摘要
目的基于肠肾轴理论及肠道TLRs/NF-κB信号转导通路探讨升清降浊胶囊的作用机制。方法SD大鼠随机分为正常组、假手术组、模型组及治疗组(升清降浊胶囊,1.2 g·kg^-1);建立5/6肾切除大鼠慢性肾衰竭模型;灌胃给药,每日1次,连续8周。给药结束后检测大鼠血肌酐、尿素、24 h尿蛋白定量;采用ELISA法测定大鼠血清硫酸吲哚酚(IS)、脂多糖(LPS)水平;Western Blot法测定大鼠肠黏膜紧密连接蛋白claudin-1、occludin、ZO-1的表达水平;qRT-PCR法检测肠道组织TLR2、TLR4、MyD88、NF-κB mRNA的表达水平。结果与假手术组比较,模型组大鼠的血肌酐、尿素、24 h尿蛋白定量、IS、LPS以及MyD88 mRNA表达水平明显升高(P<0.05),claudin-1、occludin、ZO-1蛋白表达以及TLR2、TLR4 mRNA表达水平明显下降(P<0.05)。与模型组比较,治疗组大鼠的血肌酐、尿素、24 h尿蛋白定量、IS、LPS以及MyD88、NF-κB mRNA表达水平明显下降(P<0.05),claudin-1、occludin、ZO-1蛋白表达以及TLR2、TLR4 mRNA表达水平明显升高(P<0.05)。结论升清降浊胶囊可降低5/6肾切除大鼠血液循环中的肠源性毒素LPS、IS,促进肠道屏障修复,可能与调控TLRs/NF-κB信号转导通路相关。
Objective To explore the mechanism of Shengqing Jiangzhuo capsule based on the theory of gut-kidney axis and intestinal TLRs/NF-κB signal transduction pathway.Methods Rat 5/6 nephrectomy models was used to establish the CRF model in rats.A normal group,a Sham operation group,a model group,and a Shengqing Jiangzhuo capsule treatment group were set up with intervention last for 8 weeks.After the intervention,the blood samples and the 24 hours urine were collected,and the ileum and colonic tissues were retained.The serum creatinine,urea,and 24 hours urine protein were compared.The serum levels of indoxyl sulfate(IS)and lipopolysaccharides(LPS)detected by ELISA were compared.The expression of tight junction protein claudin-1,occludin and ZO-1 in the intestinal mucosa were detected by Western Blot.Real-time PCR was carried out to detect mRNA expression of TLR2,TLR4,MyD88 and NF-κB in intestinal tissue.Results Compared with the Sham operation group,the serum creatinine,urea and 24 hour urine protein quantitation of the model group were significantly increased(P<0.05);the levels of IS and LPS,and expression of MyD88 mRNA were significantly increased(P<0.05);the contents of claudin-1,occludin and ZO-1 were significantly decreased(P<0.05);the expression of TLR2 and TLR4 mRNA was significantly decreased(P<0.05).Compared with the model group,the serum creatinine,urea and 24 hour urine protein quantitation of the treatment group were significantly decreased(P<0.05),the levels of IS and LPS were significantly decreased(P<0.05),the contents of claudin-1,occludin and ZO-1 were significantly increased(P<0.05),the expression of TLR2 mRNA was significantly increased(P<0.05),the expression of MyD88,NF-κB mRNA was significantly decreased(P<0.05).Conclusion Shengqing Jiangzhuo capsule can reduce intestinal toxins LPS and IS in the circulation of 5/6 nephrectomy rats,repair the intestinal barrier function.The mechanism may be through regulating the TLRs/NF-κB signal transduction pathway.
作者
黎志彬
王超
汤水福
张礼财
李林
林燕娜
LI Zhibin;WANG Chao;TANG Shuifu;ZHANG Licai;LI Lin;LIN Yanna(Nephrology Department,The Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2019年第11期1301-1306,共6页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
广东省自然科学基金项目（2015A030310150）
全国名老中医药专家洪钦国名医工作室建设基金资助项目
作者简介
黎志彬,男,博士,住院医师,研究方向:中医药防治肾脏疾病。Email:373025933@qq.com;通信作者:汤水福,男,主任医师,研究方向:中医药防治肾脏疾病。Email:tsf08@126.com。
