天马颗粒剂通过TLR4/NF-κB/Klotho途径调控大肠癌裸鼠移植瘤研究

Study on Tianma Granule Regulating Colorectal Cancer Model byTLR4/NF-κB/Klotho Pathway

目的:观察天马颗粒剂对大肠癌裸鼠移植瘤组织中TLR4、NF-κB、Klotho表达的影响。方法:以SPF级裸鼠为研究对象,通过皮下种植HCT116细胞株构建裸鼠移植瘤模型,随机分为3组:对照组、天马颗粒低剂量组、天马颗粒正常剂量组,对照组予生理盐水20 mL/kg,天马颗粒低剂量5.39 g/kg;天马颗粒正常剂量10.79 g/kg;灌胃给药,隔天1次,持续2周。摘除肿瘤组织,测量肿瘤体重及体积,免疫组化检测TLR4、NF-κB、Klotho表达量。结果:同对照组相比,天马颗粒正常剂量组肿瘤组织中TLR4、NF-κB表达降低,Klotho表达明显增加(P<0.05);天马颗粒正常剂量组与天马颗粒低剂量组相比,肿瘤组织中TLR4、NF-κB表达未见明显差异(P>0.05),Klotho表达升高(P<0.05)。结论:天马颗粒剂可抑制TLR4/NF-κB通路活性,促进Klotho表达,降低肿瘤中炎性因子表达,改善肿瘤炎症微环境。

Objective:To observe the effect of Tianma granule on the expression of TLR4,NF-κB and Klotho in nude mice with colorectal cancer.Methods:SPF nude mice were used as the research object,and HCT116 cell line was subcutaneously planted to construct a nude mouse xenograft model.The nude mice were randomly divided into three groups:control group,Tianma granuLe low-dose group and Tianma granule normal-dose group.The control group was given normal saline 20mL/kg,Tianma granuLe low-dose 5.39g/kg;tianma granuLe normal dose 10.79 g/kg;intragastric administration,once every other day for 2 weeks.The tumor tissues were removed,and the tumor weight and volume were measured.The expression of TLR4,NF-κB and Klotho was detected by immunohistochemistry.Results:Compared with the control group,the expression of TLR4 and NF-κB in the tumor tissue of the normal dose group of Tianma granuLes decreased,the expression of Klotho increased significantly(P<0.05),and the expression of Klotho increased(P<0.05).Conclusion:Tianma granuLes can inhibit the activity of TLR4/NF-κB pathway,promote the expression of Klotho,reduce the expression of inflammatory factors in tumors,and improve the inflammatory microenvironment of tumors.