Correlation Between Inflammation And Tumor Hypercoagulability In Lymphoma-bearing Mice And Intervention Of Southern Snake Vine

Objection:By establishing a lymphoma-bearing Balb/C mouse model to observe the changes of inflammatory factors,coagulation indexes,immune indexes and platelet activation indexes in peripheral blood of tumor-bearing mice and the expression of tumor-associated macrophages in tumor,to study the relationship between the inflammatory microenvironment and the hypercoagulable state of the tumor,and to explore the therapeutic mechanism of the traditional Chinese medicine Celastrol in the treatment of lymphoma.Methods:1.In this study,Balb/C mice with normal immune function were used to establish the B cell lymphoma model.25 Balb/C mice aged 6-8 weeks were randomly divided into control group(n=5),tumor-bearing intervention group(n=10)and tumor-bearing non-intervention group(n=10).The mice were injected subcutaneously with 2×106/0.2 mL of 38B9 cells in the tumor-bearing group.The control group was injected subcutaneously with 0.2 mL PBS.On the 14th day of tumor bearing,MRI and B ultrasonography were performed to confirm the tumor formation.The intervention group was treated with Celastrol for 10 days.Mice were sacrificed timely if in the dying state and the tumor tissues were collected for HE and immunohistochemistry staining.2.On the 1st,14th and the 21th day,mice were taken blood from inner canthus vein.The serum levels of CRP,TNF-?,IL-6,IL-10,TF and vWF were measured by ELISA.3.The expression of Treg and B cells and the expression of platelet activation indexes such as P-selectin and GP? b?a in peripheral blood of mice were detected by flow cytometry.4.Immunohistochemistry was used to detect the expression of CSF-1R and CD68 in the tumor tissues of tumor-bearing mice.Results:1.The rate of tumor formation was 100%in Balb/C mice,and the pathological feature of tumor tissues showed the lymphoma cells diffused distribution with CD 19 highly expressed.2.After the tumor formation,compared with the tumor-bearing before,the levels of CRP,TNF-?and IL-6 in the tumor-bearing mice increased(P<0.05),while the level of IL-10 was decreased(P<0.05).The plasma levels of TF and vWF in tumor-bearing mice increased(P<0.05).To analyze the above indicators for relevance,the levels of CRP,TNF-a and IL-6 in peripheral blood were positively correlated with the levels of TF and vWF,and the level of IL-10 was negatively correlated with TF and vWF.3.Compared with the non-intervention group,the tumor growth of the mice in the intervention group was slow and the average survival time was prolonged(P<0.05),and the tumor weight and tumor volume were significantly smaller than those of the non-intervention group(P<0.05).The levels of proinflammatory cytokines such as CRP,TNF-a and IL-6 in the intervention group were decreased while the level of anti-inflammatory factor IL-10 was increased(P<0.05).The level of TF decreased(P<0.05),while vWF had a downward trend.The expression of CD41/CD62p was significantly decreased(P<0.05),while CD41/CD61 had no significant changes.The positive rates of CSF-1R and CD68 antigen in the tumor tissue of the intervention group were significantly lower than that of the non-intervention group(P<0.05).Conclusion:1.The model of B cell lymphoma-bearing Balb/C mouse was successfully established.2.The inflammatory factors in lymphoma are closely related to the hypercoagulable state of the tumor.3.Celastrol can effectively interfere with the process of tumor by reducing the secretion of inflammatory factors,improving the immunoinflammatory microenvironment and controlling the hypercoagulable state.