. After the intervention， changes in pain behavior of rats in each group at different time points were measured， including the mechanical paw withdrawal threshold （MPWT）， thermal paw withdrawal latency （TPWL）， and cumulative pain score. Hematoxylin-Eosin （HE） staining was used to observe the histopathological changes of rat skin tissue. TUNEL assay was employed to detect the apoptotic rate of skin tissue cells. Enzyme-Linked Immunosorbent Assay （ELISA） was used to determine the levels of inflammatory factors including interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） in rat serum. The expression of SDF-1/CXCR4 signaling pathway proteins was analyzed by Western Blot and immunohistochemical staining.

Results

2

HE staining showed that the skin tissue of rats in the model group had inflammatory cell infiltration， incomplete structure， and rare newly formed capillaries. Compared with the model group， the low-， medium-， and high-dose

Ziyu Ointment

groups had increased damaged newly formed capillaries and reduced inflammatory cell infiltration in the skin tissue. Compared with the control group， the apoptotic rate of skin tissue cells， the protein levels of SDF-1 and CXCR4， and the serum levels of IL-1β， IL-6， and TNF-α in the model group significantly increased （

P

＜0.05）. Compared with the model group， the apoptotic rate of skin tissue cells， the protein levels o

f SDF-1 and CXCR4， and the serum levels of IL-1β， IL-6， and TNF-α in all

Ziyu Ointment

groups significantly decreased （

P

＜0.05）. Compared with the control group at the same time points， the MPWT and TPWL of the model group significantly decreased， and the cumulative pain score significantly increased on the 3rd， 5th， 7th， and 15th day after operation （

P

＜0.05）. Compared with the model group at the same time points， the MPWT and TPWL of all

Ziyu Ointment

groups significantly increased， and the cumulative pain score significantly decreased on the 3rd， 5th， 7th， and 15th day after operation （

P

＜0.05）. The improvement of the above indicators in the high-dose

Ziyu Ointment

group was superer to that in the medium- and low-dose

Ziyu Ointment

groups （

P

＜0.05）.

Conclusion

2

Ziyu Ointment

can reduce postoperative incisional pain and inhibit the secretion of inflammatory factors in rats. This effect may closely relate to the regulation of SDF-1/CXCR4 signaling pathway.