Effects Of Diammonium Glycyrrhizinate On The Expression Of TLR-4 And NF-κB In Rat’s Kidney With Acute Kidney Injury Induced By Paraquat

Objective To investigate the protective effects of diammonium glycyrrhizinate (DG) in rat’s kidney with acute kidney injury induced by paraquat(PQ) poisoning, To study the relative to effects of rat’s kidney and TLR-4,Myd88, NF-κB and and the molecular mechanisms. And to explore it’s protective effects and mechanisms, on kidney with acute kidney injury inducedMethods Fifty SD rats were divided into three groups by table of random number:paraquat group (PQ group), glycyrrhizin diammonium intervention group (DG group) and control group (NS group). There were 20 rats in PQ group,20 in DG group and 10 in NS group. The paraquats(100mg/kg) were administered by gavage in the PQ group and the DG group, while the NS group with the same dose of saline. Then immediately,the glycyrrhizin diammonium(50mg/kg/24h) were administered by intraperitoneal injection in the DG group, while the same dose of saline were injected in the PQ group and NS group. Then,the rats which were observed to 72 hours after administration were sacrificed. The blood of abdominal aortic were used to assess renal function. Morphological changes of renal tissue were observed by pathologica way. The ELISA assay was applyed to measure the IL-6 of kidneys and blood. And the protein expressions of TLR-4,Myd88 and NF-κB P65 were examined by Immunohistochemistry. The gene expressions of TLR-4,Myd88 and NF-κB on kidneys were detected by QR-PCR.Results The levels of serum Cr,BUN and IL-6 of the DG group were lower than those in the PQ group (P<0.01), while they were higher than the NS group(P<0.01). The pathomorphological observation showed that the renal organizational structure was clear and there were no significant pathological changes of edema, congestion, degeneration in the NS group,. While swelling, vacuolar degeneration,necrosis, luminal stenosis and atresia were seen in the PQ group and the DG group, and lesions in the DG group were lighter than the PQ group. The results of Immunohistochemistry confirmed that TLR4 is mainly expressed in the kidney cell membrane, Myd88 expressed in the cytoplasm, mainly, and NF-κB P65 expressed mainly in the nucleus, rarely in the cytoplasm. The expressions of the three factors were mainly expressed in renal tubular epithelial cells and glomerulus mesangial cell. And the expressions of those in the DG group were stronger than the NS group(P<0.01) but were weaker than the PQ group (P<0.01). The results of PCR demonstrated that the expressions of TLR-4mRNA, myd88mRNA and NF-KBmRNA in DG group were stronger than those in the NS group(P<0.01) but were weaker than the PQ group (P <0.01).Conclusions The paraquat can induce acute kidney injury in rat in which the injury of renal tubular epithelial cells is the most serious. And the expressions of TLR-4mRNA, Myd88 mRNA, NF-κB mRNA, IL-6 were significantly increased in the rats with paraquat poisoning. Diammonium Glycyrrhizinate can alleviate acute kidney injury caused by paraquat poisoning, and the mechanisms may be associated with the decreaseing expressions of TLR-4,Myd88 and NF-κB.