Study on ulinastatin alleviating the nephritis injury in hemorrhagic shock rats by regulating the TLR4/NF-κB signaling pathway via miR-146a

ObjectiveTo investigate the effects of ulinastatin on the miR-146a and TLR4/NF-κB signaling pathways based on sodium acetate Ringer's solution to further weaken the inflammatory damage of renal tissue in hemorrhagic shock rats.

MethodsThe hemorrhagic shock model in 24 healthy SD rats were established, and divide into the shocked non-resuscitation group(SR group, n=8), sodium acetate Ringer's solution resuscitation group(AR, n=8) and ulinastatin combined with sodium acetate Ringer's solution resuscitation group(UR, n=8).The mRNA expression levels of miR-146a and inflammatory factors(TNF-α, IL-1, IL-4, IL-6 and IL-10) in the kidney tissue in three group were detected using the real-time quantitative PCR technology, the expression levels of TLR4 and NF-κB protein were detected using Western blot, and the pathological changes of the kidney tissues of rats in each group were observed under light microscope.

ResultsCompared with the SR group, the expression levels of miR-146a mRNA in the renal tissues of the AR group and UR group significantly increased(P < 0.01), and compared with the AR group, the expression level of miR-146a mRNA in the UR group increased(P < 0.01).Compared with the SR group, the expression levels of TNF-α mRNA in the AR group and UR group significantly decreased(P < 0.01), while the expression level of TNF-α mRNA in the UR group still significantly decreased compared with the AR group(P < 0.01).Compared with the SR group, the expression levels of IL-1 and IL-6 mRNA in the AR group and UR group significantly decreased(P < 0.01), and there was no statistical significance in the expression levels of IL-1 and IL-6 mRNA between the UR group and AR group(P>0.05).Compared with the SR group and AR group, the expression levels of IL-4 and IL-10 mRNA in the UR group significantly increased(P < 0.01), and the differences of those between SR group and AR group were not statistically significant(P>0.05).Compared with the SR group, the expression levels of TLR4 and NF-κB protein in the AR group and UR group significantly decreased(P < 0.01).Compared with the AR group, the expression levels of TLR4 and NF-κB protein in the UR group still significantly decreased(P < 0.01).Under the light microscope, compared with the SR group, the pathological damage degree of kidney tissue in the AR group and UR group significantly alleviated, and the relieving degree of kidney tissue injury in UR group was more significant than that in AR group.

ConclusionsUlinastatin may play a further protective role on the basis of sodium acetate Ringer's solution alleviating the inflammatory injury of renal tissue in rats with traumatic hemorrhagic shock, and the mechanism of which may be related to the up-regulation of miR-146a, inhibition of the TLR4/NF-κB signaling pathway and regulation of the expression of inflammatory factors.