文献类型：期刊文献

中文题名：基于TLR4/NF-κB/TGF-β1信号通路探讨蛭龙通络胶囊在阿霉素肾病大鼠抗肾纤维化中的作用

英文题名：Effects of Zhilong Tongluo capsule on renal fibrosis in rats with adriamycin-induced nephropathy through the TLR4/NF-κB/TGF-β1 signaling pathway

作者：李旭萍[1];马鸿斌[1];马海兰[1]

第一作者：李旭萍

机构：[1]甘肃中医药大学附属医院肾病科,兰州730000

第一机构：甘肃中医药大学第二附属医院

年份：2024

卷号：44

期号：6

起止页码：488

中文期刊名：现代免疫学

外文期刊名：Current Immunology

收录：CSTPCD

基金：甘肃省中医药管理局科研课题重点项目(GZK-2019-30)。

语种：中文

中文关键词：肾间质纤维化;阿霉素;蛭龙通络胶囊;Toll样受体;核因子κB;转化生长因子β1

外文关键词：renal interstitial fibrosis;adriamycin;Zhilong Tongluo capsule;toll-like receptor;nuclear factorκB;transforming growth factorβ1

摘要：为探讨蛭龙通络胶囊抑制阿霉素(adriamycin,ADR)肾病大鼠肾纤维化的作用机制,右肾摘除及多次尾静脉注射3 mg/kg ADR构建肾纤维化大鼠模型,建模成功后将实验鼠分为模型组和蛭龙通络胶囊组、蛭龙通络胶囊+激活剂组,另选未处理大鼠为空白对照组。蛭龙通络胶囊组大鼠给予蛭龙通络胶囊混悬液灌胃,蛭龙通络胶囊+激活剂组大鼠给予蛭龙通络胶囊混悬液灌胃和LPS(5 mg/kg)腹腔注射,空白对照组、模型组大鼠给予等量生理盐水处理,给药共持续8周。观察各组大鼠一般情况并记录体质量(body weight,BW)变化,采用尿蛋白定量试剂盒以及ELISA检测试剂盒检测24 h尿蛋白(24 h urine protein,24 h UPO)、肌酐(creatinine,Cr)和血尿素氮(blood urea nitrogen,BUN)含量;断头处理大鼠后取肾组织,制备切片行马松(Masson)染色观察肾组织纤维化情况;qRT-PCR法和免疫组化染色检测各组大鼠肾组织中TLR4、NF-κB和TGF-β1的mRNA及蛋白表达水平。结果显示,与空白对照组比较,模型组大鼠BW下降,肾组织胶原纤维面积占比(collagen proportionate area,CPA)、24 h UPO、Cr、BUN水平升高,TLR4、NF-κB、TGF-β1的mRNA及蛋白表达量显著升高(均P<0.05)。与模型组比较,蛭龙通络胶囊组大鼠BW增加,CPA、24 h UPO、Cr、BUN水平降低,TLR4、NF-κB、TGF-β1的mRNA及蛋白表达量显著降低(均P<0.05)。与蛭龙通络胶囊组比较,蛭龙通络胶囊+激活剂组大鼠BW显著下降,CPA、24 h UPO、Cr和BUN水平升高,TLR4、NF-κB、TGF-β1的mRNA及蛋白表达量显著升高(均P<0.05)。由此,蛭龙通络胶囊或通过抑制TLR4/NF-κB/TGF-β1信号通路表达,改善肾病大鼠肾组织纤维化,减轻肾损伤。
Aiming to explore the underlying mechanism of Zhilong Tongluo capsule on protecting rats with adriamycin(ADR)-induced nephropathy from renal fibrosis,renal fibrosis rat model was established by right side nephrectomy and multiple caudal vein injections of 3 mg/kg ADR.After successful model establishment,rats were divided into model group,Zhilong Tongluo capsule group and Zhilong Tongluo capsule+activator group,and rats without treatment were used as control.Rats in Zhilong Tongluo capsule group were gavaged with Zhilong Tongluo capsule suspension,rats in Zhilong Tongluo capsule+activator group were additionally intraperitoneally injected with LPS(5 mg/kg),and rats in blank control group and model group were treated with same volume of saline.All treatments lasted for 8 weeks.The general conditions of rats and body weight(BW)changes were recorded.The 24 h urine protein(24 h UPO),creatinine(Cr),and blood urea nitrogen(BUN)were detected by urine protein quantification kit and ELISA kit.The rats were sacrificed and then renal tissues were collected for pathological study.The fibrosis of renal tissues was observed after Masson staining.The mRNA and protein levels of TLR4,NF-κB,and TGF-β1 were measured by qRT-PCR and immunohistochemistry.Compared to that of the blank control group,BW was decreased,while the collagen proportionate area(CPA),24 h UPO,Cr,and BUN were increased in the model group.The mRNA and protein levels of TLR4,NF-κB,and TGF-β1 were also significantly increased(all with P<0.05).Compared to those of the model group,the BW of rats was increased,and CPA,24 h UPO,Cr,and BUN were decreased in the Zhilong Tongluo capsule group.The mRNA and protein levels of TLR4,NF-κB,and TGF-β1 were significantly decreased(all with P<0.05).Compared to those of the Zhilong Tongluo capsule group,the BW was decreased,CPA,24 h UPO,Cr,and BUN were increased in the Zhilong Tongluo capsule+activator group while the mRNA and protein levels of TLR4,NF-κB,and TGF-β1 were all significantly increased(all with P<0.05).In conclusion,Zhilong Tongluo capsule may mitigate fibrosis of renal tissues and alleviate renal damage by inhibiting the expression of the TLR4/NF-κB/TGF-β1 signaling pathway.