Study on Bone Density and TLR4 Signaling Pathway in IgA Nephropathy Rat Treated with Steroids
Objective:To explore the effects of glucocorticoid treatment on bone density change and TLR4 signaling pathway activity in IgA nephropathy rats.Methods:60 male SD rats of SPF grade,5-month old,mean weight of 185g were selected and randomly divided into 4 groups:control group,non-hormone group,low-dose hormone group,and high-dose hormone group,with 15 rats in each group.The IgA nephropathy model was replicated by gavage of bovine serum albumin+subcutaneous injection of CC14 and castor oil+tail vein injection of lipopolysaccharide,with 9 weeks.The non-hormone group received benazepril hydrochloride tablets(1.041 mg/kg/d),the low-dose hormone group received methylprednisolone 15 mg/kg/d,and the high-dose hormone group received methylprednisolone 30 mg/kg/d,continuously administered by gavage for 10 weeks until the end of experiment.Then to detect urine red blood cell count and 24-hour urine protein quantification,serum creatinine and urea nitrogen in each group.Bone density of femur was measured using dual energy X-ray absorption method.Bone trabecular microstructure parameters were scanned and calculated by micro-CT,including bone trabecular number,bone trabecular thickness,and volume fraction.Western blot method was to detect Toll like receptor 4(TLR4),myeloid differentiation factor(MyD88),and nuclear factor-KB(NF-κB)proteins in bone tissues.Results:All rats survived until the end of experiment.After treatment,the low-dose and high-dose hormone groups significantly reduced urinary red blood cell count,24-hour urine protein quantification,serum creatinine,and urea nitrogen,as well as bone density,trabecular number,trabecular thickness,and volume fraction.However,TLR4,MyD88,and NF-κB proteins significantly increased(P＜0.05).Conclusion:Glucocorticoid therapy for IgA nephropathy can improve clinical symptom and renal function,but at the same time,it reduces bone density and alters bone trabecular structure,which may be related to abnormal activation of TLR4 signaling pathway in bone tissues.
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