Protective Effects Of Berberine On High-fat Diet Induced Chronic Kidney Injury And Relative Mechanisms’ Research

Background Metabolic syndrome (MS) is a clinical syndrome characterized with acomplex metabolic disorder, including hypertension, hyperglycemia, hyperlipidemia,insulin resistance etc. Chronic kidney injury is closely associated with metabolicsyndrome. Hyperlipidemia, one important component in MS, not only aggravatesvarious kinds of kidney diseases, but also directly induces kidney injury. IKK/NF-κBsignaling pathway is a major inflammatory signal transduction pathways. Thestimulation of the lipid activates IKK/NF-κB pathway, then actives NF-κB, andthrough the scecretion of inflammatory cytokines causes the damage to the cells.Berberine (BBR) depended on its unique pharmacological effects has become aresearch hotspot in recent years. But how to reasonably apply berberine in thetreatment of chronic kidney disease (CKD) is worth exploring.Methods Feeding C57BL/6mice with a high-fat diet was an available way toinvestigate metabolic syndrome. In order to explore the protective effect of berberineand the related mechanisms’, we established the animal models of mice chronickidney injury and observed the changes of serum lipids, renal function, renal tissuemorphology and the expression of inflammatory and fibrosis factors in each groups.We fed C57BL/6mice with high-fat diet to induce chronic kidney injury. Then themice of model group were intragasticed150mg/kg·d berberine dissolved in1%carboxymethylcellulose sodium (CMCC-Na) for six weeks after animal modelsestablished. At the end of the experiment, blood and kidney tissue were collected.Blood was for dectecting urine volume, urinary albumin, total cholesterol,triglyceride, cystamin C, serum creatinine and urea nitrogen. Pathological changeswere observed by light microscope by HE staining. Expression of phosphorylatedIKKβ, phosphorylated IKKε, phosphorylated p65, phosphorylated p50, inflammatoryfactors (IL-1β, iNOS) were detected by Western Blot. Expression of F4/80and iNOSwere detected by immnofluorescence staining staining and immunohistochemistry respectively. Then the ratio of mcrophage-positive in the section of kidney wascalculated.Results The research shows that six weeks’ treatment of berberine (150mg/kg·d) isable to effectively improve the renal abnormalities, including elevating renal function,ameliorating renal morphology, reducing the infiltration of mononuclear macrophages,inhibiting the expression of pIKKβ, pIKKε, phosphorylated p65, phosphorylated p50and inflammatory factors. These protecive effects may regulated by NF-κB signalingpathway.Conclusions Berberine may through the NF-κB signaling pathway to reduce theinfiltration of mononuclear macrophages, especially the M1mononuclearmacrophages, suppress the inflammatory reaction and then further ameliorate themice chronic kidney injury induced by high-fat diet. The research provides a novelaprroach and theoretical basis for the treatment for kidney diseases associated withmetabolic syndrome.