关键词: 补体 C5a / C5aR 通路, 纤维介素蛋白-2 凝血酶原酶, 肾癌, 高凝状态

Abstract: Objective To investigate the relationship between the activation of complement C5a / C5aR pathway and tumor hypercoagulability and the underlying mechanism in renal carcinoma bearing mice. Methods The cancer and paracancerous tissues of 32 patients with renal cell carcinoma diagnosed by pathological biopsy in the Tangshan People’s Hospital from July 2016 to October 2019 were obtained. The expression levels of C5a / C5aR pathway activation related proteins in tissues were detected by Western blotting. The human ACHN renal cancer cells were inoculated subcutaneously in the axillary region of the BALB / c-nu / nu nude mice. After successful inoculation, they were randomly divided into intervention group and model group, in which the intervention group was injected with C5aR antagonist (C5aRA) via the tail vein, and the model group was injected with normal saline in equal volume, and 6 mice with no subcutaneous inoculation and no C5aRA treatment were taken as the control group. The tumor growth was observed and the levels of hypercoagula bility related indexes were measured. The mice were sacrificed to collect cancer tissues, and the expression levels of C5a / C5aR pathway activation related proteins were detected by Western blotting. Results The tumor volume of mice in the two groups was statistically significant in 6 ~ 21 day, and the tumor volume of the intervention group was significantly lower than that of the model group (P< 0. 05). There was no significant difference in serum D-D, vWF and TF levels in the first day of tumor-bearing mice in the three groups. The serum coagulation index levels in the intervention group and the model group were significantly increased at the 14th day and the 21st day. Moreover, the serum coagulation index levels in the intervention group were significantly lower than those in the model group (P< 0. 05). The expression levels of C5aR, C5b-9, FGL2, P38 and p-P38 in mice cancer tissues in the intervention group were significantly lower than those in the model group ( P < 0. 05). The expression levels of C5aR, C5 b-9, FGL2, P38 and p-P38 in renal carcinoma were significantly higher than those in adjacent tissues (P< 0. 05). There were 14 cases of hypercoagulability and 18 cases of non-hypercoagulability in 32 cases of renal carcinoma. The expression levels of C5aR, C5 b-9, FGL2, P38 and p-P38 in hypercoagulable group were significantly higher than those in non-hypercoagulable group (P< 0. 05). Conclusion Complement C5a / C5aR pathway can induce hypercoagulability of renal carcinoma by regulating the expression of FGL2, and then participate in the pathogenesis of renal carcinoma.

Key words: complement C5a / C5aR pathway, fibrinogen-like protein2, renal cell carcinoma, hypercoagulability