Protective effect of Shenbining Granule on renal tissue of IgA nephropathy rats based upon SphK1/S1PR2 pathway
OBJECTIVE To explore the effect and mechanism of Shenbining Granule(SG)on renal injury in rats with IgA nephropathy(IgAN)through sphingosine kinase 1(SphK1)/sphingosine 1 phosphate receptor 2(S1PR2)pathway.METHODS A total of 54 healthy male Sprague-Dawley rats were randomized into 5 groups of blank(n=10),model(n=10),prednisone(n=10),low-dose SG(n=12)and high-dose SG(n=12).Except for blank group,IgAN model was established in the other four groups.Treatment groups received intragastric dosing from Week 9.After 7 weeks,serum creatinine(SCr),blood urea nitrogen(BUN),alanine aminotransferase(ALT),serum albumin(ALB),urinary erythrocyte count and 24-hour urinary protein quantity(24 h-UTP)were measured.Renal pathological changes were observed by hematoxylin-eosin(HE)stain and IgA deposition was detected by immunofluorescence.The protein expressions of SphK1 and S1PR2 were examined by Western blot and the expressions of SphK1 and S1PR2 mRNA by real-time fluorescent quantitative polymerase chain reaction(RT-PCR).RESULTS As compared with blank group,urinary erythrocyte count,the levels of 24 h-UTP,SCr and BUN spiked signifi-cantly in model group(P＜0.01 or P＜0.05).The level of ALB dropped obviously(P＜0.01)while the level of ALT rose.However,no significant difference existed between model and blank groups(P＞0.05).There was obvious renal pathological injury.Massive IgA deposition could be detected by immunofluorescence.The expression levels of SphK1,S1PR2 protein and mRNA jumped sharply in renal tissue(P＜0.01).As compared with model group,urinary erythrocyte count,the levels of 24 h-UTP and BUN declined obviously in prednisone,low-dose SG and high-dose SG groups(P＜0.01),ALB level became mark-edly elevated(P＜0.01)while ALT level declined.The differences were not statistically significant(P＞0.05).SCr level declined markedly in low-dose SG group(P＜0.05).Renal pathology improved and IgA fluorescent deposition diminished.The expressions of SphK1,S1PR2 protein and mRNA dropped significantly in renal tissue(P＜0.01).CONCLUSION SG may lower urinary protein,lessen hematuria and improve renal function in IgAN rats through an inhibition of SphK1/S1PR2 pathway.Thus it protects kidney and prevents renal damage.
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