氢氧化镧与慢性肾脏病-矿物质和骨代谢紊乱：大鼠模型。

Lanthanum Hydroxide and Chronic Kidney Disease Mineral and Bone Disorder: A Rat Model.

机构信息

Department of Pharmacy, Ordos City Hospital, Dongsheng District, Ordos City, 017000, Inner Mongolia Autonomous Region, China.

Department of Pharmacology, College of Pharmacy, the Inner Mongolian Medical University, Jinshan Development, Hohhot, 010110, Inner Mongolia Autonomous Region, China.

出版信息

Curr Vasc Pharmacol. 2024;22(2):122-136. doi: 10.2174/0115701611254269231105063028.

DOI:10.2174/0115701611254269231105063028

PMID:37961858

Abstract

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. LH 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.

摘要

目的

研究氢氧化镧（LH）对急性肾损伤（AKI）大鼠软组织异位矿化和异常骨形成的药理作用及分子机制。

方法

通过 5/6 肾切除术建立 Wistar 大鼠模型。手术后，将大鼠分为不同组，在不同时间采集血清生化指标。通过灌胃分别给予 LH0.4、0.2 和 0.1g/kg 剂量，在 LH 治疗 16 周后处死大鼠。通过特异性染色观察组织病理变化。采用 Western Blot、实时定量 PCR 和免疫组织化学技术检测对相关通路蛋白的影响。

结果

与对照组（未给予 LH）相比，LH 组血清磷酸盐水平明显降低（p<0.01），胸主动脉钙化减少（p<0.05，p<0.01）（给药前和药物治疗周期内的血清生化检测），肾纤维化改善（p<0.01），核因子 kappa-B（NF-κB）核内进入减少（p<0.01），平滑肌蛋白 22α（SM22α）表达明显增加（p<0.01）。成骨标记基因的表达减少。此外，与对照组相比，模型组股骨中核因子受体激活剂配体/骨保护素（RANKL/OPG）比值增加（p<0.05）。