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Objective To explore the effects and mechanisms of losartan on atheroscleorsis and T cell (Treg/Th17) immune balance of CKD apolipoprotein E knockout (ApoE-/-) mice.Methods The model of CKD was induced by a 5/6 nephrectomy (SNx) in male ApoE-/-mice.ApoE-/-mice were randomly allocated into 3 subgroups:the control group,SNx group and losartan group.The fifth week after building model the mice in losartan group were taken losartan at a dose of 30 mg/(kg · d) by intragastric administration for 12 weeks.While the other mice were treated with the same volume of 0.5％ sodium carboxymethylcellulose.Sixteen weeks after nephrectomy,the serum levels of urea and creatinine were determined.Haematoxylin Eosin (HE) staining were used to observe the general morphology changes of atherosclerotic plaque.Flow cytometry was performed to detect the proportion of T cells (Treg/Th17) in spleen.Enzyme linked immunosorbent assay (ELISA) was performed to detect the level of cytokines in serum such as interleukin (IL)-17,IL-6,transforming growth factor-β1 (TGF-β1) and IL-10.Results Sixteen weeks after nephrectomy,the result of serum creatinine and urea nitrogen showed the CKD animal model established successfully.Losartan could improved the renal function of CKD mice.The size of aortic root plaques in control group,SNx group,and losartan group are (16.35 ± 3.72) × 104 μm2,(28.64 ± 5.86) × 104 μm2 and (22.76 ± 3.97) × 104 μ m2 respectively,indicating that losartan treatment significantly decreased the size of aortic root plaques of the CKD mice (P ＜ 0.05).The proportion of Treg cells in the spleen of control group,SNx group,and losartan group are (4.34 ± 0.93) ％,(1.78 ± 0.56) ％,and (2.68 ± 0.58)％ respectively,indicating that losartan treatment significantly increased the proportion of Treg cells of CKD mice (P ＜ 0.01).The proportion of Th17 cells in the spleen of control group,SNx group,and losartan group are (0.11 ± 0.06) ％,(0.67 ± 0.12) ％,(0.37 ± 0.08) ％ respectively,indicating that losartan treatment significantly decreased the proportion of Th17 cells of CKD mice (P ＜ 0.01).Compared with control mice,the level of cytokines TGF-β1 and IL-10 in the serum of the SNx group mice significantly decreased (P ＜0.01),and the level of cytokines IL-17 and IL-6 in the serum of the SNx group mice significantly increased (P ＜0.01),indicating that such effects could be significantly regulated by losartan (P ＜ 0.05).Conclusions Losartan inhibited the differentiation of Th17 cell subsets,promoted the differentiation of Treg,and alleviated atherosclerosis in CKD ApoE-/-mice by modulating the immune imbalance of the Treg/Th17 cell.
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Objective To observe the efficacy and safety of prednisone combined with leflunomide in the treatment of immu-noglobulin A(IgA)nephropathy.Methods Eighty patients with IgA nephropathy were selected and divided into the treatment group and control group.The patients in the control group were given prednisone and the treatment group received prednisone plus leflunomide.The treatment course lasted for 12 months.Total effective rate,serum creatinine(Scr),urinary protease inhibitor C(Cys C),blood urea nitrogen(BUN)and 24 h proteinuria(U-prot)were measured at 6-month and 12-month treatment.Serum levels of vascular endothelial growth factor(VEGF)and endothelin-1(ET-1)were measured by enzyme-linked immunosorbent assay (ELISA).Results The effective rates at 6-month and 12-month treatment in the treatment group were 85% and 90% respective-ly,which in the control group were 65% and 70% respectively,the difference between the two groups was statistically significant (P<0.05).The BUN and U-prot levels after 6-moth and 12-month treatment were significantly reduced,moreover the effect in the treatment group was better than that in the control group(P<0.05).The levels of plasma VEGF and ET-1 after 6-moth and 12-month treatment in the two groups were decreased,moreover the decrease range in the treatment group was greater than that in the control group(P<0.05).Conclusion Prednisone combined with leflunomide can significantly improve the renal function in the pa-tients with IgA nephropathy,and it is safe and effective.