| Previous studies showed that Rhizoma Polygonatum,a traditional Chinese medicine,had a better protective effect on experimental kidney injury in mice.In order to explore the effective part of its function,this experiment used Polygonatum sibiricum polysaccharides(PSP),the main active ingredient of Rhizoma Polygonatum,as a test drug to study its protective effect on gentamicin-induced renal injury in rats.Sixty SD rats were randomly divided into 6 groups:blank group,model group,low,medium and high doses of Polygonatum sibiricum polysaccharides groups(0.25、0.5、1 g/kg),and Jinkui Shenqi Pills group(0.6 g/kg).Except that the blank group rats were injected with normal saline,the other groups were intramuscularly injected with gentamicin injection(100 mg/kg).Six hours after the injection,different doses of PSP,Jinkui Shenqi Pill and distilled water were administered intragastrically.The procedure was repetead for 7 continuous days.At the end of the experiment,the rat blood and kidney tissue samples were collected.Serum CRE and UREA levels were detected by biochemical method,renal histological changes were observed by HE staining,NGAL,KIM-1,IL-1β,IL-6,TNF-α and p38 MAPK genes expression in renal tissues were detected by qRT-PCR,and p38 MAPK,p-p38 MAPK and p-ATF2 proteins expression were detected by Western Blot method.The results show:(1)Changes in body weight and renal organ coefficient:Compared with the blank group,the weight of the model group decreased significantly(P<0.05),and the renal organ coefficient increased significantly(P<0.05).Compared with the model group,the weight of PSP medium dose groups increased significantly(P<0.05),and the body weight of PSP low,high dose group and Jinkui Shenqi Pills group increased,but the difference was not significant(P>0.05).Three dosages of PSP and Jinkui Shenqi Pills group significantly reduce the renal organ coefficient in rats(P<0.05).The renal organ coefficient of PSP medium dose group was significantly lower than that in the Jinkui Shenqi Pillsgroup(P<0.05).(2)Blood biochemical indicators of renal function:Compared with the blank group,the serum CRE and UREA levels in the model group were significantly increased(P<0.05);Compared with the model group,the levels of CRE and UREA in the three PSP groups and Jinkui Shenqi Pills group were significantly lower(P<0.05).The levels of CRE and UREA of PSP medium dose group were significantly lower than that in the Jinkui Shenqi Pills group(P<0.05).(3)Histological changes of kidney:In the model group,the renal tubular epithelial cells were swollen and degenerated with vacuolized cytoplasms.A large number of inflammatory cells infiltrated,and part of the structure disappeared with glomerular degeneration and necrosis.After intragastric administration of PSP and Jinkui Shenqi Pills,renal tubular epithelial cells were slightly swollen,the degree of necrosis was significantly reduced,a small amount of inflammatory cell infiltrated and glomerular degeneration and necrosis were significantly improved.(4)The genes expression of NGAL,KIM-1 in renal tissues:Compared with the blank group,the expression of NGAL and KIM-1 genes in the renal tissue of the model group were significantly increased(P<0.05).Compared with the model group,the three PSP dose groups and Jinkui Shenqi Pills group significantly reduced the expression of NGAL and KIM-1 genes(P<0.05).The genes expression levels of NGAL and KIM-1 of PSP medium dose group were significantly lower than that in the Jinkui Shenqi Pills group(P<0.05).(5)Expression of IL-1β,IL-6,TNF-α and p38 MAPK genes in renal tissues:Compared with the blank group,the expression of IL-1β,IL-6,TNF-α and p38 MAPK in the renal tissue of the model group were significantly increased(P<0.05).Compared with the model group,expression of the four genes in the three PSP dose groups and Jinkui Shenqi Pills group were significantly decreased(P<0.05).The genes expression levels of IL-1β,IL-6,TNF-α and p38 MAPK of PSP medium dose group were significantly lower than that in the Jinkui Shenqi Pills group(P<0.05).(6)Expression of p38 MAPK,p-p38 MAPK and p-ATF2 proteins in renal tissues:Western Blot results showed that the proteins expression of p38 MAPK,p-p38 MAPK and p-ATF2 in the model group were significantly higher than that in the blank group.Compared with the model group,the expression of p38 MAPK,p-p38 MAPK and p-ATF2 in the three PSP dose groups and Jinkui Shenqi Pills group were decreased in different degrees.In summary,PSP can significantly reduce serum CRE and UREA levels in rats with gentamicin-induced renal injury,alleviate renal histopathological lesion,reduce the expression of NGAL and KIM-1 genes in renal tissues,and inhibit p38 MAPK/ATF2 signaling pathway and the production of TNF-α,IL-1β and IL-6.It indicated that PSP has better anti-kidney damage effect.This study can provide a reference for the prevention and treatment of animal kidney injury in veterinary clinics. |
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