肾癌荷瘤小鼠组织中补体C5a/C5aR通路活化与肿瘤高凝状态的关系及其机制研究  

Relationship between Activation of Complement C5a/C5aR Pathway and Tumor Hypercoagulability in Renal Carcinoma-bearing Mice

作　　者：陈超[1] 常娜[2] 赵萌 张蕊 李博[3] CHEN Chao*;CHANG Na;ZHAO Meng;ZHANG Rui;LI Bo(Department of Pathology y Zunhua Peopled Hospital,Zunhua,Hebei,064200,China;Department of Radiotherapy and Chemotherapy,Tangshan People's Hospital,Tangshan,Hebei,063000,China;Department of Pharmacy,Tangshan People's Hospital,Tangshan,Hebei,063000,China)

机构地区：[1]遵化市人民医院病理科,河北省遵化市064200 [2]唐山市人民医院放化五、唐山市肿瘤放射治疗学重点实验室,063000 [3]唐山市人民医院药剂科,河北省唐山市063000

出　　处：《医学分子生物学杂志》2022年第2期140-144,170,共6页Journal of Medical Molecular Biology

摘　　要：目的研究肾癌荷瘤小鼠组织中补体C5a/C5aR通路活化与肿瘤高凝状态的关系及其机制。方法收集2016年7月至2019年10月于唐山市人民医院收治的32例经病理学活检确诊的肾癌患者的癌组织和癌旁组织。采用Western印迹法检测组织中C5a/C5aR通路活化相关蛋白表达情况。于BALB/c-nu/nu裸鼠前肢腋窝皮下接种人ACHN肾癌细胞株,接种成功后随机分为干预组、模型组,其中干预组尾静脉注射C5a联合C5aR阻断剂(C5aR antagonist,C5aRA),模型组等体积注射生理盐水,另取6只空白小鼠作为对照组。观察小鼠肿瘤生长情况,检测高凝状态相关指标水平。脱颈处死小鼠,收集癌组织,采用Western印迹法检测组织中C5a/C5aR通路活化相关蛋白表达情况。结果两组小鼠肿瘤体积于荷瘤6~21 d差异具有统计学意义,且干预组的肿瘤体积明显低于模型组(P<0.05)。3组小鼠于荷瘤第1天的血清D-D、vWF、TF水平差异无统计学意义,荷瘤第14天、第21天干预组、模型组血清凝血指标水平明显增加,其中干预组均明显低于模型组(P<0.05)。干预组癌组织中C5aR、C5b-9、FGL2、P38、p-P38的表达水平均明显低于模型组(P<0.05)。肾癌患者癌组织中C5aR、C5b-9、FGL2、P38、p-P38的表达水平均明显高于癌旁组织(P<0.05)。32例肾癌患者中高凝状态患者14例,非高凝状态患者18例,高凝状态组癌组织中C5aR、C5b-9、FGL2、P38、p-P38的表达水平均明显高于非高凝状态组(P<0.05)。结论补体C5a/C5aR通路可通过调控FGL2的表达而诱导肾癌的高凝状态,进而参与肾癌的发病过程。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

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 

分 类 号：R73-354[医药卫生—肿瘤]