The Effect of Regulating miR-223 Expression on the Expression of Inflammatory Factors and Renal Interstitial Fibrosis in a Rat Model of Chronic Glomerulonephritis and its Relationship with the IL-6/STAT3 Signaling Pathway

Objective: To explore the effect of miR-223 on the expression of inflammatory factors and renal interstitial fibrosis in a rat model of chronic glomerulonephritis based on the interleukin 6/signal transducer and activator of transcription 3(IL-6/STAT3) signaling pathway. Methods: A total of 70 SPF-grade healthy adult male SD rats were selected, and were randomly divided into five groups. Except for the blank group, the remaining four groups of rats were all subcutaneously injected with 1 mg/m L cationized bovine serum albumin(C-BSA) emulsion at multiple points(in the first week) and injected with 2.5 mg/m L C-BSA solution through the tail vein(from the 2nd to 4th week) to establish a glomerulonephritis model. After successful modeling, the blank group and the modeling group were injected with normal saline through the tail vein, the negative control group was injected with 50 μg/kg NC agomir through the tail vein, the miR-223 agonist group was injected with 50 μg/kg miR-223 agomir through the tail vein, and the pathway activation group was injected with 50 μg/kg miR-223agomir and 1 μg/kg rh IL-6 through the tail vein. After continuous treatment for 21 d,the rats were sacrificed and kidney tissues were taken. The expression of miR-223, inflammatory factors and IL-6/STAT3 signaling pathway-related proteins in the five groups of rats was observed and compared, and the renal interstitial fibrosis in the five groups of rats was also observed and compared. Results: The relative expression level of miR-223 in the blank group was significantly higher than that in the other four groups. The relative expression levels of miR-223 in the miR-223 agonist group and the pathway activation group were significantly higher than those in the model group and the negative control group(P<0.05). The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the blank group were lower than those in the other four groups. The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-1β, IL-17, TNF-α,and TGF-β1 in the pathway activation group were higher than those in the miR-223agonist group(P<0.05). The proportion of renal interstitial fibrosis area in renal tissue of the blank group was significantly lower than that in the other four groups. The proportion of renal interstitial fibrosis area in renal tissue of the model group and the negative control group was higher than that in the miR-223 agonist group and the pathway activation group. The proportion of renal interstitial fibrosis area in renal tissue of the pathway activation group was higher than that in the miR-223 agonist group(P<0.05).The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the blank group were lower than those in the other four groups. The expression levels of IL-6/GAPDH and pSTAT3/STAT3 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the pathway activation group were higher than those in the miR-223 agonist group(P<0.05). Conclusion: The expression of inflammatory factors and renal interstitial fibrosis in rats with chronic glomerulonephritis are affected by miR-223. The mechanism may be related to the expression of IL-6/STAT3 signaling pathway-related proteins.