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冻干小牛骨髓水解物脂质体粉末改善肾性贫血：体内外评价

Lyophilized powder of calf bone marrow hydrolysate liposomes improved renal anemia: In vitro and in vivo evaluation.

作者信息

Li Li, Zhao Shasha, Liu Xiaodun, Xu Zhe, Li Dong, Dai Xiaoyu

机构信息

Department of Research and Development, Jinan Perfect Biological Technology Co., LTD, Jinan, Shandong, China.

出版信息

PLoS One. 2024 Dec 26;19(12):e0314811. doi: 10.1371/journal.pone.0314811. eCollection 2024.

DOI:10.1371/journal.pone.0314811
PMID:39724079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11670988/
Abstract

This study aimed to find whether oral administration of calf bone marrow hydrolysate liposomes (CBMHL) can improve renal anemia. Calf bone marrow was defatted, papain hydrolyzed, liposomalized and lyophilized. Its hematopoietic ability was proved by the colony formation experiment of umbilical cord blood hematopoietic stem cells in vitro. The rat model of renal anemia was established by adenine intragastric administration, and different concentrations of CBMHL were intragastricly administrated. Blood routine and serological indexes, transcription levels of hematopoietic factors and renal pathology were detected. From the appearance, redispersability, water content, liposome indexes and stability of Lyophilized powder of CBMHL, it could be concluded that the quality of freeze-dried CBMHL powder under this freeze-drying process was good. Compared with the control group, the burst forming unit-erythroid (BFU-E) in the CBMHL group was larger and the number of colonies increased significantly in the colony formation experiment (P < 0.05). The results of lyophilized powder of CBMHL co-culture with human adipose mesenchymal stem cells (MSCs) and human cytokine-induced killer (CIK) cells showed that the lyophilized powder of CBMHL had no potential toxicity and allergic reaction in vitro. Compared with the Model Group, the red blood cell (RBC) count, hemoglobin (HB) content and hematokrit (HCT) of rats blood routine in the Model+high doses of CBMHL Group (Model+H-CBMHL Group) increased significantly (P < 0.05). Serum erythropoietin (EPO) and glutathione (GSH) levels increased significantly (P < 0.05), while serum creatinine (Cr) levels decreased significantly(P < 0.05). The transcription level of Epo in kidney increased significantly (P < 0.05), the transcription levels of erythropoietin receptor (Epor) in bone marrow and interleukin 6 (Il6) in spleen were significantly increased (P < 0.01). The fragility of red blood cells decreased significantly, and the pathological structure of kidney improved significantly. It was proved that lyophilized powder of CBMHL could effectively enhance the hematopoietic ability of rats with renal anemia and protect the kidney structure and function.

摘要

本研究旨在探究口服小牛骨髓水解物脂质体（CBMHL）是否能改善肾性贫血。小牛骨髓经脱脂、木瓜蛋白酶水解、脂质体化及冻干处理。通过体外脐血造血干细胞集落形成实验证实其造血能力。采用腺嘌呤灌胃建立肾性贫血大鼠模型，并灌胃不同浓度的CBMHL。检测血常规及血清学指标、造血因子转录水平和肾脏病理学变化。从CBMHL冻干粉的外观、再分散性、含水量、脂质体指标及稳定性来看，可得出在此冻干工艺下CBMHL冻干粉质量良好。在集落形成实验中，与对照组相比，CBMHL组的红系爆式集落形成单位（BFU-E）更大，集落数量显著增加（P<0.05）。CBMHL冻干粉与人脂肪间充质干细胞（MSCs）和人细胞因子诱导杀伤细胞（CIK）共培养结果表明，CBMHL冻干粉在体外无潜在毒性及过敏反应。与模型组相比，模型+高剂量CBMHL组（Model+H-CBMHL组）大鼠血常规中的红细胞（RBC）计数、血红蛋白（HB）含量及血细胞比容（HCT）显著升高（P<0.05）。血清促红细胞生成素（EPO）和谷胱甘肽（GSH）水平显著升高（P<0.05），而血清肌酐（Cr）水平显著降低（P<0.05）。肾脏中Epo的转录水平显著升高（P<0.05），骨髓中促红细胞生成素受体（Epor）和脾脏中白细胞介素6（Il6）的转录水平显著升高（P<0.01）。红细胞脆性显著降低，肾脏病理结构明显改善。证明CBMHL冻干粉能有效增强肾性贫血大鼠的造血能力，保护肾脏结构和功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/73b2243aac0c/pone.0314811.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/49b4ca969d1d/pone.0314811.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/e8f54b72d37f/pone.0314811.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/646c69cba463/pone.0314811.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/e6f1c03d84bb/pone.0314811.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/55257aca5c78/pone.0314811.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/e354961e4775/pone.0314811.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/d8d58b98ef72/pone.0314811.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/73b2243aac0c/pone.0314811.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/49b4ca969d1d/pone.0314811.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/e8f54b72d37f/pone.0314811.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/646c69cba463/pone.0314811.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/e6f1c03d84bb/pone.0314811.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/55257aca5c78/pone.0314811.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/e354961e4775/pone.0314811.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/d8d58b98ef72/pone.0314811.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/af5c/11670988/73b2243aac0c/pone.0314811.g008.jpg

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Lyophilized powder of calf bone marrow hydrolysate liposomes improved renal anemia: In vitro and in vivo evaluation.

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本文引用的文献

[1]
Nephroprotective effect of pioglitazone in a Wistar rat model of adenine‑induced chronic kidney disease.

Exp Ther Med. 2024-8-7

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Adv Exp Med Biol. 2023

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Antioxidants (Basel). 2023-11-1

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BMC Immunol. 2023-9-1

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2,8-Dihydroxyadenine-induced nephropathy causes hexosylceramide accumulation with increased mTOR signaling, reduced levels of protective SirT3 expression and impaired renal mitochondrial function.

Biochim Biophys Acta Mol Basis Dis. 2024-1

[10]
Renal anemia: current treatments and emerging molecules.

Rev Clin Esp (Barc). 2023

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