骨保护素
医学
内科学
免疫印迹
内分泌学
肾
免疫组织化学
钙化
肾脏疾病
受体
激活剂(遗传学)
化学
生物化学
基因
作者
Chao Gu,Ting Zhang,Yuan Gao,Xiaojia Li,Xiaobin Yuan,Qiwen Wang,Hong Liu,Ruilan Han,Gang Li
出处
期刊:Current Vascular Pharmacology
[Bentham Science]
日期:2023-11-13
卷期号:21
标识
DOI:10.2174/0115701611254269231105063028
摘要
Objective: To investigate the pharmacological effects and molecular mechanisms of lanthanum hydroxide(LH) on ectopic mineralization of soft tissue and abnormal bone in rats with acute kidney injury(AKI). Methods: Wistar rats were modeled by 5/6 nephrectomy. After the operation, the rats were divided into different groups, the biochemical indexes of serum collected at different times. Lanthanum hydroxide was administered by intragastric tube at doses of 0.4, 0.2, and 0.1g/kg, respectively. Rats were sacrificed in the 16th week after LH treatment. Observation of pathological changes in tissues were made by specific staining. Western Blot, Real-Time Quantitative PCR, and immunohistochemistry techniques were used to detect the impact on pathway-related proteins. Results: Compared with the control group (no LH administered), the serum phosphate level of the LH group was significantly reduced (P<0.01), calcification of the thoracic aorta was reduced (P<0.05, P<0.01) (Serum biochemical tests before dosing and during drug treatment cycles), renal fibrosis was improved (P<0.01), nuclear entry of nuclear factor kappa-B (NF-κB) was reduced (P<0.01), and the expression of the smooth muscle protein 22α (SM22α) was significantly increased (P<0.01). The expression of osteogenic marker genes was decreased. In addition, compared with the controls, the receptor activator for nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio of the femur in the model group was increased (P<0.05) Conclusion: LH can inhibit the occurrence and development of vascular calcification and bone abnormalities in AKI rats by inhibiting the NF-κB and RANKL/OPG signaling pathways
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