丝裂原活化蛋白激酶(MAPK)途径的活化诱导响应于炎症刺激的不受控制的细胞增殖。阿霉素(ADR)诱导的肾病(ADRN)大鼠通过增加细胞因子分泌触发MAPK激活和促炎机制,与慢性肾脏病(CKD)相似。维生素D受体(VDR)的激活在抑制肾脏中炎性标志物的表达中起着至关重要的作用,并可能有助于减少细胞增殖。这项研究评估了帕立骨化醇预处理对肾脏炎症机制中ADRN的影响。
■雄性Sprague-Dawley大鼠植入含有活化维生素D(帕立骨化醇,圣殿,6ng/天)或媒介物(NaCl0.9%)。植入后两天,ADR(Fauldoxo,注射3.5mg/kg)或媒介物(NaCl0.9%)。将大鼠分为四个实验组:对照组,n=6;帕立骨化醇,n=6;ADR,n=7,ADR+帕立骨化醇,n=7。
■肾组织中CYP24A1的增加证明了VDR的激活。帕立骨化醇可防止肾小球中的巨噬细胞浸润,皮质,和外髓质,阻止肿瘤坏死因子-α的分泌,白细胞介素-1β,增加的精氨酸酶I和减少的精氨酸酶II组织表达,与MAPK通路衰减相关的效应,增加小带闭塞1,并减少与增殖细胞核抗原表达相关的细胞增殖。帕立骨化醇治疗降低了基质细胞衍生因子1α/趋化因子C-X-C受体4型/β-catenin途径。
■帕立骨化醇通过调节肾脏炎症和细胞增殖发挥肾脏保护作用。这些结果突出了治疗CKD的潜在靶标。
UNASSIGNED: Activation of the mitogen-activated protein kinase (MAPK) pathway induces uncontrolled cell proliferation in response to inflammatory stimuli. Adriamycin (ADR)-induced nephropathy (ADRN) in rats triggers MAPK activation and pro-inflammatory mechanisms by increasing cytokine secretion, similar to chronic kidney disease (CKD). Activation of the vitamin D receptor (VDR) plays a crucial role in suppressing the expression of inflammatory markers in the kidney and may contribute to reducing cellular proliferation. This study evaluated the effect of pre-treatment with paricalcitol on ADRN in renal inflammation mechanisms.
UNASSIGNED: Male Sprague-Dawley rats were implanted with an osmotic minipump containing activated vitamin D (paricalcitol, Zemplar, 6 ng/day) or vehicle (NaCl 0.9%). Two days after implantation, ADR (Fauldoxo, 3.5 mg/kg) or vehicle (NaCl 0.9%) was injected. The rats were divided into four experimental groups: control, n = 6; paricalcitol, n = 6; ADR, n = 7 and, ADR + paricalcitol, n = 7.
UNASSIGNED: VDR activation was demonstrated by increased CYP24A1 in renal tissue. Paricalcitol prevented macrophage infiltration in the glomeruli, cortex, and outer medulla, prevented secretion of tumor necrosis factor-α, and interleukin-1β, increased arginase I and decreased arginase II tissue expressions, effects associated with attenuation of MAPK pathways, increased zonula occludens-1, and reduced cell proliferation associated with proliferating cell nuclear antigen expression. Paricalcitol treatment decreased the stromal cell-derived factor 1α/chemokine C-X-C receptor type 4/β-catenin pathway.
UNASSIGNED: Paricalcitol plays a renoprotective role by modulating renal inflammation and cell proliferation. These results highlight potential targets for treating CKD.