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Objective To explore the regulatory effect of TAK 1 inhibitors on MAPK and NF-κB signaling pathway in diabetic rats and its renal protection mechanism .Methods A total of 48 rats accorded to the random number table method were divided into DN group , TAK1 group and control group ,each group with 16 rats,control group with normal fed , DN group and TAK1 group by the intraperitoneal injection of 1%50 mg/kg STZ DN model rat.8 rats were killed in each group at 4 weeks and 8 weeks respectively ,the pathological changes of renal tissue were observed ,serum TNF-α,MCP-1,IL-1βlevels were detected by enzyme linked immunosorbent assay ,p38MAPK,NF-κBp63 protein expression were detected by Western blotting ,p38MAPK、NF-κBp63 mRNA levels in renal tissue were detected by real time fluorescence quantitative PCR.Results At 4 weeks and 8 weeks, the body weight, blood glucose and UAER of DN group and TAKl group were significantly higher than those in control group (P <0.05).The body weight and UAER of DN group were significantly higher than those of TAK1 group (P <0.05).The serum TNF-α,MCP-1,IL-1βlevels in DN group and TAK1 group were significantly higher than those in control group (P <0.05),and DN group serum TNF-α,MCP-1,IL-1βlevels were significantly higher than those in TAK1 group (P <0.05).The expression levels of p38MAPK,NF-κBp63 protein and mRNA in DN group, TAK1 group were significantly higher than those in control group (P <0.05), and p38MAPK,NF-κBp63 protein and mRNA in DN group was significantly higher than that in TAK 1 group ( P <0.05 ) .Conclusions TAK1 induces inflammation by activating MAPK and NF-κB signaling pathways,and participates in diabetic renal injury . TAK1 inhibitors with anti-inflammatory effect by down regulate the expression of inflammatory factors .
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OBJECTIVE:To compare therapeutic efficacies of Shengxuening tablet and Iron sucrose injection for anemia in maintenance hemodialysis(MHD)patients,and their effects on oxidative stress and micro-inflammation state. METHODS:80 pa-tients who had received MHD over half year were assigned into shengxuening group and iron sucrose group with 40 cases in each group. Both groups received MHD 3 times a week,4 h/time,blood flow of 200~300 ml/min;erythropoietin(EPO)was used at a dose of 10 000 IU/time hypodermically in each group. Shengxuening group was additionally given Shengxuening tablet orally,0.5 g/time,tid. Iron sucrose group was given Iron sucrose injection 100 mg 2 h intravenously via dialyser after the beginning of hemo-dialysis,twice a week,received iron treatment every one week until complete the total dose of 1 000 mg,to maintain ferritin be-tween 100~300 μg/L. The levels of Hb,Hct,SF,TSAT,hs-CRP,IL-6,TNF-α,MDA,SOD and GSH-Px were tested in 2 groups before and 12 weeks after the treatment. RESULTS:After 12 weeks of treatment,the levels of Hb,Hct,SF and TSAT in 2 groups were significantly increased,with statistical significance (P0.05). Compared with before treatment,the levels of hs-CRP,IL-6,TNF-α and MDA increased significantly in iron sucrose group,while SOD and GSH-Px levels declined significantly,with statistical significance (P<0.01). Above indicators of shengxuening group had no significant change,compared with before treatment;there was statistical significance between 2 groups after treatment(P<0.01). No obvious ADR was found in 2 groups. CONCLUSIONS:Therapeutic efficacy of shengxuening is simi-lar to that of iron sucrose in improving the anemia and iron deficiency status of MHD patients,but doesn't aggravate oxidative stress and micro-inflammation state. It is an safe and effective oral iron supplement drugs.
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A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation group (Sham, n = 25), Uninephrectomy group (UPHT, n = 25) and Uninephrectomy+Daunorubicin group (DRB, n = 30). In DRB group, daunorubicin (5 mg/kg) was injected via tail vein on the 7th and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively following establishment of the animal model, 5 rats in Sham group and UPHT group, and 6 in DRB group were taken respectively for determining 24-h urinary protein excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr). The sections of kidneys were examined by an electric microscope, PAS staining, immunohistochemical staining and in situ hybridization histochemistry. The results showed that 24hUPER, BUN and Scr in DRB group were more than those in Sham group and UPHT group at the same time points, and there was a trend towards an increase on level of GSI in DRB group from week 2 to week 8. Electric microscopy revealed that podocyte injury presented in DRB group. The expression of Ang1 mRNA and protein in glomeruli of DRB group was decreased, while the expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the expression of Ang1 mRNA had a negative correlation with the expression of Ang2 mRNA, and the expression of Ang1 protein had a positive correlation with the expression of Ang1 mRNA, and had a negative correlation with 24hUPER, BUN, Scr, glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV protein. The expression of Ang2 protein had a positive correlation with the expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr, GSI, the expression of CoIV protein. It was concluded that podocyte injury might lead to an alteration in the expression of Ang1 and Ang2 within glomeruli. Ang2 may get rid of inhibition from Ang1 for downregulation of the Ang1 expression, which facilitate upregulation of the Ang2 expression in glomeruli to promote progressive glomerulosclerosis in the rats.
