| In recent years,the heavy metal pollution problems have aroused people's wide concern,especially the cadmium pollution problem.Cadmium can cause liver,kidney,bone,testis tissues and other organs damage of human and animal.However,there is still a lack of effective drugs for the treatment of cadmium poisoning.Traditional Chinese medicine thinks that the nephrotoxicity which induced by cadmium is deficiency of kidney and blood stasis syndrome,therefore,we study the herbals of tonifying the kidney,tonifying Qi,invigorate the circulation of blood and others that is of great importance to discover traditional Chinese medicine to treat the cadmium induced damage.The Polygonatum Sibiricum has efficiency of boosting Qi and nourishing Yin and tonifying the kidney,and has a good clinical effect for asthenia of essence and blood,soreness of the waist and the knees and others,especially.However,the treatment effect and mechanism of Polygonatum Sibiricum for injury of the cadmium-induced kidney is not clear.Therefore,the renal function indicates,the renal histopathological,the kidney metal metabolism and the level of molecular biology were studyed to explore the clinical effect and mechanism of Polygonatum Sibiricum on cadmium-induced kidney injury in mice.It can provide experimental reference for clinical application of anti-cadmium-injury by Polygonatum Sibiricum.In this study,we were selected the Polygonatum Sibiricum as the best anti-cadmium-injury from Polygonatum Sibiricum,Angelica Ssinensis,Fructus Corni,Rhizome of Rehmannia and Cistanche Salsa.Then we were detected the serum creatinine,urea nitrogen and uric acid to study the effect of Polygonatum Sibiricum on the kidney fuction in cadmium-induced mice,and the methods of histopathological slide was used to investigate the histopathological effect of Polygonatum Sibiricum on the kidney fuction in cadmium-induced mice,and the metal metabolism of cadmium,zinc,copper,iron and manganese was detected by atomic absorption spectrophotometry in the cadmium induced kidney injury after treatment by Polygonatum sibiricum,and at the last,the expression level of P53,Bcl-xl,Bcl-2,Bax and Caspase 3 mRNA were checked by RT-PCR in the cadmium induced kidney injury after treatment by Polygonatum Sibiricum.Result as follows:(1)Screening of traditional Chinese medicine for treatment of cadmium induced kidney injury in miceThe content of serum creatinine and urea nitrogen and reral cadmium in model group had significantly increase compared with the control group(P<0.05),and serum uric acid had significantly decrease compared with the control group(P<0.05).Polygonatum Sibiricum,Angelica Sinensis,Fructus Corni,Rhizome of Rehmannia and Cistanche Salsa can significantly increase the content of serum uric acid in cadmium induced mice compared with the model group(P<0.05);Polygonatum Sibiricum,Angelica Sinensis and Rhizome of Rehmannia can significantly reduce the content of serum creatinine and urea nitrogen in cadmium induced mice compared with the model group(P<0.05);Polygonatum Sibiricum,Angelica Sinensis,Rhizome of Rehmannia and Cistanche Salsa can significantly reduce the content of cadmium in kidney which induced cadmium(P<0.05),and Polygonatum Sibiricum makes the content of cadmium in kidney decreased by 43.48%,and the Angelica Sinensis,Rhizome of Rehmannia and Cistanche Salsa were 34.95%,24.36% and 24.74%,respectively;In the model group,the renal tubular epithelial cells were swollen and necrotic,the intercellular space became larger,and the clearance between glomeruli and renal capsule disappeared.Compared to the model group,the treatment groups have a clearly nucleus image,and the decreasing swelling cell,and the clearly gap between the tubular lumen,the normally structure of glomerulus and renal capsule.(2)Effect of Polygonatum Sibiricum on kidney function after injuryed by cadmiumThe content of serum creatinine and urea nitrogen in model group had significantly increase compared with the control group(P<0.05),and serum uric acid had significantly decrease compared with the control group(P<0.05).The content of serum creatinine and urea nitrogen of Polygonatum Sibiricum treatment group was significantly lower than that of model group in the treatment of 15 d,25d,35d(P<0.05),and the content of serum creatinine and urea nitrogen in low dose group of Polygonatum Sibiricum was significantly higher than medium and high dose group,and the high dose group was significantly higher than medium dose group;The treatment group were also significantly recovery with serum uric acid level in cadmium induced mice(P<0.05),and it has time-and dose-dependent.