| Renal function was progressive deterioration in normal aging process.Histologically test found that the kidney of seniors and aging rats appeared focal segmental glomerular sclerosis and decreased in the number of glomeruli.Morphological changes including age-related mesangial matrix expansion and glomerular diameter increases,basement membrane thickening and capillary circulation loss.Age-related cause of glomerular disease is multiple factors,including the extracellular matrix of unbalance between synthesis and degradation products,as well as the hemodynamic changes.In recent years,according to a study by aging in various tissues is closely related to oxidative stress increase.Nuclear factor E2 related factor 2(Nrf2)can regulate gene induced antioxidation reaction component,widely recognised as a major cell oxidation stress defense mechanism.Activation of Nrf2-ARE way might be in the body has a protective effect.However,TP have protective effect to aging kidney cells by activating Nrf2-ARE signal pathway which is not clear.Objective: To explore the effects of long-term TP treatment on aging rat kidney function and oxidative stress state,as well as the mechanism of Nrf2-ARE signal pathway involved in antioxidant process.Methods: Male Wistar rats were randomly divided into three groups.6 months of age group(6Mon,n=10),24 months of age group(24Mon,n=10)and 24 months of age following treatment with PTX group(24Mon-PTX,n=10).24Mon-PTX rats received intraperitoneal injection of PTX at the age of 21 months.The dosage was 50mg/kg(dissolved in 0.9% saline).Once a day.The supplement of PTX continued for 12 weeks(84-day).6Mon and 24 Mon rats received 0.9% saline at the same time.5 rats in each group were used for immunohistochemical analysis.The venous blood was collected for kidney function index determination by enzyme-linked immuno sorbent assay(ELISA)determination.Another 5 rats in each group were used for oxidative stress parameters assay,real-time fluorescence quantitative PCR and Western blot analysis.Results:1 Kidney function results:Compared with 6Mon rats,BUN,Cre,UA and β2MG were significantly increased(P<0.01)in 24 Mon rats.The above indicators were reduced significantly after long-term TP treatment(P<0.01),but not reached the levels of 6Mon rats(P<0.01).2 Oxidative stress parameters results:Compared with 6Mon rats,kidney malondialdehyde(MDA)and lipid peroxidation(LPO)levels were significantly increased(P<0.01),reduced glutathione(GSH),Glutathione peroxidase(GSH-px),catalase(CAT)and superoxide dismutase(SOD)levels were decreased significantly(P<0.01)in 24 Mon rats.MDA and LPO were significantly reduced(P<0.01),GSH,GSH-px,CAT and SOD levels were increased significantly(P<0.01)after long-term TP treatment,but not reached the levels of 6Mon rats(P<0.01).3 Real-time quantitative PCR detection results: Compared with 6Mon rats,kidney Nrf2 mRNA,HO-1 mRNA and NQO1 mRNA expression were significantly reduced(P<0.01)in 24 Mon rats.The above index expression were increased significantly after long-term TP treatment(P<0.01),but not reached the levels of 6Mon rats(P<0.01).4 Western blot test results: Compared with 6Mon rats,kidney Nrf2,HO-1 and NQO1 proteins expression were significantly reduced(P<0.01)in 24 Mon rats.The above index expression increased significantly after long-term TP treatment(P<0.01),but not reached the levels of 6Mon rats(P<0.01).5 Immunohistochemical detection results: Compared with 6Mon rats,the average optical density(AOD)of kidney NQO1 significantly reduced(P<0.01)in 24 Mon rats.The AOD of NQO1 increased significantly after long-term TP treatment(P<0.01),but not reached the levels of 6Mon rats(P<0.01).Conclusions: Long-term TP treatment activated the Nrf2-ARE antioxidant pathway,improve the state of oxidative stress in the aging kidney,and then improve the renal function.The results provided a theoretical basis for TP adjuvant treatment of kidney cell damage in aging process. |
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