Effects of Liuwei Dihuang Decoction on urine protein and glomerular p-p38 MAPK,α-actinin-4,and synaptopodin in mice with adriamycin nephropathy
Objective To investigate the intervention effects of Liuwei Dihuang Decoction(LWDHD)on urine protein in mice with adriamycin nephropathy(ADRN)and its possible mechanism.Methods Five of 30 SPF-grade male C57BL/6 mice were randomly selected as the blank group,and the remaining mice were injected with adriamycin(0.01 g·kg-1)via the tail vein to replicate the ADRN model.Two weeks later,the successfully modeled mice were randomized into the model group,the benazepril group,and the low-,medium-,and high-dose LWDHD groups,with 5 mice in each group.The blank and model groups were given an equal volume of water for injection by gavage.The benazepril group was given 0.001 3 g·kg-1 benazepril by gavage,while the low-,medium-,and high-dose LWDHD groups were given 9.75,19.5,and 39 g·kg-1 LWDHD by gavage respectively,once a day for 8 consecutive weeks.Automatic biochemical analyzer was used to check the 24-hour urine protein quantification,and the serum levels of albumin,creatinine,and potassium in mice.HE staining and electron microscopy were used to observe renal pathological changes and foot process morphology.Immunohistochemistry and Western blot were used to examine the expressions of phosphorylated p38 MAPK(p-p38 MAPK),α-actin-4,and synaptopodin proteins in mice kidneys.RT-PCR was used to examine the expressions of α-actin-4 and synaptopodin mRNA in mice kidneys.Results Compared with the blank group,the body weight,24-hour urine volume,and serum albumin level of the model group decreased,while the 24-hour urine protein quantification increased(P<0.05);hyperplasia of glomerular mesangial cells,partial mesangial area expansion,renal tubular protein casts,and interstitial inflammatory cell infiltration were observed,with extensive fusion of foot processes;the expressions of α-actinin-4 protein and mRNA,and p-p38 MAPK protein increased(P<0.05),while the expressions of synaptopodin protein and mRNA decreased(P<0.05).Compared with the model group,the pathological changes and foot process fusion in each intervention group were improved to varying degrees.The quantitative reduction of 24-hour urine protein was observed in the benazepril group as well as the medium-and high-dose LWDHD groups.The expression of p-p38 MAPK protein decreased in the high-dose LWDHD group(P<0.05),while the expressions of synaptopodin protein and mRNA increased in the low-,medium-,and high-dose LWDHD groups(P<0.05).There was no statistically significant difference in various indicators among benazepril group and the low-,medium-,and high-dose LWDHD groups(P＞0.05).Conclusion LWDHD may relieve renal pathological changes and foot process fusion,alleviate foot cell damage,and reduce urine protein in mice with ADRN,by inhibiting the activation of the p38 MAPK pathway and upregulating the protein and mRNA expressions of α-actin-4 and synaptopodin.
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