(3)Effect of Polygonatum Sibiricum on the content of metal elements after injuryed by cadmiumThe content of reral cadmium in model group had significantly increase compared with the control group(P<0.05),and cadmium content in the kidney was increased with the prolongation of time,and its copper,manganese and iron had significantly decrease compared with the model group(P<0.05).In the treatment of 15 d,the renal cadmium content of the Polygonatum Sibiricum treatment group was significantly higher than the model group(P<0.05).In the treatment of 25 d,the renal cadmium content of the Polygonatum Sibiricum treatment group had no significantly difference compared with the model group(P>0.05).In the treatment of 35 d,the the renal cadmium content of the Polygonatum Sibiricum treatment group were significantly lower than model group(P<0.05),and the medium dose group of Polygonatum Sibiricum was significantly reduced among the three dose group,the renal cadmium content was decreased about 54%.The Polygonatum Sibiricum had no significant effect the renal zinc content in the cadmium induced mice at 15 and 25 days after treatment comparied with the model group(P>0.05),however,in the treatment of 35 d,the renal zinc content of treatment group was significantly increased compared with control group and model group(P<0.05).In the whole treatment cycle,Polygonatum Sibiricum can effectively restore the renal iron and copper content in the cadmium induced mice,comparied with the model group(P<0.05).In 15 d after treatment of Polygonatum Sibiricum on cadmium induced kidney injury,the renal manganese content had not significantly changed(P>0.05),but the renal manganese content can significantly recoveried in cadmium induced kidney injury at 25 and 35 days after treatment in the treatment of medium-term and post-treatment stage(P<0.05).(4)Effect of Polygonatum Sibiricum on renal histopathological after injuryed by cadmiumIn the model group,the renal tubular epithelial cells were swollen and necrotic,the intercellular space became larger,and the clearance between glomeruli and renal capsule disappeared.In the treatment of 15 d,the lumen of renal tubular is not obvious in low dose group and medium dose group,however,the lumen of renal tubular was clearly visible in high dose group.After the treatment of 25 d,the tubulars of renal lumen in each treatment group were clearly visible.After treatment,the glomerular structure of each group tends to be normal with the extension the treatment time.(5)Effect of Polygonatum Sibiricum on renal gene expression after injuryed by cadmiumAfter mice exposed by cadmium,the anti-apoptotic gene expression level of bcl-2?Bcl-xl mRNA was significantly down-regulated(P<0.05),and the pro-apoptotic gene P53,Bax and Caspase 3 mRNA was significantly up-regulated(P<0.05),compared with contol group in kidney,and it had time dependent.After treatment with Polygonatum Sibiricum,the anti-apoptotic gene expression of Bcl-xl and Bcl-2 mRNA of each treatment group were significantly up-regulated(P<0.05),and pro-apoptotic gene expression of P53,Bax and Caspase 3 mRNA were significantly down-regulated(P<0.05),compared with model group in kidney.And the medium dose group of Polygonatum Sibiricum is best recovery for P53-Bcl-2-Caspase 3 pathway mRNA expression.Conclusions: Polygonatum Sibiricum has obvious effect in the recovery of renal function,reduce renal cadmium content,histological recovery and etc.Besides,the Polygonatum Sibiricum can also regulate the metabolic balance of metal elements in the mice exposed by cadmium,and up-regulate anti-apoptosis gene expression of Bcl-2 and Bcl-xl mRNA,and down-regulate pro-apoptotic gene expression of P53,Bax and Caspase 3 mRNA to make its resistance to cadmium induced kidney injury. |
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