ABSTRACT
A potential pathological role of angiopoietins (Ang) in glomeruli following podocyte injury-induced progressive glomerulosclerosis was explored. Eighty male Wistar rats were randomly allocated into sham operation group (Sham, n = 25), Uninephrectomy group (UPHT, n = 25) and Uninephrectomy+Daunorubicin group (DRB, n= 30). In DRB group, daunorubicin (5 mg/kg)was injected via tail vein on the 7th and 14th day after uninephrectomy. At week 1, 2, 4, 6 and 8 respectively following establishment of the animal model, 5 rats in Sham group and UPHT group,and 6 in DRB group were taken respectively for determining 24-h urinary protein excretion rate (24hUPER), blood urea nitrogen (BUN) and serum creatinine (Scr). The sections of kidneys were examined by an electric microscope, PAS staining, immunohistochemical staining and in situ hybridization histochemistry. The results showed that 24hUPER, BUN and Scr in DRB group were more than those in Sham group and UPHT group at the same time points, and there was a trend towards an increase on level of GSI in DRB group from week 2 to week 8. Electric microscopy revealed that podocyte injury presented in DRB group. The expression of Ang1 mRNA and protein in glomeruli of DRB group was decreased, while the expression of Ang2 protein in glomeruli of DRB group increased. Meanwhile, the expression of Angl mRNA had a negative correlation with the expression of Ang2 mRNA, and the expression of Angl protein had a positive correlation with the expression of Angl mRNA, and had a negative correlation with 24hUPER, BUN, Scr, glomerular sclerotic index (GSI), the expression of Ang2 protein and CoIV protein. The expression of Ang2 protein had a positive correlation with the expression of Ang2 mRNA, and had a positive correlation with 24hUPER, BUN, Scr, GSI, the expression of CoIV protein. It was concluded that podocyte injury might lead to an alteration in the expression of Angl and Ang2 within glomeruli. Ang2 may get rid of inhibition from Ang1 for downregulation of the Angl expression, which facilitate upregulation of the Ang2 expression in glomeruli to promote progressive glomerulosclerosis in the rats.
ABSTRACT
AIM:To study the potential pathological role of abnormal expression of endogenous angiopoietins in progressive glomerulosclerosis.METHODS:80 male Wistar rats were randomly allocated into sham operation group(sham,n=25),unilateral nephrectomy group(UNx,n=25)and UNx+daunorubicin(DRB)group(n=30).The rats in DRB group were intravenously injected with DRB(5 mg/kg)on the seventh and the fourteenth day respectively after excising one kidney.Then,at week 1,2,4,6 and 8,5,male Wistar rats from each group were taken randomly for determining 24 h urinary protein quantitative measurement(24hUPQ),BUN,Scr,and the kidneys were examined by electronic microscope,PAS staining,immunohistochemical staining and in situ hybridization histochemistry.RESULTS:There was a trend towards an increase respectively in levels of 24hUPQ,Bun,Scr,GSI in DRB from week 2 to week 8.Electronic microscope revealed that podocyte injury presented in DRB group.Expression of Ang1 mRNA and protein in glomerulus in DRB group decreased,while expression of Ang2 protein in glomeruli in DRB group increased.In DRB group,expression of Ang1 protein had a negative correlation with 24hUPQ,BUN,Scr,GSI,expression of Ang2 protein and CoIV protein.Expression of Ang2 protein had a positive correlation with 24hUPQ,BUN,Scr,GSI,expression of CoIV protein.CONCLUSION:Podocyte injury may lead to glomeruli abnormally express angiopoietins.A decrease in expression of Ang1,and upregulation in expression of Ang2 may facilitate progressive glomerulosclerosis in the rat.