益生菌嗜黏蛋白阿克曼菌改善线粒体功能障碍调节慢性肾脏病大鼠肾小管上皮间充质转化  

Probiotic Akkermansia muciniphila improves mitochondrial dysfunction and regulate renal tubular epithelial⁃mesenchymal transition in rats with chronic kidney disease

作　　者：郭蕊蕊 袁晓英[2] 商晓晖 张明慧[1] 张红霞[2] GUO Rui-rui;YUAN Xiao-ying;SHANG Xiao-hui;ZHANG Ming-hui;ZHANG Hong-xia(Department of Nephrology,Shengli Oilfield Central Hospital,Dongying 257099,China;Blood Purification Center,Shengli Oilfield Central Hospital,Dongying 257099,China)

机构地区：[1]胜利油田中心医院肾内科,山东东营257099 [2]胜利油田中心医院血液净化中心,山东东营257099

出　　处：《解剖科学进展》2025年第1期42-46,共5页Progress of Anatomical Sciences

基　　金：东营市自然科学基金项目(2023ZR038)。

摘　　要：目的 探讨嗜黏蛋白阿克曼菌(AKK)对CKD大鼠肾损伤的改善作用及机制。方法 将SD大鼠随机分为假手术组(Sham组)、慢性肾脏疾病组(CKD组)、AKK治疗组(AKK组)和AKK治疗+LPS组(AKK+LPS组),每组10只,采用5/6肾切除法建立CKD模型。HE染色和Masson染色观察大鼠肾组织病理损伤和纤维化情况;Western blot方法检测大鼠肾组织EMT相关蛋白和TLR4/RAS/MAPK信号通路相关蛋白表达水平;ROS和JC-1荧光探针检测大鼠肾组织中ROS水平和线粒体膜电位变化;RT-qPCR检测大鼠肾组织中mtDNA拷贝数。结果 AKK改善CKD大鼠肾组织病理损伤和纤维化,增加肾组织中E-cadherin蛋白表达水平,降低Vimentin和α-SMA蛋白表达水平,降低肾组织ROS水平,增加肾组织mtDNA拷贝数和线粒体膜电位,下调肾组织中TLR4、AT1、ACE、p-ERK、p-JNK和p-P38蛋白表达水平;给予LPS逆转了AKK对CKD大鼠肾组织病理损伤和纤维化的改善作用,降低肾组织中E-cadherin蛋白表达水平并增加Vimentin和α-SMA蛋白表达水平,增加肾组织ROS水平并降低肾组织mtDNA拷贝数和线粒体膜电位,上调肾组织中TLR4、AT1、ACE、p-ERK、p-JNK和p-P38蛋白表达水平。结论 AKK治疗通过抑制TLR4/RAS/MAPK信号通路改善线粒体功能障碍,抑制肾小管EMT并改善肾间质纤维化,从而改善CKD诱导的肾损伤。Objective To explore the effect and mechanism of Akkermansia muciniphila(AKK)on renal injury in CKD rats.Methods SD rats were randomly divided into sham operation group(Sham group),chronic kidney disease group(CKD group),AKK treatment group(AKK group)and AKK treatment+LPS group(AKK+LPS group),with 10 rats in each group.CKD model was established by 5/6 nephrectomy.HE staining and Masson staining were used to observe the pathological damage and fibrosis of renal tissue of rats.Western blot was used to detect the expressions of EMT⁃related proteins and TLR4/RAS/MAPK signaling pathway⁃related proteins in renal tissues of rats.ROS and JC⁃1 fluorescent probes were used to detect the changes of ROS level and mitochondrial membrane potential in renal tissue of rats.RT⁃qPCR was used to detect the copy number of mtDNA in renal tissue of rats.Results AKK improved the pathological injury and fibrosis of kidney tissue in CKD rats,increased the expression of E⁃cadherin and decreased the expressions of Vimentin andα⁃SMA in kidney tissue,decreased the level of ROS in kidney tissue,increased the copy number of mtDNA and mitochondrial membrane potential in kidney tissue,and down⁃regulated the expressions of TLR4,AT1,ACE,p⁃ERK,p⁃JNK and p⁃P38 in kidney tissue.Administration of LPS reversed the improvement of AKK on renal pathological injury and fibrosis in CKD rats,decreased the expression level of E⁃cadherin and increased the expressionls of Vimentin andα⁃SMA in renal tissue,increased the level of ROS in renal tissue,decreased the copy number of mtDNA and mitochondrial membrane potential in renal tissue,and increased the expressions of TLR4,AT1,ACE,p⁃ERK,p⁃JNK and p⁃P38 in renal tissue of rats.Conclusion AKK treatment can improve mitochondrial dysfunction,inhibit renal tubular EMT and improve renal interstitial fibrosis by inhibiting TLR4/RAS/MAPK signaling pathway,thus improving CKD⁃induced renal injury.

关 键 词：嗜黏蛋白阿克曼菌 慢性肾脏病 线粒体功能障碍 上皮间充质转化 TLR4/RAS/MAPK信号通路 

分 类 号：R692[医药卫生—泌尿科学]