ABSTRACT
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.
ABSTRACT
Objective To investigate the alterations of peripheral blood T lymphocyte subsets in patients with sepsis and septic acute kidney injury, and explore the clinical significance.Methods Fifty-five patients with sepsis and forty-three patients with septic acute kidney injury were enrolled in this study. At the same period, thirty healthy subjects were enrolled as the control group.T lymphocyte subsets inclu-ding CD3 +T, CD4 +T, CD8 +T cells, and CD4 +T/CD8 +T in peripheral blood were detected by flow cy-tometry, and acute physiology and chronic health evaluation Ⅱ( APACHE Ⅱ) were graded within twenty-four hours after admission.Then, correlation of the APACHEⅡscores and T lymphocyte subsets was ana-lyzed.Results In the septic acute kidney injury group, peripheral blood CD3 +T, CD4 +T cell percenta-ges, and CD4 +T/CD8 +T ratio were significantly lower than those in the control group and the sepsis group (all P <0.05).In the septic acute kidney injury group with stage 3, CD3+T, CD4 +T cell percentages, and CD4 +T/CD8 +T ratio in the patients were significantly lower than those in stage 1 and stage 2 ( all P <0.05).In the septic acute kidney injury group,CD3 +T, CD4 +T cell percentages, and CD4 +T/CD8 +T ra-tio were significantly lower in dead group than those in survival group (all P <0.05).APACHEⅡscores in patients with sepsis were significantly negatively correlated with peripheral blood CD4 +T cell percentages and CD4 +T/CD8 +T ratio ( r =-0.645,-0.492, allP <0.05).Conclusions There are varying de-grees of cellular immune imbalance in patients with sepsis and septic acute kidney injury, characterized by decline of circulating CD3 +T, CD4 +T cell percentages, and CD4 +T/CD8 +T ratio.CD4 +T cell percenta-ges and CD4 +T/CD8 +T ratio are closely related to the severity and prognosis of septic acute kidney injury.