The Study On The Influense Of Earthworm Component On P38MAPK,NF-κB Of Unilateral Ureteral Obstruction Rats

Objective:To investigate the effect of earthworm component serine hydrolase on p38mitogen-actived protein kinase signaling pathway and nuelear factork kappa B of unilateral ureteralobstruction rats.and to illustrate the mechanism of the components of earthworm serine hydrolase on delaying renal interstitial fibrosis.Method:Copy the model of renal interstitial fibrosis in rats with unilateral ureteral obstructi on.The60male wistar rats were randomly divided into four groups:sham-operation group(12),UUO group (16), earthworm of low-dose group (16),earth worm of high-dose group (16). Earthworm of low-dose group was given the earthworm component of serine proteolytic enzymes capsules0.24g·kg-1·d-1to gavage.Earthworm of high-dose group was given the earthworm component of serine proteolytic enzymes capsules0.48g·kg-1·d-1to gavage.Sham operation group and UUO group were given the same dose of distilled water.6rats of each group were killed respectively at the2,4weeks after surgery.Put to death the day after the collection of24h urine detection of24urinary protein excretion, executed the same day to collect blood for serum creatinine (Scr),blood urea nitrogen(BUN)index detection. Take the obstructed kidney tissue specimens.HE staining under the light microscope to observe the pathological changes.The pathological changes and expression of TGF-β1,a-SMA and Col-IV in renal interstitium were observed.Western blot analysis the protein expression of NF-κ B and p38MAPK in renal tissue.Results:(1) From the appearance point of view, treatment group of the earthworm in the corresponding time points of the obstructed kidney enlargement and stagnant water level were lighter and more red color than the UUO group.(2) Rats in each group at different time points24hours urinary protein excretion was no significant difference (p>0.05)(3)Scr and BUN levels of Earthworm groups were lower than UUO group at the2,4weeks after surgery (p<0.05. p<0.01).The same time.Scr and BUN level of Earthworm of low-dose group were lower than Earthworm high-dose group.(4) Immunohistochemical results showed:the expressions of TGF-β1,a-SMA and Col-Ⅳ in renal tissue of UUO group and Earthworm groups increased gradually, with the extension of the time of obstruction. In the corresponding point in time,Earthworm of high-dose group and low-dose group compared with UUO group, TGF-beta1,a-SMA and Col-Ⅳ protein expression were significantly lower(p<0.05, p<0.01).(5) Western blot showed:the expressions of NF-κB and p38MAPK gradually increased with the extension of the time of obstruction in UUO group and earthworm groups. The expressions of NF-κB and p38MAPK were significantly lower than that of UUO group at the corresponding time point in earthworm groups(p<0.05).(6) Earthworm low-dose group was better than the high dose group to slow down the development of renal interstitial fibrosis.Conclusion:(1) The earthworm component could improve renal function of UUO rats through reducing serum creatinine,blood urea nitrogen level.(2) The earthworm component could reduce renal fibrosis degree(3) The earthworm component could delay the Progression of renal interstitial fibrosis,through decreasing the expressions of TGF-βl,a-SMA,Col-IV in UUO kidney tissue.(4) The earthworm component may be slow down the development of renal interstitial fibrosis, through the many targets blocking TGF-β1→p38MAPK→NF-κ B signaling pathways.