Mechanism of regulatory T cells in heat stroke-induced acute kidney injury / 中华危重病急救医学

OBJECTIVE@#To investigate the mechanism of regulatory T cells (Treg) in heat stroke (HS)-induced acute kidney injury (AKI).@*METHODS@#Male SPF Balb/c mice were randomly divided into control group, HS group (HS+Rat IgG), HS+PC61 group, and HS+Treg group (n = 6). The HS mice model was established by making the body temperature of the mice reach 42.7 centigrade at room temperature 39.5 centigrade with relative humidity 60% for 1 hour. In HS+PC61 group, 100 μg PC61 antibody (anti-CD25) was injected through the tail vein in consecutive 2 days before the model was established to eliminate Tregs. Mice in HS+Treg group was injected with 1×106 Treg via tail vein immediately after successful modeling. The proportion of Treg infiltrated in the kidney, serum creatinine (SCr) and histopathology, levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) both in the serum and kidney tissue, as well as proportion of neutrophils and macrophages located in the kidney were observed at 24 hours after HS.@*RESULTS@#HS dampened renal function and exaggerated kidney injury, up-regulated levels of inflammatory cytokines both in local kidney and circulation, and increased infiltration of neutrophils and macrophages to the injured kidneys. The proportion of Treg (Treg/CD4+) infiltrated in kidney was significantly decreased in HS group, compared with control group [(3.40±0.46)% vs. (7.67±0.82)%, P < 0.01]. Compared with HS group, local Tregs in kidney were almost completely depleted via PC61 antibody [(0.77±0.12)% vs. (3.40±0.46)%, P < 0.01]. Depletion of Tregs could exacerbate HS-AKI, indicating by increased serum creatinine [SCr (mmol/L): 348.22±35.36 vs. 254.42±27.40, P < 0.01] and pathological injury (Paller score: 4.70±0.20 vs. 3.60±0.20, P < 0.01), incremental levels of IFN-γand TNF-α both in injured kidney and serum [serum IFN-γ (ng/L): 747.70±64.52 vs. 508.46±44.79, serum TNF-α (ng/L): 647.41±26.62 vs. 464.53±41.80, both P < 0.01], and more infiltrated neutrophils and macrophages in the injured kidney [neutrophil proportion: (6.63±0.67)% vs. (4.37±0.43)%, macrophage proportion: (38.70±1.66)% vs. (33.19±1.55)%, both P < 0.01]. On the contrast, adoptive transfer of Tregs could reverse the aforementioned effects of Treg depletion, indicating by incremental proportion of Tregs in the injured kidney [(10.58±1.19)% vs. (3.40±0.46)%, P < 0.01], decreased serum creatinine [SCr (mmol/L): 168.24±40.56 vs. 254.42±27.40, P < 0.01] and pathological injury (Paller score: 2.73±0.11 vs. 3.60±0.20, P < 0.01), reduced levels of IFN-γ and TNF-α both in injured kidney and serum [serum IFN-γ (ng/L): 262.62±22.68 vs. 508.46±44.79, serum TNF-α (ng/L): 206.41±22.58 vs. 464.53±41.80, both P < 0.01], and less infiltrated neutrophils and macrophages in the injured kidney [neutrophil proportion: (3.04±0.33)% vs. (4.37±0.43)%, macrophage proportion: (25.68±1.93)% vs. (33.19±1.55)%, both P < 0.01].@*CONCLUSIONS@#Treg might be involved in HS-AKI, possibly via down-regulation of pro-inflammatory cytokines and infiltration of inflammatory cells.

Study on Improvement Effect of Lanthanum Hydroxide on Chronic Renal Failure Hyperphosphatemia in Rats / 中国药房

OBJECTIVE:To study the improvement effect of lanthanum hydroxide on chronic renal failure (CRF) hyperphos-phatemia in rats. METHODS:CRF hyperphosphatemia rat model were induced and then randomly divided into model group,lan-thanum carbonate group [0.3 g/(kg·d)],calcium carbonate group [4.2 g/(kg·d)] and lanthanum hydroxide high-dose,medium-dose and low-dose groups [1.5,1,0.5 g/(kg·d)] with 10 rats in each group. They were given adenine 0.2 g/(kg·d)intragastrically in the morning,and then given relevant medicine intragastrically in the afternoon;a week later,they stopped taking adenine but con-tinued to take relevant medicine for 22 d. 10 normal rats were selected as normal control group. General examination was conduct-ed,and renal coefficient,serum contents of calcium,phosphorus,PTH,creatinine(Scr)and usea nitrogen(BUN)were detected after last medication as well as renal pathological change. RESULTS:Compared with normal control group,model group showed CRF sign,renal coefficient,the contents of phosphorus,PTH,Scr and BUN were increased,while the content of calcium was de-creased(P<0.01);renal section showed obvious pathological characteristics. Compared with model group,CRF sign of rats were improved in lanthanum carbonate group,calcium carbonate group and lanthanum hydroxide groups. The renal coefficient (except for lanthanum hydroxide high-dose group),serum contents of phosphorus(except for calcium carbonate group),PTH(except for lanthanum hydroxide low-dose group and calcium carbonate group),Scr(except for lanthanum hydroxide low-dose group and calci-um carbonate group)and BUN were all decreased,while serum content of calcium and calcium-phosphorucs product(only in calci-um carbonate group)was increased(P<0.05 or P<0.01). There was no statistical significance in other difference. The renal sec-tion pathological characteristics were improved. CONCLUSIONS:Lanthanum hydroxide can improve renal function and reduce the level of serum phosphorus in CRF hyperphosphatemia model rats.