慢性肾脏病肠道菌群失调的病理机制、治疗策略及中药的干预作用

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1、慢性肾脏病肠道菌群失调的病理机制、治疗策略及中药的干预作用［摘要］令C道菌群失调是中、晚期慢性肾脏病进展至尿毒症的高危因素之一，其特征就是益生菌减少、能产生尿毒素的条件致病菌增多。“肠-肾轴”学说和“慢性肾脏病-结肠轴概念的核心观点认为，失调的肠道菌群通过加剧尿毒素蓄积和诱导全身性微炎症反应等途径加重肾脏的损伤。初步的临床试验和动物实验的结果显示，以乳酸菌和双歧杆菌制剂为代表的益生菌和以菊粉、低聚半乳糖为代表的益生元，还有鲁比前列酮、活性炭吸附剂等都可以针对CKD患者体内失调的肠道菌群，通过减轻尿毒素蓄

2、积和抑制全身性微炎症反应等途径而改善肾功能。不仅如此，一些经口服或肠道给药的单味中药、中药复方还有中药提取物在一定程度上也能调节肠道细菌，保护肠道上皮屏障，减轻尿毒素蓄积，延缓CKD进展。其中，大黄类经方一一大黄甘草汤改善肾衰竭动物模型体内尿毒素蓄积的靶点不是肾脏，而可能是“肠道菌群所启动的肠-肾轴”。基于此，针对中、晚期CKD患者肠组织中肠道菌群相关的病理因素的干预性研究可能是今后的重点发展方向之一。［关键词］肠道菌群；中药；慢性肾脏病；肠-肾轴；病理机制[Abstract]Thegutmicrobi

3、otadysbiosisisoneoftheriskfactorsintheprogressionfromtheadvancedchronickidneydiseasetouremia,characterizedbythereductionofprobioticsandtheincreaseofopportunisticpathogensincludingurease-relatedmicrobes，endotoxin-relatedmicrobesandtoxin-relatedmicrobes，wh

4、ichcanproduceuremictoxins.Accordingtothecorepointof“thegut-kidneyaxis”theoryand“thechronickidneydisease-colonicaxis”concept，thegutmicrobiotadysbiosisaggravatesrenaldamagebyaccumulatinguremictoxinsandinducingthesystemicmicro-inflammation.Thepreliminarycli

5、nicaltrialsandanimalexperimentsshowthattheprobioticsbiologicalsfromLactobacillusacidophilusorBifidobacterium，andtheprebioticsincludinginulinandgalactooligosaccharides,aswellaslubiprostoneandactivatedcarbonadsorbentscanbeusedforimprovingdysfunctionofCKDpa

6、tientswiththegutmicrobiotadysbiosisviareducinguremictoxinsandinhibitingthesystemicmicro-inflammation.Butnotonlythat，itisreportedthat,tosomeextent，anumberofthesingleChineseherbalmedicine，theCHMprescriptionsandtheCHMextractswithoralorenemaadministrationcan

7、alsoregulatethegutmicrobiotadysbiosis，protecttheintestinalepithelialbarrier，reduceuremictoxinsaccumulationanddelayCKDprogression.Thereinto，DahuangGancaoDecoction，aclassicalCHMprescriptionofrhubarb，canameliorateuremictoxinsaccumulationintheanimalmodelswit

8、hrenalfailureprobablythroughtargetingthegut-kidneyaxistriggeredfromgutmicrobiota,butnottargetingthekidney.Basedontheseresults，theinterventionalstudiestargetingthegutmicrobiota-relatedpathologicalfactorssuchastightjunctionp