Objective:To investigate the influences of asiaticoside(AS)on inflammatory response and oxidative stress in rats with mesangial proliferative glomerulonephritis(MsPGN)by regulating the rat sarcoma(Ras)/extracellular signal regulated kinase(ERK)/mitogen activated protein kinase(MAPK)signaling pathway.Methods:Sixty SPF SD rats were randomly divided into sham operation group(Sham group),MsPGN model group(Model group),low-dose AS group(AS-L group,40 mg/kg),high-dose AS group(AS-H group,80 mg/kg),high-dose AS+Ras/ERK/MAPK signaling pathway activator group(AS-H+anisomycin group,80 mg/kg AS+10 mg/kg anisomycin),with 12 rats in each group.Rat model of MsPGN was established by modified serum immunization.The 24 h urine protein content of rats in each group was detected by Coomassie brilliant blue method.HE staining and PSA staining were used to observe the pathological changes of renal tissue of rats in each group.TUNEL staining was used to detect apoptosis of rat glomerular cells in each group.Levels of serum creatinine(Scr),superoxide dismutase(SOD),blood urea nitrogen(BUN),malondialdehyde(MDA),and levels of IL-18,IL-1β,TNF-α,SOD and MDA in renal tissues were measured by ELISA.Protein levels of Ras,p-ERK1/2,ERK1/2,MAPK and p-MAPK in renal tissues of rats in each group were detected by Western blot.Results:①AS alleviated inflammatory reaction and oxidative stress injury in MsPGN rats.Compared with Sham group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in model group were significantly increased(P<0.05),while SOD level in serum and renal tissue was significantly decreased(P<0.05).HE staining showed that the glomerulus of rats had severe mesangial hyperplasia,a large amount of matrix deposition,and the basement membrane was significantly thickened.Compared with model group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in AS-H group rats were significantly decreased(P<0.05),while SOD level in serum and renal tissue was significantly increased(P<0.05),HE staining showed alleviated mesangial hyperplasia injury.②AS downregulated the Ras/ERK/MAPK signaling pathway.Compared with Sham group,expression of Ras protein and phosphorylation level of ERK1/2 and MAPK in Model group were significantly increased(P<0.05);compared with Model group,expression of Ras protein,phosphory-lation level of ERK1/2 and MAPK in AS-H group were significantly decreased(P<0.05),and anisomycin reduced the inhibitory effect of AS on inflammatory response and oxidative stress injury in MsPGN rats(P<0.05).Conclusion:AS may reduce the inflammatory re-action and oxidative stress injury in MsPGN rats by down-regulating Ras/ERK/MAPK signaling pathway.

Objective:To investigate the influences of asiaticoside(AS)on inflammatory response and oxidative stress in rats with mesangial proliferative glomerulonephritis(MsPGN)by regulating the rat sarcoma(Ras)/extracellular signal regulated kinase(ERK)/mitogen activated protein kinase(MAPK)signaling pathway.Methods:Sixty SPF SD rats were randomly divided into sham operation group(Sham group),MsPGN model group(Model group),low-dose AS group(AS-L group,40 mg/kg),high-dose AS group(AS-H group,80 mg/kg),high-dose AS+Ras/ERK/MAPK signaling pathway activator group(AS-H+anisomycin group,80 mg/kg AS+10 mg/kg anisomycin),with 12 rats in each group.Rat model of MsPGN was established by modified serum immunization.The 24 h urine protein content of rats in each group was detected by Coomassie brilliant blue method.HE staining and PSA staining were used to observe the pathological changes of renal tissue of rats in each group.TUNEL staining was used to detect apoptosis of rat glomerular cells in each group.Levels of serum creatinine(Scr),superoxide dismutase(SOD),blood urea nitrogen(BUN),malondialdehyde(MDA),and levels of IL-18,IL-1β,TNF-α,SOD and MDA in renal tissues were measured by ELISA.Protein levels of Ras,p-ERK1/2,ERK1/2,MAPK and p-MAPK in renal tissues of rats in each group were detected by Western blot.Results:①AS alleviated inflammatory reaction and oxidative stress injury in MsPGN rats.Compared with Sham group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in model group were significantly increased(P<0.05),while SOD level in serum and renal tissue was significantly decreased(P<0.05).HE staining showed that the glomerulus of rats had severe mesangial hyperplasia,a large amount of matrix deposition,and the basement membrane was significantly thickened.Compared with model group,24 h urine protein content,glomerular cell apoptosis rate,serum Scr,BUN,MDA levels,renal tissue IL-18,IL-1β,TNF-α,MDA levels in AS-H group rats were significantly decreased(P<0.05),while SOD level in serum and renal tissue was significantly increased(P<0.05),HE staining showed alleviated mesangial hyperplasia injury.②AS downregulated the Ras/ERK/MAPK signaling pathway.Compared with Sham group,expression of Ras protein and phosphorylation level of ERK1/2 and MAPK in Model group were significantly increased(P<0.05);compared with Model group,expression of Ras protein,phosphory-lation level of ERK1/2 and MAPK in AS-H group were significantly decreased(P<0.05),and anisomycin reduced the inhibitory effect of AS on inflammatory response and oxidative stress injury in MsPGN rats(P<0.05).Conclusion:AS may reduce the inflammatory re-action and oxidative stress injury in MsPGN rats by down-regulating Ras/ERK/MAPK signaling pathway.