Abstract:Objective To explore the therapeutic effect of sodium tanshinone ⅡA sulfonate injection（STSI）on lower limb deep vein thrombosis（DVT）based on NF-κB p65 signaling pathway. Methods A total of 70 SD rats were randomly divided into the normal group，model group，sham group，low -dose STSI group，medium -dose STSI group，high -doseSTSI group，and positive drug group，with 10 rats in each group，respectively. Except for the normal group and sham group，the DVT rat model constructed using the modified Reyers method in other groups . Starting from the first day of successful model buliding，and the normal group，sham group，and model group were given equal volumes of normal saline intraperitoneal injection，and the STSI groups were given 12.5 mg/kg，25 mg/kg，and 50 mg/kg STSI，respectively，while the positive drug group was given 50 mg/kg sodium aescinate injection once a day. After 7 days of administration，the rats were anesthetized and euthanized. The femoral vein（FV）tissues of each group were collected and paraffin embedded. After slicing，HE staining was used to observe the infiltration of inflammatory cells in each group. RT -PCR and western blot were used to detect the expression of mRNA and protein of tumor necrosis factor-α（TNF-α），interleukin- 6（IL-6），and inter cellular adhesion molecule-1（ICAM-1）. Results HE staining results showed that a large amount of inflammatory exudate was found in the FV tissue of the model group. The vascular wall was thinned，and the thrombus had infiltrated into the tissues. In the middle - dose STSI group，inflammatory exudation was significantly reduced compared to the model group and sham group，with vascular smooth muscle cells and morphology remaining intact，andthe number of inflammatory cells was comparable to that in the positive drug group. RT - PCR and western blot results showed that the mRNA and protein expressions of p65 in the model group and sham group were obviously upregulated compared to the normal group（P<0.05）. Compared with the model group，the mRNA and protein expression of p65 in the STSI groups obviously decreased（P<0.05），while mRNA and protein expression of p65 in the positive drug group was comparable to that in the middle-dose STSI group（P>0.05）. The protein expression levels of TNF-α，IL-6 and ICAM-1in rats were up-regulated in the order of normal group，sham operation group and model group（P<0.05），and the mRNA expression levels of TNF-α were also up-regulated in the order of normal group，sham operation group and model group（P<0.05）. Compared with the model group，the protein and mRNA expressions of TNF-α，IL-6，ICAM-1 in the STSI groups were significantly reduced（P<0.05），and those in the positive drug group were comparable to the middle-dose STS group（P>0.05）. Conclusion STSI can effectively improve the inflammatory response of DVT rats，which may be related to its regulation of NF-κB signaling pathway mediated expression of NF-κB p65. Although the positive expression of p65mRNA and protein could serve as reference indicators for NF -κB p65 pathway activation，the lack of direct evidence demonstrating pathway activation represents a limitation in this study，which needs to be addressed in future experiments.